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what do you call this
http://www.sequenom.com/Corporate/News.aspx
how is this for timing
29-Apr-09 Auriga U.S.A Initiated Buy sqnm
sequenom unbelievable
SAN DIEGO--(BUSINESS WIRE)--SEQUENOM, Inc. (NASDAQ: SQNM - News) announced today that the expected launch of its SEQureDx™ Down syndrome test is delayed, due to the discovery by company officials of employee mishandling of R&D test data and results. Accordingly the company is no longer relying on the previously announced R&D test data and results. SEQUENOM has not changed its plans to develop in parallel its RNA- and DNA-based methods for the Down syndrome test and will endeavor to have a validated test in the fourth quarter of 2009. Under the circumstances, and as supported by key clinical opinion leaders, the company now intends to launch the Down syndrome test upon publication in a peer-reviewed journal of the results from the on-going large, independent clinical studies, which are designed to be practice-changing for Down syndrome testing.
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SQNM 14.91 +0.53
{"s" : "sqnm","k" : "c10,l10,p20,t10","o" : "","j" : ""} The company’s board of directors has formed a special committee of independent directors to oversee an independent investigation of the employees’ activity related to the test data and results. The committee has engaged independent counsel to assist the committee in the conduct of the investigation.
Although the company is not aware of any potentially inappropriate activity related to the reported results of its other tests under development, the company is currently reviewing the data for all tests. As a result of this ongoing review the Rhesus D, Cystic Fibrosis and Fetalxy tests are now anticipated to begin launching in the third quarter of this year.
The company believes that its Down syndrome program has suffered a temporary setback but that the SEQureDx technology is scientifically and technically sound. The company intends to take every possible action to make up lost ground. SEQUENOM believes that it has the financial resources to commercialize its test for Down syndrome and other prenatal disorders.
Today’s announcement regarding the company’s SEQureDx Down syndrome R&D test data and results supersedes all previous announcements about such data and test, including its press releases dated June 4, 2008, September 23, 2008, December 1, 2008, January 28, 2009 and February 3, 2009.
SEQUENOM has scheduled a conference call for 2:00 p.m. Pacific time today at which Harry Stylli, PhD, SEQUENOM President and Chief Executive Officer, will discuss this announcement and along with other company officials will present information on the company’s operating results for the first quarter of fiscal 2009. A separate press release setting forth information on the company’s first quarter operating results will be issued prior to the call. Individuals interested in participating in the conference call may do so by dialing (866) 844-2998 for domestic callers or (706) 679-9912 for international callers. Those interested in listening to the conference call live via the Internet may do so by visiting the investor relations section of the company’s website at www.sequenom.com.
WRAPUP 9-WHO ready to warn of imminent pandemic
Wed Apr 29, 2009 3:55pm EDT
(For full coverage of the flu outbreak, click [nFLU])
so even the first swine flu death in the US is a mexican. Wonder what it is about mexicans that the virus doesn't like. I never heard of a redneck virus
* Virus in 9 countries, no sign outbreak slowing
* WHO expected to raise pandemic threat level shortly
* Mexican toddler is first U.S. fatality
* Markets wary, but impact thus far very limited (Adds economic impact, Mexico quote)
By Maggie Fox, Health and Science Editor
WASHINGTON, April 29 (Reuters) - The World Health Organization prepared to raise the pandemic threat level from swine flu to phase 5 on Wednesday as the virus spread and killed the first person outside Mexico, a toddler in Texas.
"Things are moving fast," a WHO source told Reuters.
Nearly a week after the H1N1 virus, or swine flu, first emerged in California and Texas and was found to have caused deaths in Mexico, Spain reported the first case in Europe of swine flu in a person who had not been to Mexico, illustrating the danger of person-to-person transmission.
Phase 5 is the WHO's second highest level of warning that a pandemic, or global outbreak of a serious new illness, is imminent.
"It is clear that the virus is spreading and we don't see evidence of it slowing down at this point," Dr. Keiji Fukuda, WHO acting assistant director-general, told a news briefing.
In Mexico, where up to 159 people have died from the virus and around 1,300 more are being tested for infection, people struggled with an emergency that has brought normal life virtually to a standstill.
"I'm depressed. I don't understand where this came from, how it spreads, how long it will last or what it will to the economy," an elderly woman named Licha said, sitting on a Mexico City park bench and wearing a surgical mask.
Germany and Austria reported cases, bringing the number of affected countries to 9. Fukuda said the WHO was moving closer to raising its pandemic alert to phase five, meaning a pandemic is imminent. Phase 6 means a pandemic has begun. [nLT649047]
U.S. officials said a 22-month-old boy had died in Texas -- the first confirmed U.S. swine flu death -- while on a family visit from Mexico.
Dr. Richard Besser, acting head of the U.S. Centers for Disease Control and Prevention, said the country now had 91 confirmed cases in 10 states from New York to California.
"We're going to find more cases. We're going to find more severe cases and I expect that we'll continue to see additional deaths," Besser said. [nN29385038]
President Barack Obama, who must manage the sudden flu emergency along with his broader drive to pull the United States out of its deep recession, said the Texas death showed it was time to take "utmost precautions" against the virus.[nLT884447].
MARKETS OVERCOME JITTERS
Despite jitters, many global markets rose as traders sought hopeful signs through the gloom of the worldwide financial crisis. [ID:nN29399582].
Airline shares, which had fallen on Monday and Tuesday, rallied on expectations that the outbreak may not significantly crimp travel demand [nN29408334] and U.S. pork futures recovered on the Chicago Mercantile Exchange as health officials hammered home the message that there was no danger posed by pigs or pork products. [ID:nN29411825]
"The market doesn't seem to be affected by this too much," said Cleveland Rueckert, market analyst at Birinyi Associates Inc. Stamford, Connecticut.
"Swine flu makes a good news story, but to be honest doesn't seem it's been as bad as some of the press has made it seem to be."
In some places, however, it was already bad. Mexico's central bank warned that the outbreak could push the country deeper into recession, hurting an economy that already shrank by as much as 8 percent in the first quarter. [ID:nN29421604]
France said it would seek a European Union ban on Thursday on flights to Mexico [nLT437502]. Argentina and Cuba have already stopped flights from Mexico.
The EU, the United States and Canada have advised against non-essential travel to the popular tourist destination, as nearly all the cases so far, in Canada, New Zealand, Israel and Spain, have been linked to travel from Mexico.
The WHO's Fukuda said the Spanish case -- involving a person who had reportedly been in contact with someone who visited Mexico but not traveled there themselves -- suggests the virus is spreading more easily among people.
"There are cases which are occurring in people who have not traveled," Fukuda told a briefing, saying the WHO was closer to raising its pandemic alert another notch [ID:nLT910095]
BIGGEST RISK SINCE 2003
H1N1 swine flu poses the biggest risk of a pandemic since H5N1 avian flu re-emerged in 2003, killing 257 people of 421 infected in 15 countries. In 1968 a "Hong Kong" flu pandemic killed about 1 million people globally, and a 1957 pandemic killed about 2 million.
The new strain contains genetic material from avian, swine and human viruses and appears to have evolved the ability to pass easily from one person to another.
It cannot be caught from eating pork products but Egypt ordered all its pigs to be slaughtered and some countries, led by Russia and China, have banned U.S. pork imports.
Obama's newly confirmed Health and Human Services Secretary Kathleen Sebelius held her first news conference on Wednesday seeking again to reassure the public
"We are determined to fight this outbreak and do everything we can to protect the health of every American," she said, adding that work also move speedily on a vaccine, although some experts said this could be tricky [ID:nN28309616]
The outbreak has deeply affected life in Mexico and ravaged tourism, a key earner. Mexico City was unusually quiet, with schools closed. Many parents took their children in to work.
All Mayan and Aztec pyramid ruins, dotted through central and southern Mexico, were closed until further notice.
Tourists and foreign students were hurrying to leave the country on Wednesday, fearing they could be stranded if the flu prompts officials to cut air links. [ID:nN29407032]
"We didn't want to get stuck here," said Alex Grinter, who left her Mexican beach vacation early to return to Australia.
Seasonal flu kills 250,000 to 500,000 people in a normal year, including healthy children in rich countries.
Health agencies advise frequent hand-washing and covering sneezes and coughs to help stop the spread. Experts generally agree that face masks, especially the surgical masks seen on the streets of Mexico City, offer little protection. (Reporting by Maggie Fox, Doina Chiacu and Will Dunham in Washington, Jason Lange, Catherine Bremer Alistair Bell and Helen Popper in Mexico City, Eric Burroughs and Tan Ee Lyn in Hong Kong; Writing by Andrew Quinn, editing by Anthony Boadle)
From Leerink Swann Positive REDUCE data expected to shadow ACAPODENE. The consultants commented that the proportion of men with the high grade-prostatic intraepithelial neoplasia (HG-PIN, targeted by ACAPODENE) is quite small in comparison to the suitable market for Avodart. While the REDUCE trial excluded men with preexisting HG-PIN, Avodart significantly reduced the new incidence of HG-PIN. Both consultants believe that even if ACAPODENE's cancer prevention trial is positive it would be hard to compete with Avodart. We also note that because of a similar magnitude of cancer risk reduction in the REDUCE (23%) as compared to the PCPT on Proscar (25%) and new data confirming lack of increase of more severe prostate cancer, positive REDUCE trial may increase the use of generic Proscar which would present an additional commercial hurdle for ACAPODENE.
Provenge manufacturing isn't to straight forward, I believe that is why they aren't filing until the fourth quarter.
under the best circumstances it will still be under review a year from now
Yes, indeed. Moreover, Proscar is already generic and it probably works as well as Avodart in cancer prevention (#msg-30016974).
I am taking generic proscar for this reason
bcrx...great work if you can find it
why are these guys worth so much
http://birmingham.bizjournals.com/birmingham/stories/2009/03/30/daily39.html?ana=yfcpc
BioCryst Inc. CEO Jon Stonehouse received a $122,000 raise in his total compensation in 2008, pushing his package to $1.6 million.
Stonehouse, who joined the Birmingham-based biotech firm in 2007, received $421,000 in base salary in 2008, up from $394,000 the year before. His total compensation for 2007 was $1.5 million. BioCryst has several drugs in the research phase and has never produced a commercial product since its founding in 1986.
Stonehouse, who resides in North Carolina, was granted options to purchase 100,000 shares of common stock as part of BioCryst’s special retention plan. He was offered 67,750 stock options as part of the firm’s long-term equity incentive program.
BioCryst Chief Financial Officer Stuart Grant was the company’s second-highest compensated employee receiving a package worth $942,000 in 2008 including a salary of $384,000.
Ground-Breaking Combination of All-Oral Agents Demonstrates Potential as Hepatitis C Treatment Regimen
On Saturday April 25, 2009, 12:30 pm EDT
slides
http://files.shareholder.com/downloads/VRUS/625252036x0x289832/6aed7c68-e17c-477c-aaeb-bfc43855460f/INFORM1_Slides.pdf
- Combination of R7227, protease inhibitor, and R7128, nucleoside polymerase inhibitor, shows significant potency in reducing viral load in patients with hepatitis C -
NUTLEY, N.J., BRISBANE, Calif., and PRINCETON, N.J., April 25 /PRNewswire-FirstCall/ -- Roche, InterMune, Inc. (Nasdaq: ITMN - News) and Pharmasset (Nasdaq: VRUS - News) today announced the first results from their innovative, interferon-free regimen of direct acting antiviral (DAA) combination therapy for the treatment of patients chronically infected with the hepatitis C virus (HCV)(1). The study combined two oral DAAs, R7227 (also known as ITMN-191) and R7128, for the first time in patients. There were no serious adverse events reported during the 14 days of dosing, and the reductions in levels of HCV RNA were significant.
Results of the INFORM-1 study were presented today during the late-breaker session at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL) in Copenhagen.
The trial, conducted in centers in New Zealand and Australia, is the first to investigate the combination of two oral antiviral medicines in the absence of interferon and ribavirin. The results demonstrated for the first time that the combination of an oral protease inhibitor and an oral nucleoside polymerase inhibitor resulted in significant HCV viral load reduction in patients with HCV. Roche is developing R7227, a protease inhibitor, with InterMune, and R7128, a nucleoside polymerase inhibitor, with Pharmasset.
Further studies will test the activity and safety of the combination of R7227 and R7128 with and without interferon and/or ribavirin. The current standard of care for HCV is a combination of pegylated interferon plus ribavirin, which delivers overall sustained virologic response rates (SVR) of 50-60 percent.
"These are exciting times in our fight against hepatitis C, and the investigation of the innovative oral treatment regimen in INFORM-1, if validated in further study, may radically change future treatment strategies in our patients with chronic HCV infection," said Edward Gane, M.D., Associate Professor, University of Auckland and Director, Auckland Clinical Studies Limited. "The initial results from this study of the R7227/R7128 combination raise hopes of the possibility for an interferon-free treatment regimen, as well as the potential for a shorter, more potent interferon-based regimen."
INFORM-1 Results in Brief
INFORM-1 is a randomized, double-blind, ascending dose Phase I trial which has enrolled a total of 57 patients.
Patients receiving the combination of R7227 and R7128 for 14 days -- without pegylated interferon or ribavirin -- experienced a median reduction in viral levels of -4.8 to -5.2 log(10) IU/mL in the highest doses tested. The addition of R7128 to R7227 resulted in sustained viral load reductions over the dosing period, with aproximately 63 percent of patients experiencing a decrease in viral levels below the quantification limit of the diagnostic assay (less than 40 IU/mL). Furthermore, 25 percent of patients in the highest dosage groups were below the limit of detection of the virus in their blood (less than 15 IU/mL) after 14 days.
In the early low-dose groups, after only three days of dosing, the mean reduction in viral load levels was 0.6 log(10) IU/mL greater with combination treatment (-2.9), compared to the performance of the individual compounds when administered as a single agent (-0.46 and -1.84 for R7128 and R7227, respectively). This suggests an additive effect for the combination.
No treatment-related serious adverse events (SAEs), no dose reductions and no discontinuations were reported in the study. Pharmacokinetic analysis confirmed that there were no drug-drug interactions between the compounds.
Next Steps in the Development Program
The companies are now exploring twice-daily dosing of R7227 and higher total daily doses (600 mg twice-daily and 900 mg twice-daily) than those explored in the first patient cohorts of INFORM-1. The companies also plan to explore the innovative DAA combination therapy in "treatment-experienced" patients with HCV, or those who did not achieve SVR with a previous interferon-based treatment.
Other Clinical Studies with R7227 and R7128
In addition to clinical studies of combination DAA regimens such as those studied in INFORM-1, R7227 and R7128 each are proceeding rapidly in development in combination with Roche's PEGASYS® (peginterferon alfa-2a) and COPEGUS® (ribavirin). A Phase IIb study with R7128 has now begun, while a Phase IIb study with R7227 is slated to begin in the summer.
The Foundation and Future of HCV Treatment
Combination therapy of pegylated interferon and ribavirin is the current standard of care for HCV. PEGASYS is the leading treatment for HCV, and also is the pegylated interferon therapy of choice for most HCV antiviral agents in development -- including those developed through collaborations with Roche, as well as those developed by other companies. The collaborations with InterMune and Pharmasset position Roche as a leader in developing innovative treatments for HCV.
Dial-In and Webcast Details
InterMune and Pharmasset will host a live webcast of a discussion of the INFORM-1 results from the EASL conference today, Saturday, April 25, 2009, at 7:00 p.m. CEST (1:00 p.m. EDT). Participating in the discussion will be Dr. Ed Gane, principal investigator in the INFORM-1 trial. Members of management from Roche, InterMune and Pharmasset will also be available to answer questions. A live webcast and slide presentation will be available through the Investor Relations pages of both InterMune and Pharmasset at www.intermune.com or www.pharmasset.com, respectively. Alternatively, interested parties may access the discussion and ask questions by dialing 888-799-0528 (U.S. and Canada) or 973-200-3372 (international), conference ID # 95452531. A webcast replay will be available approximately three hours after the call and will be archived at www.intermune.com and at http://www.pharmasset.com.
The teleconference replay will be available for 10 business days following the call and can be accessed by dialing 800-642-1687 (U.S. and Canada) or 706-645-9291 (international), and entering conference ID # 95452531.
The companies recommend logging on at least 15 minutes prior to the start of the webcast to ensure adequate time for any software downloads that may be required.
About R7227 (ITMN-191)
R7227 is a potent, macrocyclic inhibitor of HCV NS3/4A protease activity, and has produced multi-log(10) reductions in levels of HCV levels in chronic HCV patients, when administered for 14 days as monotherapy and when combined with PEGASYS and COPEGUS. R7227 was safe and well-tolerated in these studies.
About R7128
R7128, a cytidine nucleoside analog inhibitor of HCV RNA polymerase, is being developed for the treatment of chronic HCV infection. R7128 has shown potent in vivo activity against all of the most common HCV genotypes (1, 2 and 3). R7128 was safe and well-tolerated when given with PEGASYS and COPEGUS for up to 28 days.
About PEGASYS
PEGASYS, in combination with COPEGUS (ribavirin), is indicated for the treatment of adults with chronic HCV who have compensated liver disease and have not previously been treated with interferon alpha. Efficacy has been demonstrated in patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A) and patients with HIV disease that are clinically stable (e.g., antiretroviral therapy not required or receiving stable antiretroviral therapy). In addition, PEGASYS in combination with COPEGUS is the first and only FDA-approved regimen for the treatment of chronic HCV in patients coinfected with HCV and HIV. PEGASYS is the only pegylated interferon indicated for the treatment of adult patients with chronic hepatitis B (HBeAg positive and HBeAg negative chronic hepatitis B who have compensated liver disease and evidence of viral replication and liver inflammation).
PEGASYS is dosed at 180mcg as a subcutaneous injection taken once a week. COPEGUS is available as a 200mg tablet, and is administered orally two times a day as a split dose. Roche has backed PEGASYS with the most extensive clinical research program ever undertaken in HCV, with major studies initiated to advance treatment for HCV patients with unmet needs, including patients co-infected with HIV and HCV, African Americans, patients with cirrhosis, and patients who have failed to respond to previous therapy.
Important Safety Information About PEGASYS
PEGASYS, alone or in combination with COPEGUS, is indicated for the treatment of adults with chronic hepatitis C virus infection who have compensated liver disease and have not been previously treated with interferon alpha. Patients in whom efficacy was demonstrated included patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A).
Alpha interferons, including PEGASYS® (Peginterferon alfa-2a), may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping PEGASYS therapy (see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS in complete product information).
Use with Ribavirin. Ribavirin, including COPEGUS®, may cause birth defects and/or death of the fetus. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin causes hemolytic anemia. The anemia associated with ribavirin therapy may result in a worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen (see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS in complete product information).
PEGASYS is contraindicated in patients with hypersensitivity to PEGASYS or any of its components, autoimmune hepatitis, and hepatic decompensation (Child-Pugh score greater than 6; class B and C) in cirrhotic CHC monoinfected patients before or during treatment. PEGASYS is also contraindicated in hepatic decompensation with Child-Pugh score greater than or equal to 6 in cirrhotic CHC patients coinfected with HIV before or during treatment. PEGASYS is also contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurological and other complications in neonates and infants, which are sometimes fatal. PEGASYS and COPEGUS therapy is additionally contraindicated in patients with a hypersensitivity to COPEGUS or any of its components, in women who are pregnant, men whose female partners are pregnant, and patients with hemoglobinopathies (eg, thalassemia major, sickle-cell anemia).
COPEGUS THERAPY SHOULD NOT BE STARTED UNLESS A REPORT OF A NEGATIVE PREGNANCY TEST HAS BEEN OBTAINED IMMEDIATELY PRIOR TO INITIATION OF THERAPY. Women of childbearing potential and men must use two forms of effective contraception during treatment and during the 6 months after treatment has concluded. Routine monthly pregnancy tests must be performed during this time. If pregnancy should occur during treatment or during 6 months post-therapy, the patient must be advised of the significant teratogenic risk of COPEGUS therapy to the fetus. Healthcare providers and patients are strongly encouraged to immediately report any pregnancy in a patient or partner of a patient during treatment or during 6 months after treatment cessation to the Ribavirin Pregnancy Registry at 1-800-593-2214.
Chronic hepatitis C (CHC) patients with cirrhosis may be at risk of hepatic decompensation and death when treated with alpha interferons, including PEGASYS. During treatment, patients' clinical status and hepatic function should be closely monitored, and PEGASYS treatment should be immediately discontinued if decompensation (Child-Pugh score greater than or equal to 6) is observed. Ischemic and hemorrhagic cerebrovascular events have been observed in patients treated with interferon alfa-based therapies, including PEGASYS. Events occurred in patients with few or no reported risk factors for stroke, including patients less than 45 years of age. Because these are spontaneous reports, estimates of frequency cannot be made and causal relationship between interferon alfa-based therapies and these events is difficult to establish.
The most common adverse events reported for PEGASYS and COPEGUS combination therapy observed in clinical trials were fatigue/asthenia (65 percent), headache (43 percent), pyrexia (41 percent), myalgia (40 percent), irritability/anxiety/nervousness (33 percent), insomnia (30 percent), alopecia (28 percent), neutropenia (27 percent), nausea/vomiting (25 percent), rigors (25 percent), anorexia (24 percent), injection site reaction (23 percent), arthralgia (22 percent), depression (20 percent), pruritus (19 percent) and dermatitis (16 percent).
Serious adverse events in hepatitis C trials included neuropsychiatric disorders (homicidal ideation, suicidal ideation, suicide attempt, suicide, psychotic disorder and hallucinations), serious and severe bacterial infections (sepsis), bone marrow toxicity (cytopenia and rarely, aplastic anemia), cardiovascular disorders (hypertension, supraventricular arrhythmias and myocardial infarction), hypersensitivity (including anaphylaxis), endocrine disorders (including thyroid disorders and diabetes mellitus), autoimmune disorders (including idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, psoriasis, lupus, rheumatoid arthritis and interstitial nephritis), pulmonary disorders (dyspnea, pneumonia, bronchiolitis obliterans, interstitial pneumonitis and sarcoidosis), colitis (ulcerative and hemorrhagic/ischemic colitis), pancreatitis, and ophthalmologic disorders (decrease or loss of vision, retinopathy including macular edema and retinal thrombosis/hemorrhages, optic neuritis and papilledema).
Adverse reactions reported during post-approval use of PEGASYS therapy, with and without ribavirin, include hearing impairment, hearing loss, serious skin reactions, including erythema multiforme major, and infections (bacterial, viral and fungal).
About Roche
Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. pharmaceuticals headquarters of the Roche Group, one of the world's leading research-oriented healthcare groups with core businesses in pharmaceuticals and diagnostics. For more than 100 years in the U.S., Roche has been committed to developing innovative products and services that address prevention, diagnosis and treatment of diseases, thus enhancing people's health and quality of life. For additional information about the U.S. pharmaceuticals business, visit our website http://www.rocheusa.com. Product and treatment information for U.S. healthcare professionals is available at www.RocheExchange.com.
About InterMune
InterMune is a biotechnology company focused on the research, development and commercialization of innovative therapies in pulmonology and hepatology. InterMune has a pipeline portfolio addressing idiopathic pulmonary fibrosis (IPF) and hepatitis C virus (HCV) infections. The pulmonology portfolio includes the Phase III program, CAPACITY, which is evaluating pirfenidone as a possible therapeutic candidate for the treatment of patients with IPF and a research program focused on pirfenidone analog ITMN-520. The hepatology portfolio includes the HCV protease inhibitor compound R7227 (ITMN-191), a second-generation HCV protease inhibitor research program, and a research program evaluating a new target in hepatology. For additional information about InterMune and its R&D pipeline, please visit www.intermune.com.
About Pharmasset
Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is on the development of oral therapeutics for the treatment of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Pharmasset is currently developing three product candidates. R7128, an oral treatment for chronic HCV infection, has completed a 4-week clinical trial in combination with PEGASYS plus COPEGUS through a strategic collaboration with Roche, and is initiating a Phase IIb trial. Racivir, which is being developed for the treatment of HIV in combination with other approved HIV drugs, has completed a Phase II clinical trial. PSI-7851, an unpartnered second generation HCV nucleotide analogue recently entered Phase I studies. Additional information is available on the Internet at http://www.pharmasset.com
Forward-Looking Statements
This news release contains forward-looking statements within the meaning of section 21E of the Securities Exchange Act of 1934, as amended, that reflect the companies' judgments and involve risks and uncertainties as of the date of this release, including without limitation the statements related to anticipated product development timelines. All forward-looking statements and other information included in this press release are based on information available to the companies as of the date hereof, and the companies assume no obligation to update any such forward-looking statements or information. Actual results could differ materially from those described in the forward-looking statements.
Factors that could cause or contribute to such differences include, but are not limited to, those discussed in detail under the heading "Risk Factors" in the companies' most recent annual reports on Form 10-K filed with the SEC and in other periodic reports filed with the SEC. The risks and other factors discussed above should be considered only in connection with the fully discussed risks and other factors discussed in detail in the respective Forms 10-K and in the companies' other periodic reports filed with the SEC, all of which are available via their respective web sites at www.intermune.com and .
All trademarks used or mentioned in this release are protected by law.
- About INFORM-1: www.clinicaltrials.gov
(1) "First-In-Man Demonstration Of Potent Antiviral Activity with a Nucleoside Polymerase (R7128) and Protease (R7227/ITMN-191) Inhibitor Combination in HCV: Safety, Pharmacokinetics, and Virologic Results from INFORM-1," Abstract #1046: to be presented at 44th Annual Meeting of the European Association for the Study of the Liver (EASL) in Copenhagen, Denmark, April 22 - 26, 2009.
Contacts:
Linda Dyson
Roche
973-562-2231 (office)
973-986-5973 (mobile)
Linda.Dyson@roche.com
Jim Goff
Sr. Director, Corp. Comm. & IR
InterMune, Inc.
415-466-2228
jgoff@intermune.com
Richard E. T. Smith, Ph.D.
VP, Investor Relations and Corporate Communications
Pharmasset
609-613-4181
richard.smith@pharmasset.com
so the people most likely to get the flu are people that are also pigs
is that right
what if someone with swine flu,someone with bird flue and someone with human flu have a three way
well the best business proposition is to develop the first oral cocktail, supplant telaprevir, and maintain the pegasys franchise in HCV. if roche compares direct acting agents with and without soc follow on i think they are setting the all oral cocktail up for failure. lets see if they do the right thing and examine every permutation and combination individually - i.e. minus rib only, minus inf only, and minus both to see what can and can't be dropped from the regimen
You may not get as high a percentage of svr in the patients with the totally oral combo as soc but that wouldn't be a failure. The biggest problem in hep c is that patients don't feel sick until they take ifn. So if you take the oral combo and it works fine. If it fails you can still take standard of care so you lost nothing.
Roche and Pharmasset Initiate Phase IIb Clinical Trial of R7128, Most Advanced Nucleoside Polymerase Inhibitor in Development for Chronic Hepatitis C
On Friday April 24, 2009, 7:35 pm EDT
I Believe an error in the press release
In the harder to treat populations of genotype 2 or 3 patients who had not responded to previous therapy, results with R7127 s/b R7128 1500mg twice-daily in combination with the standard of care showed that 90 percent of patients achieved undetectable levels of HCV(<15 IU/ml) after 4 weeks, compared to 60 percent in the standard of care arm.
Start of trial triggers $10 million milestone payment to Pharmasset
PRINCETON, N.J., April 24 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS - News) and Roche (Roche SWX: RO, ROG; Pink Sheets: RHHBY) today announced that the first patient has been dosed in a Phase IIb study of R7128, the nucleoside polymerase inhibitor most advanced in development for the treatment of chronic hepatitis C (HCV). The trial will evaluate the dose and duration of treatment of R7128 in combination with Roche's PEGASYS® (peginterferon alfa-2a) and COPEGUS® (ribavirin) - in HCV patients who have not been treated previously. The goal of adding R7128 to the existing standard therapy is to improve rates of sustained virological response (SVR) and to shorten the length of treatment for patients.
R7128 is being developed by Roche and Pharmasset under a partnership agreement entered into in 2004. The first patient dosed in this study triggered a $10 million payment to Pharmasset from Roche.
A Phase I/IIa trial demonstrated the ability of R7128 to generate high rapid virologic response rates (RVR) in combination with PEGASYS and COPEGUS. Unlike protease inhibitors in development, R7128 is active against multiple HCV genotypes and presents a high barrier to the development of resistance.
"We look for the Phase IIb study to further support the efficacy and safety of R7128, and nucleoside polymerase inhibitors as a class," said Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "We believe nucleoside inhibitors have a number of advantages over other classes of HCV drugs, including a higher barrier to resistance and activity across multiple genotypes, as well as a high level of potency."
"The collaboration with Pharmasset underscores Roche's commitment to develop new therapies that will meet the needs of a growing population of patients with hepatitis C," said Rob Mitchell, Global Head of Roche's Virology business. "We are hopeful that a combination of R7128 and the current gold standard of PEGASYS and COPEGUS can provide a more potent - and potentially shorter - treatment regimen."
These collaborations position Roche as a leader, and they underscore Roche's role as a pioneer, in the next evolution of hepatology treatments.
About the Phase IIb Trial
The Phase IIb trial is anticipated to enroll about 400 HCV-infected patients with genotypes 1 or 4 who have not been treated previously. The primary efficacy endpoint of the trial will be the proportion of patients who achieve an SVR, defined as undetectable levels of HCV (measured by Roche TaqMan assay) 24 weeks after completion of treatment. The trial will be conducted in North America, Europe and Australia. Patients will be enrolled into one of 5 arms:
24 weeks of total treatment, with R7128 500mg bid in combination with PEGASYS and COPEGUS for 12 weeks, followed by 12 weeks of PEGASYS and COPEGUS ("12+12")
24 weeks of total treatment, with R7128 1000mg bid in combination with PEGASYS and COPEGUS for 12 weeks, followed by 12 weeks of PEGASYS and COPEGUS ("12+12")
24 weeks of total treatment, with R7128 1000mg bid in combination with PEGASYS and COPEGUS for 8 weeks, followed by a further 16 weeks of PEGASYS and COPEGUS ("8+16")
48 weeks of total treatment, with R7128 1000mg bid in combination with PEGASYS and COPEGUS for 12 weeks, followed by a further 36 weeks of PEGASYS and COPEGUS ("12+36")
A control arm with PEGASYS and COPEGUS for 48 weeks.
Patients in the 24-week arms will discontinue all treatment at week 24 if they have achieved RVR, defined as undetectable levels of HCV at week 4 (a strategy known as "RVR-guided" treatment), and maintain undetectable levels of HCV until week 22. Patients who do not achieve an RVR at week 4 will continue on the standard of care until week 48.
According to the study design, 100 patients will be initially enrolled, equally across all five arms. The remaining 300 will be enrolled following a review of the 12-week data by the data safety monitoring board.
More About R7128
R7128, a cytidine nucleoside analog inhibitor, is being developed for the treatment of chronic HCV infection. R7128 has shown in vitro activity against all of the most common HCV genotypes.
In a 4-week Phase I combination study conducted in 81 treatment-naive patients with chronic HCV, R7128 demonstrated significant short-term antiviral activity with safety and tolerability comparable to placebo with standard of care. Up to 88 percent of patients achieved undetectable levels of HCV (<15 IU/ml) after only 4 weeks of treatment with R7128 1000mg bid and the standard of care, compared to 18.75 percent treated with the standard of care alone.
In the harder to treat populations of genotype 2 or 3 patients who had not responded to previous therapy, results with R7127 1500mg twice-daily in combination with the standard of care showed that 90 percent of patients achieved undetectable levels of HCV(<15 IU/ml) after 4 weeks, compared to 60 percent in the standard of care arm.
In November 2008, Roche, Pharmasset and InterMune initiated the INFORM-1 trial to investigate the combination of R7128 with InterMune's R7227, a protease inhibitor, in HCV patients. This is the first-ever clinical study to investigate the combination of two oral antiviral medicines in the absence of weekly injections of interferon, or ribavirin. Interim results of this trial will be presented this weekend at the European Association of Liver Disease (EASL) meeting being held in Copenhagen, Denmark.
About Hepatitis C
The hepatitis C virus (HCV) is transmitted primarily through blood or blood products. HCV chronically affects 180 million people worldwide, which makes it over four times more prevalent than HIV.(i,ii) It is a leading cause of cirrhosis, liver cancer and liver failure.
About Pharmasset
Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is on the development of oral therapeutics for the treatment of hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Pharmasset is currently developing three product candidates. R7128, an oral treatment for chronic HCV infection, has completed a 4-week clinical trial in combination with PEGASYS plus COPEGUS through a strategic collaboration with Roche, and is initiating a Phase IIb trial. Racivir, which is being developed for the treatment of HIV in combination with other approved HIV drugs, has completed a Phase II clinical trial. PSI-7851, an unpartnered second generation HCV nucleotide analogue recently entered Phase I studies.
Pharmasset Forward-Looking Statements
Pharmasset "Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release regarding our business that are not historical facts are "forward-looking statements" that involve risks and uncertainties, including without limitation, the risk that adverse events could cause the cessation or delay of any of the ongoing or planned clinical trials and/or our development of our product candidates, the risk that the results of previously conducted studies involving our product candidates will not be repeated or observed in ongoing or future studies involving our product candidates, the risk that our collaboration with Roche will not continue or will not be successful and the risk that any one or more of our product candidates will not be successfully developed and commercialized. For a discussion of these risks and uncertainties, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section of our Annual Report on Form 10-K for the fiscal year ended September 30, 2008 and our Quarterly Report on Form 10-Q for the period ended December 31, 2008 filed with the Securities and Exchange Commission entitled "Risk Factors" and discussions of potential risks and uncertainties in our subsequent filings with the Securities and Exchange Commission.
About PEGASYS
Combination therapy of pegylated interferon and ribavirin is the current standard of care for the hepatitis C virus (HCV), and PEGASYS is the U.S. and global market-leading treatment for this disease. PEGASYS is also the pegylated interferon therapy of choice for most HCV antiviral agents in development.
PEGASYS, in combination with COPEGUS (ribavirin), is indicated for the treatment of adults with chronic HCV who have compensated liver disease and have not previously been treated with interferon alpha. Efficacy has been demonstrated in patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A) and patients with HIV disease that are clinically stable (e.g., antiretroviral therapy not required or receiving stable antiretroviral therapy). In addition, PEGASYS in combination with COPEGUS is the first and only FDA-approved regimen for the treatment of chronic HCV in patients coinfected with HCV and HIV. PEGASYS is the only pegylated interferon indicated for the treatment of adult patients with chronic hepatitis B (HBeAg positive and HBeAg negative chronic hepatitis B who have compensated liver disease and evidence of viral replication and liver inflammation).
PEGASYS is dosed at 180mcg as a subcutaneous injection taken once a week. COPEGUS is available as a 200mg tablet, and is administered orally two times a day as a split dose. Roche has backed PEGASYS with the most extensive clinical research program ever undertaken in HCV, with major studies initiated to advance treatment for HCV patients with unmet needs, including patients co-infected with HIV and HCV, African Americans, patients with cirrhosis, and patients who have failed to respond to previous therapy.
IMPORTANT SAFETY INFORMATION
PEGASYS, alone or in combination with COPEGUS, is indicated for the treatment of adults with chronic hepatitis C virus infection who have compensated liver disease and have not been previously treated with interferon alpha. Patients in whom efficacy was demonstrated included patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A).
Alpha interferons, including PEGASYS® (Peginterferon alfa-2a), may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping PEGASYS therapy (see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS in complete product information).
Use with Ribavirin. Ribavirin, including COPEGUS®, may cause birth defects and/or death of the fetus. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin causes hemolytic anemia. The anemia associated with ribavirin therapy may result in a worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen (see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS in complete product information).
PEGASYS is contraindicated in patients with hypersensitivity to PEGASYS or any of its components, autoimmune hepatitis, and hepatic decompensation (Child-Pugh score greater than 6; class B and C) in cirrhotic CHC monoinfected patients before or during treatment. PEGASYS is also contraindicated in hepatic decompensation with Child-Pugh score greater than or equal to 6 in cirrhotic CHC patients coinfected with HIV before or during treatment. PEGASYS is also contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurological and other complications in neonates and infants, which are sometimes fatal. PEGASYS and COPEGUS therapy is additionally contraindicated in patients with a hypersensitivity to COPEGUS or any of its components, in women who are pregnant, men whose female partners are pregnant, and patients with hemoglobinopathies (eg, thalassemia major, sickle-cell anemia).
COPEGUS THERAPY SHOULD NOT BE STARTED UNLESS A REPORT OF A NEGATIVE PREGNANCY TEST HAS BEEN OBTAINED IMMEDIATELY PRIOR TO INITIATION OF THERAPY. Women of childbearing potential and men must use two forms of effective contraception during treatment and during the 6 months after treatment has concluded. Routine monthly pregnancy tests must be performed during this time. If pregnancy should occur during treatment or during 6 months post-therapy, the patient must be advised of the significant teratogenic risk of COPEGUS therapy to the fetus. Healthcare providers and patients are strongly encouraged to immediately report any pregnancy in a patient or partner of a patient during treatment or during 6 months after treatment cessation to the Ribavirin Pregnancy Registry at 1-800-593-2214.
Chronic hepatitis C (CHC) patients with cirrhosis may be at risk of hepatic decompensation and death when treated with alpha interferons, including PEGASYS. During treatment, patients' clinical status and hepatic function should be closely monitored, and PEGASYS treatment should be immediately discontinued if decompensation (Child-Pugh score >=6) is observed. Ischemic and hemorrhagic cerebrovascular events have been observed in patients treated with interferon alfa-based therapies, including PEGASYS. Events occurred in patients with few or no reported risk factors for stroke, including patients less than 45 years of age. Because these are spontaneous reports, estimates of frequency cannot be made and causal relationship between interferon alfa-based therapies and these events is difficult to establish.
The most common adverse events reported for PEGASYS and COPEGUS combination therapy observed in clinical trials were fatigue/asthenia (65 percent), headache (43 percent), pyrexia (41 percent), myalgia (40 percent), irritability/anxiety/nervousness (33 percent), insomnia (30 percent), alopecia (28 percent), neutropenia (27 percent), nausea/vomiting (25 percent), rigors (25 percent), anorexia (24 percent), injection site reaction (23 percent), arthralgia (22 percent), depression (20 percent), pruritus (19 percent) and dermatitis (16 percent).
Serious adverse events in hepatitis C trials included neuropsychiatric disorders (homicidal ideation, suicidal ideation, suicide attempt, suicide, psychotic disorder and hallucinations), serious and severe bacterial infections (sepsis), bone marrow toxicity (cytopenia and rarely, aplastic anemia), cardiovascular disorders (hypertension, supraventricular arrhythmias and myocardial infarction), hypersensitivity (including anaphylaxis), endocrine disorders (including thyroid disorders and diabetes mellitus), autoimmune disorders (including idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, psoriasis, lupus, rheumatoid arthritis and interstitial nephritis), pulmonary disorders (dyspnea, pneumonia, bronchiolitis obliterans, interstitial pneumonitis and sarcoidosis), colitis (ulcerative and hemorrhagic/ischemic colitis), pancreatitis, and ophthalmologic disorders (decrease or loss of vision, retinopathy including macular edema and retinal thrombosis/hemorrhages, optic neuritis and papilledema). Adverse reactions reported during post-approval use of PEGASYS therapy, with and without ribavirin, include hearing impairment, hearing loss, serious skin reactions, including erythema multiforme major, and infections (bacterial, viral and fungal).
your wife?
We allow, as a matter of public policy, businesses to be owned and operated as corporations, limited partnerships and limited liability companies and confer on the owners the right to avoid liability of the obligations of the entities.
That is good policy, IMO. It has allowed the creation of great wealth.
It is good policy, the problem here is that Citadel and Mercedes underfunded the pension, that is why it is in the shithole. So they should not be forgiven the pension underfunding, the other debts can be part of the bankrupcy
believe they just surrendered their equity. Didn't mercedes still have a piece?
Citadel and Mercedes underfunded the pension so they should make it whole.
but why is Citadel off the hook?
why shouldn't Citadel have to be responsible for the pensions
they knew the risk when they bought the company.
so we are not only bailing out the pension, we are bailing out Citadel
now they can buy some cheap toxic assets and be levered up by the treasury on that purchase.
It is a great country this america if you run a multibillion dollar Venture capital fund.
As we have maintained in the last year and half that it will be the case, Avastin
colorectal adjuvant trial failed to meet its primary end point. So, the Academy Award
goes to...... Sue Helmann and the rest of former Genentech management team. In their
final commanding performance, through their optimism on the trial they were able to
extract $6 more from Roche. Former Genentech shareholders should be very happy that they
did so.
Alex To isn't posting this to this board. I received this email
Alex To, MD
Managing Member
Cross Current Research LLC
2 Research Way, 2nd Fl
Princeton, NJ 08540
609-243-0082
917-584-6903 (cell)
I can't understand how they wouldn't see the increase in liver enzymes way before phase 3 was done or almost done.
with all the sophisticated computer models companies have access to there has to be a way to predict these effects on the liver in an earlier stage of testing.
vrus is the pure play hep c play
intermune could get some kind of negative news on the ipf product.
you got a bug up your butt?
the only recently got the data on their drugs. if they would have partnered before the data they couldn't get as much.
I tried to call you but your number is changed
Propulsid (licensed to jnj the more toxic isomer it turned out).....
ARYX makes proven therapies safer
http://www.aryx.com/swf/ARYX_MOA.html
fact sheets
http://www.aryx.com/pdf/aryx_ati-7505.pdf
http://www.aryx.com/pdf/aryx_ati-2042.pdf
http://www.aryx.com/pdf/aryx_ati-5923.pdf
http://www.aryx.com/pdf/aryx_ati-9242.pdf
Protellos five year data
The Strength Of Strontium Ranelate - Protects Bones For At Least Five Years, Remodels Bone Architecture
05 Jun 2006
In previous clinical trials strontium ranelate has proven effective in preventing fractures for up to three years. But according to new data presented today at the IOF World Congress on Osteoporosis in Toronto, Canada that window of opportunity can now be extended to at least five years.
Jean-Yves Reginster, Professor of Epidemiology, Public Health and Health Economics at the University of Liege, Belgium, reported (see conference Abstract No. OC24) that in the phase III Spinal Osteoporosis Therapeutic Intervention (SOTI) trial, strontium ranelate reduced the risk of new vertebral fractures by about 30 percent over four years. In the Treatment Of Peripheral Osteoporosis (TROPOS) trial, which has been running a little longer, those taking the drug for five years had about a 25 percent reduction in vertebral fractures and a 15 percent reduction in non-vertebral fractures, such as those of the thigh. �These results demonstrate, uniquely for anti-osteoporotic treatments, that strontium ranelate provides sustained efficacy over five years against both vertebral and non-vertebral fractures,� said Reginster.
Because other existing treatments have not demonstrated such robust effects in prospective, pre-planned, double-blind, placebo-controlled studies, postmenopausal osteoporotic women stand to benefit from the proven efficacy and tolerability of strontium treatment, according to Reginster.
In two other studies presented at the IOF WCO this week, Georges Boivin and colleagues at the INSERM, Universite Claude Bernard, Lyon, France and J. Yebin Jiang and colleagues at the University of California and the University of Michigan Osteoporosis and Arthritis Lab report on just how strontium ranelate contributes to bone strength.
Boivin (see conference Abstract No. P310) reported that strontium is incorporated into new bone but does not make its way into older bone, which remains virtually free of strontium even after three years of treatment. His findings, based on high resolution X-ray microanalysis, also suggests that strontium does not affect the quality of the bone mineral, but it does affect the quantity. �We believe that the microarchitecture of bone is improved in those taking strontium ranelate. It appears that the bone mass is increased with a normal degree of mineralization,� said Boivin. The best way to think of this is to imagine bone as a tube filled with styrofoam packing. On strontium ranelate, the nature of the packing does not change, but the amount of packing and how it fits together does.
That theory is supported by the findings of Jiang and colleagues, who reported (see conference Abstract No. OC40) that strontium does, in fact, rearrange bone architecture. Bone is made up of two different types of structure, a spongier honeycomb core and a harder outside layer called cortical bone. Jiang reported that the bone making up the honeycomb appears as flatter, plate-like mineral in samples taken from patients treated with strontium ranelate, whereas in control samples the bone appears as rod-like structures. He also reported that the outer cortical bone becomes thicker. �The three-dimensional changes in trabecular and cortical bone may improve bone mechanical strength, explaining the decreased risk for fracture in those on strontium ranelate treatment,� said Jiang.
Both groups obtained their data by analyzing biopsies taken from those enrolled in the TROPOS, SOTI and also the STRATOS phase II clinical trials for strontium ranelate. Boivin and colleagues used high resolution X-ray microradiography to determine the degree of mineralization of pelvic bone samples. Jiang and colleagues used a sophisticated micro computerized tomography scanner, better known as a micro CAT scanner, to measure the three-dimensional structure of the bone, also taken from the pelvis. Boivin compared 35 samples taken from patients treated with various doses of strontium ranelate, with 22 samples taken from those given placebo. Jiang and colleagues measured similar numbers of samples, 20 from the treatment group and 21 controls.
Bisphophonates - Medicine that Keeps on Giving
Boivin's findings also suggest that because strontium is laid down at the surface of newly formed bone mineral, it may be rapidly cleared from the bone once treatment is stopped. Bisphosphonates, on the other hand, are released only very slowly from bone and continue to appear in the urine for years after treatment is stopped according to researchers from the Netherlands (see conference Abstract No. OC25). The finding should caution against prescribing the drugs for young girls who suffer from osteoporosis or brittle bone disorders such as osteogenesis imperfecta.
Bisphosphonates are the most widely prescribed treatment for those with, or at risk for, osteoporosis. Like strontium, bisphosphonates are incorporated into bone where they stop the bone mineral from being dissolved away. They are known to be slowly released from bone but just how long they remain imbedded in the mineral is uncertain. However, at the IOF WCO, Socrates Papapoulos and colleagues at Leiden University, report that the bisphosphonate pamidronate can still be detected in urine eight years after treatment has stopped.
�Up to now it has been hypothesized in the literature that bisphosphonates trapped in the bone are slowly released once therapy is stopped, but now we show for the first time that that phenomenon is real,� said Papapoulous.
The researchers tested urine samples from 6 children who had been given pamidronate for 4-10 years. Urinary measurements were taken up to 13 years after treatment was suspended. Pamidronate was measurable in urine of all patients except one, who had received treatment for 6 years, and drug was measured 13 years after stopping treatment.
The long half-life of bone bisphosphonates probably explains why osteoporotic women who have taken bisphosphonates for a long time have reduced bone mineral loss after stopping treatment. But there is a small cloud to this silver lining-�we need to be cautious about administering bisphosphonates to young girls because there is very little data on the effects of these drugs on embryonic development,� said Papapoulous.
Combination Therapy Packs One-Two Punch
Silvano Adami, University of Verona, Italy, and colleagues reported that women who have completed a course of another hormone therapy, parathyroid hormone, maintain better bone strength if they begin taking the Selective Estrogen Receptor Modulator (SERM) raloxifene once the parathyroid treatment has ended (see conference Abstract No. OC22).
�The results tell us that after a course of parathyroid treatment it is important to begin taking an anti-resorber, such as raloxifene, as soon as possible,� said Adami.
Parathyroid hormone is one of very few therapies that actually stimulates bone formation but the treatment is limited to two years or less in most countries. This has left doctors and patients wondering what the best course of action is once the hormone therapy has ended. SERMs are compounds that mimic only some of the action of estrogen. As such, they have different efficacies and side effects to hormone replacement therapy.
Adami and colleagues measured bone mineral density in 329 women who had been on parathyroid for one year then switched to either raloxifene or a placebo for a subsequent year. The researchers found that at the end of the second year, women who followed the parathyroid therapy with the estrogen mimic had a 2.3% higher bone density at the hip than those who had taken a placebo after the hormone treatment.
The researchers are planning to continue this study to see how long the benefit of the sequential parathyroid/raloxifene therapy persists.
Problems with New Hormone Replacement Therapy
In the recent LIFT trial to measure the efficacy of the estrogen hormone replacement therapy tibolone. Steve Cummings, Director of the San Francisco Coordinating Center, University of California, San Francisco and lead investigator, reported that follow up analysis showed that women who had taken the drug had about half as many vertebral fractures as those who had taken placebo (see conference Abstract No.OC38).
However, this trial was halted due to increased incidence of stroke. �The increased risk of stroke was unexpected and will limit the use of tibolone for prevention of osteoporosis and fracture,� said Cummings. He also suggested that women and physicians should weigh the benefits and risks and consider alternatives before prescribing tibolone for any indication.
Osteoporosis, in which the bones become porous and break easily, is one of the world's most common and debilitating diseases. The result: pain, loss of movement, inability to perform daily chores, and in many cases, death. One out of three women over 50 will experience osteoporotic fractures, as will one out of five men 1, 2, 3. Unfortunately, screening for people at risk is far from being a standard practice. Osteoporosis can, to a certain extent, be prevented, it can be easily diagnosed and effective treatments are available.
The International Osteoporosis Foundation (IOF) is the only worldwide organization dedicated to the fight against osteoporosis. It brings together scientists, physicians, patient societies and corporate partners. Working with its 170 member societies in 84 locations, and other healthcare-related organizations around the world, IOF encourages awareness and prevention, early detection and improved treatment of osteoporosis.
1 Melton U, Chrischilles EA, Cooper C et al. How many women have osteoporosis? Journal of Bone Mineral Research, 1992; 7:1005-10
2 Kanis JA et al. Long-term risk of osteoporotic fracture in Malmo. Osteoporosis International, 2000; 11:669-674
3 Melton LJ, et al. Bone density and fracture risk in men. JBMR. 1998; 13:No 12:1915
IOF World Congress on Osteoporosis, held every two years, is the only global congress dedicated specifically to all aspects of osteoporosis. Besides the opportunity to learn about the latest science and developments in diagnosis, treatment and the most recent socio-economic studies, participants have the chance to meet and exchange ideas with other physicians from around the world. All aspects of osteoporosis will be covered during the Congress which will comprise lectures by invited speakers presenting cutting edge research in the field, and 35 oral presentations and more than 680 poster presentations selected from 720 submitted abstracts. More than 70 Meet the Expert Sessions covering many practical aspects of diagnosis and management of osteoporosis are also on the program.
For more information on osteoporosis and IOF please visit:
http://www.osteofound.org
Osteologix OLGX important info about phase 3
one phase 3 trial makes this easier to partner
We are designing our development plan for NB S101 for osteoporosis to comply with both U.S. and European guidelines. On February 17, 2009, we held a meeting with the FDA regarding the proposed development of NB S101. Based on feedback from the FDA meeting, we believe that the continued development of NB S101 will require an additional phase II trial and only one large, well-controlled phase III trial.
The FDA and EMEA require positive results from phase III studies before they will approve an NDA. In order to obtain approval for a new drug for the treatment of osteoporosis, current regulatory guidelines require placebo-controlled double-blind studies with fracture reduction as the primary endpoint. An adequate fracture-prevention trial represents a significant time and resource investment, as the treatment duration in the required clinical studies can be up to three years, although recent trials have been conducted with a two-year treatment duration and more recently an advisory group has recommended that these trials be reduced to 18 to 24 months in duration. These trials raise ethical questions concerning the use of placebo groups when approved drugs are available to treat osteoporosis, and both European and U.S. regulatory authorities are currently debating whether continued use of such trials can be recommended. If future guidelines prevent or limit the use of placebo control in such studies, we may plan to alternatively conduct a non-inferiority study against an established osteoporosis treatment or otherwise modify our plans based on any new guidelines established for approval of drugs to treat or prevent osteoporosis.
Based on the current FDA and EMEA guidelines and anticipated changes, we anticipate the primary objective of a phase III study will be to evaluate the ability of NB S101 to prevent incident vertebral fracture. We also anticipate that we would collect data on non-vertebral fractures, spine, hip and forearm BMD, and biochemical markers of bone and cartilage turnover. We estimate that the phase III study may enroll up to 3,000 osteoporotic women, comparing one dose of NB S101 to placebo over a two- to three-year treatment period, with a possible two-year extension. Based on continuing analysis of the phase II data and discussions with regulatory agencies, we are continuing statistical assessments before we finalize any phase III clinical trial design and determine the specific number of patients needed.
http://www.sec.gov/Archives/edgar/data/1...
page 9
OSTEOLOGIX (OLGX) this company has what appears to be a better drug than Protelos which is selling at a run rate of 300 million a year in Europe. It is over 60 percent owned by Nordic Biosciences, which is why the stock is so thinly traded. If you can build a position I believe there is huge upside.
Osteologix Announces Win Versus Opposition for its European Patent
Covering NBS-101 for Osteoporosis – Reiterating Buy on OLGX.
Highlights
• Osteologix wins in patent dispute in Europe as its NBS-101 patent is upheld by
the European Patent Office (EPO). We believe the upholding of the patent by the
EPO represents an important victory for Osteologix for a number of reasons
including: First, it validates the potential value of the product for a partnership in
Europe. Second, it validates the findings of enhanced bioavailability (BA) with the
malonate salt were not “obvious”. In other words, the EPO found, since the
malonate salt is not widely used or a well know salt in drug formulation and it has not
already been shown to demonstrate an increase in BA for a wide range of
compounds, it was not “obvious” malonate would increase BA. Third, the EPO
agreed malonate salt definitely increased BA. Fourth, it increases our confidence for
the issuance of the patent in the US by the USPTO. We expect the USPTO could
complete its review of the patent by 2Q 2009 and the issuance of the patent in the
U.S. would represent an important catalyst for the Company and its partnership
prospects for the product. For background on this patent: In May of 2003
(International filing date May 2004), Osteologix filed in the EU a patent entitled
“Water-soluble strontium salts for use in treatment of cartilage and/or bone
conditions” which protects strontium salts with specific water solubility profiles,
excluding strontium ranelate. The EPO issued this patent, European Patent # EP-
1,534,305B9, in October 2006, with an expiration date in May 2024. However, in
July 2007, Intellectual Property Services of Paris, France filed a Notice of Opposition
against Osteologix’s European Patent requesting the EPO revoke the entire patent.
Importantly, Osteologix conducted a wide series of chemical modeling and animal
tests to fully define the ideal solubility profile and to optimize the BA of strontium
using a wide variety of organic and inorganic salts. From this testing they identified
strontium malonate as the most ideal salt for development as an oral drug. They
also conducted a number of human clinical trials including Phase I PK/PD studies
and a Phase II trial demonstrating efficacy. Importantly, OLGX also filed IP
surrounding combination use of strontium with other therapies, and have
applications related to manufacturing, osteonecrosis, and arthritis.
As of September 30, 2008 Osteologix had $5.3 million in cash. We believe
Osteologix $5.3 million in cash as of September 30, 2008 represents sufficient cash
to design a Phase III program, continue work on the IP issuance and continue
negotiating with potential partners. We believe Osteologix could need to raise
additional capital to show strength to potential partners in order to maximize the
value of their asset.
• We reiterate our BUY rating. We continue to believe Osteologix represents a
unique opportunity to invest in a late-stage compound which addresses a large
indication at a very attractive valuation. Additionally, we believe USPTO action on a
key patent for the company expected during 2Q 2009 and confirmation of the
regulatory pathway from FDA expected later this year could serve as important
catalysts for OLGX.
Long-term (8 year) data for strontium ranelate (Protelos) detail the positive efficacy data for 893 patients.
Patients from two double-blind, placebo-controlled, five-year Phase III trials (SOTI Study and the TROPOS Study),
which included a total of 6740 postmenopausal women with osteoporosis, were enrolled into a three-year openlabel
extension study. All Protelos treated patients received 2g per day. The efficacy data clearly indicate bone
mineral density (lumbar >25% increase and femoral neck >10% increase) increased continuously during the study
in Protelos treated patients. Additionally, the cumulative incidence of vertebral (14.9% yrs 1-3 vs 13.7% yrs 5-8)
and non-vertebral (11.2% yrs 1-3 vs 12% yrs 5-8) fractures remained unchanged during the three year extension
study from the first three years of the controlled trials. We are impressed with BMD and fracture incidence results
as they verify the durability of Protelos’ efficacy and because they occurred despite an increased risk associated
with aging Protelos treatment
during the 3 year open label extension study mitigates an increase in vertebral or non-vertebral fracture rates as
the cumulative fracture incidence remained stable/unchanged during the three year extension study when
compared to the incidence observed during the first three years of the placebo-controlled phase in the SOTI and
TROPOS trials. We are impressed with BMD and fracture incidence results as they verify the durability of Protelos’
efficacy and they occurred despite an increased risk associated with aging.
Protelos sales have rebounded and continue to grow following reports of anaphylactic reactions during 4Q
2007. Strontium ranelate continues to show sales growth in Europe (we believe revenues are at >$300 million
annual run rate), being very strong in new markets, with moderated growth in certain countries. The rebound in the
revenue ramp during 2Q 2008, supports our belief that physicians will view the potential for anaphylactic reactions
essentially as a non-issue which must be monitored for and is addressable by discontinuation of therapy. The rate
of observed anaphylactic reactions is lower than that seen with several other approved drugs. We continue to
believe the occurrence of DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) associated with
strontium ranelate may be associated with the synthetic ranelate salt which is not used in any other therapeutic
agent. Investors should remember that NBS-101 is strontium malonate which is a naturally occurring salt used in a
couple other approved drugs.
Upcoming Milestones Product Event Timing
NBS-101 FDA regulatory meeting, Pre-Phase III 1Q 2009
NBS-101 Initiate Phase III program 2009
NBS-101 Partnership 2009
NBS-101 Action on Key IP by USPTO 2Q 2009
Osteologix reported 4Q 2008 results with a lower burn than expected. The
Company reported a net loss of $1.1 million, or ($0.04) per share versus our estimate of
a net loss of $1.8 million, or ($0.06) per share. Overall, the Company has a burn rate of
approximately $350,000 per month resulting in expenses which were $0.7 million lower
than our estimate. The lower expenses are largely due to a lower than estimated R&D
and SG&A expenses. We project 2009 operating expenses to be lower than 2008 with
R&D expenses of $1.65 million and SG&A expenses of $2.6 million. Additionally, based
on the status of the IP in the US and Europe combined with the Company’s ongoing
interaction with the FDA, we project OLGX could sign a partnership for NBS-101 by late
2009/early 2010. Further, we believe a number of catalysts expected during the next
three quarters including: of patent issuance by the USPTO for NBS-101; conclusion of
discussions with the FDA regarding the appropriate design of Phase III trials; and a
potential corporate partnership for NBS-101, could serve as important drivers for the
stock.
As of December 31, 2008 Osteologix had $4.4 million in cash. We believe
Osteologix $4.4 million in cash as of YE 2008 represents sufficient cash to design a
Phase III program, continue work on the IP issuance and continue negotiating with
potential partners. We believe Osteologix could need to raise additional capital to show
strength to potential partners in order to maximize the value of their asset.
• We reiterate our BUY rating. We continue to believe Osteologix represents a unique
opportunity to invest in a late-stage/Phase III-ready compound which addresses a large
indication at a very attractive valuation. Additionally, we believe USPTO action on a key
patent for the company expected during 2Q 2009 and confirmation of the regulatory
pathway from FDA expected later this year could serve as important catalysts for
OLGX.
there have been cases of Stevens-Johnson reported in europe. I doubt it will ever be approved here.
the biophosphonates have some severe side effects also, and the thought is that this sydrome is probably more due to the ranelate than the strontium. Another factor is that since the biovalabiltiy of the product Osteologix is better they would use less drug for the same efficacy, so the chance of side effects would be reduced.
The bigger reason to doubt approval is the fact that they need to find a partner to fund the expensive phase 3, than because of the that side effect. Then again, if approved it is a blockbuster so how could a big pharma not be willing to shell out about 80-100 million for a chance to get a blockbuster with such a great model,(the strontium ranelate sales).
Risk of severe hypersensitivity reactions from strontium ranelate-containing medicine
The European Medicines Agency (EMEA) has recommended immediate inclusion of strong warnings concerning the risk of severe hypersensitivity reactions in the summery of product characteristics and patient information leaflet patient for Protelos® and Osseor®, which contain strontium ranelate. The products were approved in the EU in September 2004 for the treatment of postmenopausal osteoporosis.
Up to now, there have been 16 cases of the so-called DRESS syndrome (Drug Rash with Eosinophilia Systemic Symptoms), which is a severe allergic reaction with rashes, fever and symptoms from internal organs, among patients treated with Protelos®/Osseor®. Hereof, two deaths have been reported to the EMEA following a total of 570,000 patient years of exposure. DRESS is a rare but serious condition, which has been described with some other drugs such as anticonvulsants, allopurinol, minocycline, abacavir and sulfasalazine. The reported serious reactions started between 3 and 6 weeks of the initiation of the treatment, with rash accompanied by fever, swollen glands and damage to liver and kidney.
Having assessed the available data, the EMEA's Committee for Medicinal Products for Human Use (CHMP) recommended that the product information be updated in a rapid procedure to include warnings on severe hypersensitivity syndromes, including DRESS, Stevens Johnson-Syndrome and musculoskeletal pain.
Patients are advised to stop treatment with Protelos® or Osseor® when a rash occurs and to seek medical advice.
For further information, please contact Chief Medical Officer Doris Stenver, Consumer Safety Division, tel. +45 4488 9247
If the intent is to deceive and given that the facts will be disclosed on April 28 where is the benefit?
not only could the company do a raise, but Mitchell Gold could actually sell personal stock. His press release that he met the primary endpoint probably opens up the window.
Leerink report on high cost of cancer drugs during recession
April 15, 2009
Reason for report:
MEDACORP - SURVEY
Howard Liang, Ph.D.
(617) 918-4857
Howard.Liang@leerink.com
Jonathan Eckard, Ph.D.
(617) 918-4844
Jonathan.Eckard@leerink.com
BIOTECHNOLOGY
Survey Finds a Negative Impact of the Recession on High-Cost
Cancer Drugs
• Bottom Line: Economic cycles are not known to affect drugs for serious
diseases. However, a MEDACorp survey of 79 US oncologists and
hematologists suggests that the use of high-cost cancer drugs may be
negatively impacted by the current recession. We believe this may
represent a challenging environment for CELG, OSIP and ONXX within
our coverage; however, we believe impact on ALXN may be more modest.
• MEDACorp survey suggests a noticeable decline in high-cost
cancer drug use due to the recession. 56% of the 79 surveyed US
oncologists and hematologists indicated that their use of high-cost oral
cancer drugs has been negatively affected by the current recession and
the magnitude of this reduction averaged 10.1% for the entire surveyed
sample. Similarly, 52% of the respondents indicated that their use of
high-cost IV cancer drugs was reduced and by an average of 8.7%. Of 15
respondents who have experience with ALXN's Soliris, 10 indicated no
impact, 5 indicated reduction in use, and the average decline due to
recession was estimated to be 5.5%.
• Inability of patients to afford the copay appears to be the primary
reason for reduction of cancer drug use due to recession, cited by
64% of the 39 respondents who provided an explanation.
• Globally the impact may be different in each country. As the key
reason for reduction of use is patient out-of-pocket cost, we expect the
global impact to vary depending on the reimbursement system. On the
basis of feedback from a European MEDACorp consultant ("consultant"),
we believe that the economic impact in major markets in continental
Europe may be more limited as there is no patient copay. Conversely, in
emerging markets such as China where the drugs are paid almost entirely
by patients out of pocket, we expect a bigger impact from the economy.
• Are there winners and losers? Physician comments indicate that
expensive oral cancer agents, such as CELG's Revlimid, OSIP's Tarceva,
and ONXX's Nexavar, may be affected to a greater degree. In a setting
where both oral and IV drugs are available (such as Revlimid vs. Velcade
for myeloma), the IV drug may become incrementally favored in the
current environment. Additionally, the cost of drugs in settings with more
modest absolute clinical benefit, such as Tarceva in pancreatic cancer
and Nexavar in Asian liver cancer patients, may become incrementally
more difficult to justify.
2
Concerns about impact from the economic cycle arise in part from the high cost of new
cancer drugs. Although economic cycles have not been known to affect the use of drugs for lifethreatening
conditions such as cancer, there has been an escalation of the cost of new cancer
medications. In addition, in recent years payors have implemented new mechanisms to
increasingly shift costs to patients including various deductibles and copays. The current
economic recession also represents the first since the implementation of Medicare Part D. With
the monthly costs of some hematology and oncology drugs reaching above $10,000, even the
catastrophic 5% copay associated with Medicare Part D would equate to $500 in out-of-pocket
expenses for a single drug. Given these considerations, we wondered if the current economic
condition has had a negative impact on the expensive drugs for cancer and hematological
diseases.
Monthly cost of select new drugs for cancer and hematological diseases
Drug Company
Route of
Administration Indication
Year
Approved
Monthly Cost
in US
Revlimid Celgene Oral Multiple Myeloma 2005 $6,500
Tarceva Roche/OSI Oral Lung Cancer 2004 $3,645
Pancreatic Cancer $3,223
Nexavar Onyx/Bayer Oral Renal and Liver Cancer 2005 $5,900
Avastin Roche IV Colorectal Cancer 2004 $5,150
Lung Cancer $10,300
Breast Cancer $10,300
Erbitux IV Colorectal Cancer 2004 $12,300
Head and Neck Cancer
Soliris Alexion IV
Paraoxysmal nocturnal
hemoglobinuria
2007 ~$30,000
Bristol-Myers Squibb
/ Lilly
Source: RedBook, Drug Labels and Company reports
MEDACorp conducted a mini-survey of 79 US medical oncologists and
hematologists/oncologists to assess the impact of the current economic recession on the
use of high-cost drugs for cancer and hematological malignancies. The participating
physicians were based across the US and surveyed from April 2 to April 7, 2009. The consultants
were asked to comment on the impact of the recession on the use of high cost oral and IV
hematology/oncology drugs, the magnitude of any decline, and provide explanations reason for
any decline that that they have observed. The survey was conducted on behalf of a Leerink
Swann analyst and developed by MEDACorp in conjunction with the Leerink analyst.
BIOTECHNOLOGY April 15, 2009
3
Has your use of the following agents been negatively impacted by the economic recession? If you’ve noticed a
negative impact, please indicate the magnitude of said impact. If you do not use a certain agent or group of agents,
please indicate as such.
Yes No
N/A
Overall percent decline in use of
agent due to recession
High-cost oral cancer drugs (i.e., Revlimid, Nexavar, Tarceva) 56% 44% 0% -10.1%
High-cost IV cancer drugs (i.e., Avastin, Erbitux) 52% 48% 0% -8.7%
Soliris 6% 13% 81% -5.5% (n=15)
Source: MEDACorp Survey, Impact of the Economy on the Use of High-Cost Agents, April 2009
MEDACorp survey suggests a noticeable decline in high-cost cancer drug use due to the
recession. More than half (56%) of the 79 surveyed US oncologists and hematologists indicated
that their use of high-cost oral cancer drugs such as Revlimid (CELG), Nexavar (Bayer / ONXX)
and Tarceva (Roche / OSIP) has been negatively affected by the current recession and the
magnitude of this reduction of averaged 10.1% in the entire surveyed sample. Similarly, 52% of
the respondents indicated that their use of high-cost IV cancer drugs such as Roche’s Avastin and
BMY/LLY’s Erbitux was reduced and by an average of 8.7% for all surveyed. Fewer physicians
have had experiences with ALXN’s Soliris and of 15 respondents who have experience with the
drug, 10 indicated no impact from the recession while 5 indicated reduction in use, and the
average decline due to recession for these 15 respondents was estimated to be 5.5%.
The primary driver of the negative impact from current economic conditions appears to be
inability of patients to afford copay. We find explanations provided by the physicians for the
negative impact of the recession particularly interesting to read (the entire survey is attached to
the end of this report). The physician responses to the open-ended question on reasons for
reduction of use clearly indicate that out-of-pocket costs from copays represented a key reason,
and were cited by nearly two thirds (64%) of the 39 respondents providing an explanation. This
was followed by payors becoming more restrictive (21%) and patients losing employment and
insurance (18%). Other reasons cited can be grouped several categories: limited benefit for the
high cost of the drugs as the agents often only provide a short extension of survival (cited by 10%
of respondents); fewer patients treated as oncology practices increasingly try to screen out
patients who cannot afford the drugs (8%); two additional respondents (8%) indicating that some
patients with current employment are refusing and deferring treatment due to concerns that time
off work for treatment may result in the loss of employment, which would be highly undesirable in
the current economic environment. Increasingly poor economics of drugs to the oncology
practices resulting in less drug use was cited by 8% of respondents and high cost of the drugs in
question in general by 5%.
BIOTECHNOLOGY April 15, 2009
4
Physician Responses for Reduced Drug Use
Reasons
# Respondants
Citing
% of Total
Copay 25 64%
Payors becoming more restrictive 8 21%
Patients losing jobs and insurance 7 18%
Limited benefit for the cost 4 10%
Fewer patients treated, general impact on all cancer drugs 3 8%
Patients concerned about losing jobs 2 5%
Poor economics to the practice 3 8%
High cost of the drugs in general 2 5%
Total number of physicians providing an explanation for reduced use 39
Source: MEDACorp Survey, Impact of the Economy on the Use of High-Cost Agents, April 2009
The surveyed sample does not appear to over-represent low-income areas. Since the finding
of a negative economic impact on drugs is relatively novel, we asked if the physicians in our
survey represented a biased sample. One question is whether the surveyed physicians practice
primarily in low-income areas where one might expect a greater impact from the economic cycle
on healthcare. We analyzed the median household income in the zip codes of the practices of the
responding physicians and compared them to the median of the entire country. The results show
the median of household income for the areas where our survey respondents practice was
$50,504, nearly identical to the 2007 US Consensus median household income of $50,233
nationally. In addition, we separated physicians by their responses. The median income for the
areas of the physicians indicating no economic impact is $50,587, numerically slightly higher than
the median income of the areas of physicians indicating a negative economic impact ($45,816).
These analyses suggest that our surveyed sample does not over-represent low-income areas as
compared to national average.
BIOTECHNOLOGY April 15, 2009
5
Median household income of the local areas where surveyed physicians
practice as compared to national median
0
20,000
40,000
60,000
80,000
100,000
120,000
140,000
Respondents
indicating
negative impact
of recession
Respondents
indicating no
impact of
recession
All respondents
Median household income for the zip-code of the
respondent’s practice ($)
median
National
Median
Household
Income
Vertical lines represent the range of incomes in the respective groups, boxes represent income distribution of middle
quartiles and solid horizontal lines represent group median. National Median household median income represented
by grey dashed line (equal to $50,233)
Source: MEDACorp Survey, Impact of the Economy on the Use of High-Cost Agents, April 2009,
www.zipcodes.com, 2007 US Consensus, and Leerink Swann Research
There appears to be a difference in the magnitude of impact on oral vs. IV drugs resulting
from different Medicare coverage. The survey results indicated that oral oncology drugs had a
mean reduction of 10.1% compared to a reduction of 8.7% in IV administered drugs. While the
difference between these estimates may not seem big, the verbal responses from many surveyed
physicians clearly indicated a greater impact from the economic condition on oral drugs compared
to IV drugs. We believe the differential impact can be attributed to the differences in Medicare
policies regarding copay for drugs covered under Medicare Part B (IV drugs) compared to drugs
covered under Medicare Part D (oral drugs).
While both programs require a patient’s copay, the government has authorized supplemental
insurance plans that can cover part to all the out-of pocket copays for Medicare Part B (IV) drugs.
We believe vast majority (80-90%) of patients under Medicare Part B also have supplemental
coverage for the 20% copayment. Similar programs are not authorized and do not exist for oral
BIOTECHNOLOGY April 15, 2009
6
agents covered under Medicare Part D, which can lead to greater out-of-pocket expenses for
patients receiving these drugs. Using 2008 copay scheme as an example, costs for a patient
receiving a Medicare Part D (oral) drug included an initial $275 deductible, after which the patient
would pay 25% of the cost of Part D drugs until the coverage costs of the plan reached $2,510.
Once reached the patients experienced a second deductible called the "donut hole" where
patients are responsible for the full cost of drugs until their total out-of-pocket expenses reach
$4,050. After hitting this level, patient’s payments are reduced to a 5% copay for the remainder of
the calendar year. Because of higher copays under Medicare Part D for oral drugs and our finding
that patient copay is the primary driver for a negative impact from the current economic condition,
we believe it is reasonable to expect a greater impact from the recession on oral drugs compared
to IV drugs.
IMS data also appear to show a more noticeable slow-down of oral vs. IV cancer drugs.
While our survey provides a clear signal of the direction of the economic impact from the
recession, its magnitude may be best understood from national prescription trends and eventually
quarterly sales data. In the following charts, we plotted the total monthly prescriptions (TRx) from
IMS for several newer oral cancer drugs. We believe the TRx data are relatively accurate for
which such data are available (for certain drugs like Nexavar, prescription data are withheld from
IMS at the request of the manufacturer). While the situation of each drug differs and depends on
many other factors such as competition and it is difficult to draw a sweeping general conclusion, 4
of the 5 drugs that we looked at (PFE’s Sutent, Roche/OSIP’s Tarceva, GSK’s Tykerb, and
Roche’s Xeloda) all appear to show declining trends in recent months. Even for the 5th agent
(NVS’s Gleevec), there appears to be a slow-down in recent months in script trends as compared
to periods before. For IV cancer drugs which can be tracked (imperfectly) with IMS reported
monthly sales data, this break in recent trends is not as noticeably. However, IMS sales data likely
took into consideration price increases which may have masked any decline in volume.
BIOTECHNOLOGY April 15, 2009
7
Total Monthly Prescription Trends of Oral Cancer Medications
GLEEVEC NVR 052001
0
5,000
10,000
15,000
20,000
25,000
Mar-06
Jun-06
Sep-06
Dec-06
Mar-07
Jun-07
Sep-07
Dec-07
Mar-08
Jun-0 8
Sep-08
Dec-08
Total monthly prescriptions
(TRx)
SUTENT PFZ 022006
0
1,000
2,000
3,000
4,000
5,000
Mar-06
Jun-06
Sep-06
Dec-06
Mar-07
Jun-07
Sep-07
Dec-07
Mar-08
Jun-08
Sep-08
Dec-08
Total monthly prescriptions
(TRx)
TARCEVA GTC 112004
0
2,000
4,000
6,000
8,000
10,000
12,000
14,000
Mar-06
Jun-06
Sep-06
Dec-06
Mar-07
Jun-07
Sep-07
Dec-07
Mar-08
Jun-0 8
Sep-08
Dec-08
Total monthly prescriptions
(TRx)
TYKERB GSK 032007
0
500
1000
1500
2000
2500
Mar-06
Jun-06
Sep-06
Dec-06
Mar-07
Jun-07
Sep-07
Dec-07
Mar-08
Jun-08
Sep-08
Dec-08
Total monthly prescriptions
(TRx)
XELODA ROC 051998
0
5,000
10,000
15,000
20,000
25,000
30,000
Mar-06
Jun-06
Sep-06
Dec-06
Mar-07
Jun-07
Sep-07
Dec-07
Mar-08
Jun-08
Sep-08
Dec-08
Total monthly prescriptions
(TRx)
Source: IMS Health
BIOTECHNOLOGY April 15, 2009
8
Monthly IMS Sales Trends for IV Cancer Medications
AVASTIN GTC 032004
0
50
100
150
200
250
300
Mar-06
May-06
Jul-06
Sep-06
Nov-06
Jan-07
Mar-07
May-07
Jul-07
Sep-07
Nov-07
Jan-08
Mar-08
May-08
Jul-08
Sep-08
Nov-08
Jan-09
IMS Sales ($MM)
ERBITUX ISY 022004
0
10
20
30
40
50
60
70
80
90
Mar-06
May-06
Jul-06
Sep-06
Nov-06
Jan-07
Mar-07
May-07
Jul-07
Sep-07
Nov-07
Jan-08
Mar-08
May-08
Jul-08
Sep-08
Nov-08
Jan-09
IMS Sales ($MM)
HERCEPTIN GTC 101998
0
20
40
60
80
100
120
140
Mar-06
May-06
Jul-06
Sep-06
Nov-06
Jan-07
Mar-07
May-07
Jul-07
Sep-07
Nov-07
Jan-08
Mar-08
May-08
Jul-08
Sep-08
Nov-08
Jan-09
IMS Sales ($MM)
RITUXAN GTC 121997
0
50
100
150
200
250
Mar-06
May-06
Jul-06
Sep-06
Nov-06
Jan-07
Mar-07
May-07
Jul-07
Sep-07
Nov-07
Jan-08
Mar-08
May-08
Jul-08
Sep-08
Nov-08
Jan-09
IMS Sales ($MM)
TAXOTERE S.A 061996
0
20
40
60
80
100
120
Mar-06
May-06
Jul-06
Sep-06
Nov-06
Jan-07
Mar-07
May-07
Jul-07
Sep-07
Nov-07
Jan-08
Mar-08
May-08
Jul-08
Sep-08
Nov-08
Jan-09
IMS Sales ($MM)
VELCADE MNN 052003
0
5
10
15
20
25
30
35
40
45
Mar-06
May-06
Jul-06
Sep-06
Nov-06
Jan-07
Mar-07
May-07
Jul-07
Sep-07
Nov-07
Jan-08
Mar-08
May-08
Jul-08
Sep-08
Nov-08
Jan-09
IMS Sales ($MM)
ELOXATIN S.A 092002
0
20
40
60
80
100
120
140
160
Mar-06
May-06
Jul-06
Sep-06
Nov-06
Jan-07
Mar-07
May-07
Jul-07
Sep-07
Nov-07
Jan-08
Mar-08
May-08
Jul-08
Sep-08
Nov-08
Jan-09
IMS Sales ($MM)
Source: IMS Health
BIOTECHNOLOGY April 15, 2009
9
IMPACT OF THE ECONOMY ON THE USE OF HIGH-COST AGENTS
Respondent Distribution
Specialty Medical Oncology and Hematology
Geographic Distribution
Products High-Cost Cancer Agents
Number of Consultants 79 Oncologists and Hematologists
Respondent Distribution United States
Survey Date April 2009
Responses represent an average of the aggregate response (n=79) unless otherwise noted.
Survey Purpose
This survey is designed to analyze whether the current state of the economy is impacting the use of various high-cost agents.
Overall Trends in High-Cost Agent Utilization
1. Has your use of the following agents been negatively impacted by the economic recession? If you’ve noticed a negative
impact, please indicate the magnitude of said impact. If you do not use a certain agent or group of agents, please indicate as
such.
Yes No
N/A
Overall percent decline in use of
agent due to recession
High-cost oral cancer drugs (i.e., Revlimid, Nexavar, Tarceva) 56% 44% 0% -10.1%
High-cost IV cancer drugs (i.e., Avastin, Erbitux) 52% 48% 0% -8.7%
Soliris 6% 13% 81% -5.5% (n=15)
If you’ve noticed a negative impact, due to the recession, to your use of any of the above listed agents, please explain.
Please see Appendix I for a summary of consultants’ responses.
BIOTECHNOLOGY April 15, 2009
10
Appendix I. Summary of consultants’ responses.
Question 1: If you’ve noticed a negative impact, due to the recession, to your use of any of the above
listed agents, please explain.
3 Some patients with more concern on impact of copays, etc.
5
Have noticed an impact due to recession for all of the above agents. Patients can not afford
copays.
6
We used to use high cost biologics loosely until we discovered that patients cannot afford to pay
their copay and therefore we were losing. So we decided to abide by published data when it
comes to biologics and restrict their use and use less costly equally effective regimens. We
have therefore developed our own guidelines to treat patients that follow the rule: 1/ data, 2/
least toxic and 3/ least costly. We have also been proactive in checking credit history on our
patients and asking for payments upfront if their credit history is not good. We have not been
allowing patients to get their next cycle of chemo if they have an unsettled balance.
12 Patients don’t have disposable income and also many have lost insurance and drug plans
13
The recession is impacting all now and even the generics. Soliris has not yet been hit but its
use is very limited.
17 Have had occasional patients request to stop drug due to high out-of-pocket costs
18
Have had more issues with insurance companies and reimbursement since downturn in
economy than ever before
19 No copay
20 People are not willing to pay for drugs with no curative benefit
21 Patients are more reluctant to lay out cash and are also worried about losing their jobs
22 The recession has indirectly affected drug costs, reimbursements. Tighter margins.
24
All depends on: a) copays, b) open and frank discussion about copays, c) cost/benefit issues
now include financial toxicity! I only have one patient on Soliris at this time, so no change for
that agent.
27 Third party payers have become quite strict on the use of these agents.
29 Harder to afford copays and deductibles
30
Patients are less likely to consider high cost drugs given the fact some of the drugs can only
marginally improve the survival benefit. The cost-effectiveness is not positive for some of the
drugs both from physicians’ view and patients’ view. There is a lot of work to do to identify who
will benefit from these drugs the most and justify the high cost.
31 Patients are reluctant or unable to pay share of cost/copay
32 More patients are unable to pay for oral drugs
33 Patients are refusing treatments or delaying, causing a decrease in patient flow and revenue
34
Greater difficulties in reimbursement IV drugs. Patients refuse to spend lots of money for oral
drugs.
35
No impact yet, but I should note that’s probably partially because we have a social worker that
helps with this.
36 Patients have opted for no treatment due to cost
39
Most patients have insurance and don’t have to pay the total cost of the drug but it is a situation
that continues to be watched
40
Oral drugs often have a higher out of pocket expense for patients, and with economic changes it
is difficult for many patients to make the copays. I only have one patient getting Soliris and so
far the economy has not affected him.
41
Acquisition cost is too high for a solo oncology practice, especially with poor payment practices
by insurers.
42
The insurance is reluctant to cover the cost of drug; physicians are looking for alternatives; profit
is minimal
43
Decline with oral meds - I try to get them through indigent program with the company, but still
there is some decrease in the use if a pt has to pay a copay due to the economy. With IV meds,
usually pts are sent to the hospital outpt. for that, so no change.
44 Less ctx use and above.
47 Lots of patients losing insurance coverage.
BIOTECHNOLOGY April 15, 2009
11
48
Patients losing their insurance. Patients not able to pay for COBRA. Patients losing their
Medicare part D. Patients not willing to undergo prolonged chemotherapy due to fear of losing
their jobs due to constant time off. Insurance tightening approval of on-label but not line of
therapy.
50
Oral agents are expensive and cost with the paperwork is a barrier for patients and physicians.
For IV drugs, no burden to patient as no out of pocket cost, so no change.
51 More people cannot afford oral medications, more people with no insurance or high copays
54 Unable to afford copays
57
Patients are more reluctant to accept a marginal benefit for some drugs with a high copay. We
have not seen this yet in IV medications, but I think it will be coming soon for some.
58 Patients have lost health insurance or can no longer afford the copay
59
Patients have less insurance and money for copays - worried about going broke paying for
healthcare
62 Patients cannot afford copays associated with the above drugs
65 Copay issues, strict insurance companies
66
I am concerned this may happen soon as some of my pts. are losing their insurance, but so far I
have not had a significant problem.
67
The insurance companies are getting very tight in their approval of the above drugs and have
added many requirements to some of them. Patients also are often unable to make copayments
and patient assistance programs are not always able to help.
75
Oral drugs generally have a much higher patient out-of-pocket responsibility and are thus more
sensitive to patients’ ability to pay for them directly.
76 Fewer patient with insurance and fewer patient able to afford copays
77 Patients have harder time to meet their copayments.
79
Copays on oral drugs are very expensive, so patients are opting to settle for less effective
therapy to save money. This issue has made an impact in the way we treat certain solid tumors
and heme. malignancies
BIOTECHNOLOGY April 15, 2009
12
Disclosures Appendix
Analyst Certification
I, Howard Liang, Ph.D., certify that the views expressed in this report accurately reflect my views and that no part of
mycompensation was, is, or will be directly related to the specific recommendation or views contained in this report.
Distribution of Ratings/Investment Banking Services (IB) as of 03/31/09
IB Serv./Past 12
Mos.
Rating Count Percent Count Percent
BUY [OP] 80 62.02 6 7.50
HOLD [MP] 45 34.88 2 4.44
SELL [UP] 4 3.10 0 0.00
Explanation of Ratings
Outperform (Buy): We expect this stock to outperform its benchmark over the next 12 months.
Market Perform (Hold/Neutral): We expect this stock to perform in line with its benchmark over the next 12
months.
Underperform (Sell): We expect this stock to underperform its benchmark over the next 12 months.
The degree of outperformance or underperformance required to warrant an Outperform or an Underperform
rating should be commensurate with the risk profile of the company
For the purposes of these definitions the relevant benchmark will be the Russell 2000® Health Care Index
for issuers with a market capitalization of less than $2 billion and the S&P 500® Health Care Index for
issuers with a market capitalization over $2 billion.
Definitions of Leerink Swann Ratings prior to October 1, 2006 are shown below:
Outperform (Buy): We expect this stock to outperform its benchmark by more than 10 percentage points
over the next 12 months.
Market Perform (Hold/Neutral): We expect this stock to perform within a range of plus or minus 10
percentage points of its benchmark over the next 12 months.
Underperform (Sell): We expect this stock to underperform its benchmark by more than 10 percentage
points over the next 12 months.
For the purposes of these definitions the relevant benchmark will be the Russell 2000® Health Care Index
for issuers with a market capitalization of less than $2 billion and the S&P 500® Index for issuers with a
market capitalization over $2 billion.
BIOTECHNOLOGY April 15, 2009
13
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©2009 Leerink Swann LLC. All rights reserved. This document may not be reproduced or circulated without
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BIOTECHNOLOGY April 15, 2009
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Protellos five year data
The Strength Of Strontium Ranelate - Protects Bones For At Least Five Years, Remodels Bone Architecture
05 Jun 2006
In previous clinical trials strontium ranelate has proven effective in preventing fractures for up to three years. But according to new data presented today at the IOF World Congress on Osteoporosis in Toronto, Canada that window of opportunity can now be extended to at least five years.
Jean-Yves Reginster, Professor of Epidemiology, Public Health and Health Economics at the University of Liege, Belgium, reported (see conference Abstract No. OC24) that in the phase III Spinal Osteoporosis Therapeutic Intervention (SOTI) trial, strontium ranelate reduced the risk of new vertebral fractures by about 30 percent over four years. In the Treatment Of Peripheral Osteoporosis (TROPOS) trial, which has been running a little longer, those taking the drug for five years had about a 25 percent reduction in vertebral fractures and a 15 percent reduction in non-vertebral fractures, such as those of the thigh. �These results demonstrate, uniquely for anti-osteoporotic treatments, that strontium ranelate provides sustained efficacy over five years against both vertebral and non-vertebral fractures,� said Reginster.
Because other existing treatments have not demonstrated such robust effects in prospective, pre-planned, double-blind, placebo-controlled studies, postmenopausal osteoporotic women stand to benefit from the proven efficacy and tolerability of strontium treatment, according to Reginster.
In two other studies presented at the IOF WCO this week, Georges Boivin and colleagues at the INSERM, Universite Claude Bernard, Lyon, France and J. Yebin Jiang and colleagues at the University of California and the University of Michigan Osteoporosis and Arthritis Lab report on just how strontium ranelate contributes to bone strength.
Boivin (see conference Abstract No. P310) reported that strontium is incorporated into new bone but does not make its way into older bone, which remains virtually free of strontium even after three years of treatment. His findings, based on high resolution X-ray microanalysis, also suggests that strontium does not affect the quality of the bone mineral, but it does affect the quantity. �We believe that the microarchitecture of bone is improved in those taking strontium ranelate. It appears that the bone mass is increased with a normal degree of mineralization,� said Boivin. The best way to think of this is to imagine bone as a tube filled with styrofoam packing. On strontium ranelate, the nature of the packing does not change, but the amount of packing and how it fits together does.
That theory is supported by the findings of Jiang and colleagues, who reported (see conference Abstract No. OC40) that strontium does, in fact, rearrange bone architecture. Bone is made up of two different types of structure, a spongier honeycomb core and a harder outside layer called cortical bone. Jiang reported that the bone making up the honeycomb appears as flatter, plate-like mineral in samples taken from patients treated with strontium ranelate, whereas in control samples the bone appears as rod-like structures. He also reported that the outer cortical bone becomes thicker. �The three-dimensional changes in trabecular and cortical bone may improve bone mechanical strength, explaining the decreased risk for fracture in those on strontium ranelate treatment,� said Jiang.
Both groups obtained their data by analyzing biopsies taken from those enrolled in the TROPOS, SOTI and also the STRATOS phase II clinical trials for strontium ranelate. Boivin and colleagues used high resolution X-ray microradiography to determine the degree of mineralization of pelvic bone samples. Jiang and colleagues used a sophisticated micro computerized tomography scanner, better known as a micro CAT scanner, to measure the three-dimensional structure of the bone, also taken from the pelvis. Boivin compared 35 samples taken from patients treated with various doses of strontium ranelate, with 22 samples taken from those given placebo. Jiang and colleagues measured similar numbers of samples, 20 from the treatment group and 21 controls.
Bisphophonates - Medicine that Keeps on Giving
Boivin's findings also suggest that because strontium is laid down at the surface of newly formed bone mineral, it may be rapidly cleared from the bone once treatment is stopped. Bisphosphonates, on the other hand, are released only very slowly from bone and continue to appear in the urine for years after treatment is stopped according to researchers from the Netherlands (see conference Abstract No. OC25). The finding should caution against prescribing the drugs for young girls who suffer from osteoporosis or brittle bone disorders such as osteogenesis imperfecta.
Bisphosphonates are the most widely prescribed treatment for those with, or at risk for, osteoporosis. Like strontium, bisphosphonates are incorporated into bone where they stop the bone mineral from being dissolved away. They are known to be slowly released from bone but just how long they remain imbedded in the mineral is uncertain. However, at the IOF WCO, Socrates Papapoulos and colleagues at Leiden University, report that the bisphosphonate pamidronate can still be detected in urine eight years after treatment has stopped.
�Up to now it has been hypothesized in the literature that bisphosphonates trapped in the bone are slowly released once therapy is stopped, but now we show for the first time that that phenomenon is real,� said Papapoulous.
The researchers tested urine samples from 6 children who had been given pamidronate for 4-10 years. Urinary measurements were taken up to 13 years after treatment was suspended. Pamidronate was measurable in urine of all patients except one, who had received treatment for 6 years, and drug was measured 13 years after stopping treatment.
The long half-life of bone bisphosphonates probably explains why osteoporotic women who have taken bisphosphonates for a long time have reduced bone mineral loss after stopping treatment. But there is a small cloud to this silver lining-�we need to be cautious about administering bisphosphonates to young girls because there is very little data on the effects of these drugs on embryonic development,� said Papapoulous.
Combination Therapy Packs One-Two Punch
Silvano Adami, University of Verona, Italy, and colleagues reported that women who have completed a course of another hormone therapy, parathyroid hormone, maintain better bone strength if they begin taking the Selective Estrogen Receptor Modulator (SERM) raloxifene once the parathyroid treatment has ended (see conference Abstract No. OC22).
�The results tell us that after a course of parathyroid treatment it is important to begin taking an anti-resorber, such as raloxifene, as soon as possible,� said Adami.
Parathyroid hormone is one of very few therapies that actually stimulates bone formation but the treatment is limited to two years or less in most countries. This has left doctors and patients wondering what the best course of action is once the hormone therapy has ended. SERMs are compounds that mimic only some of the action of estrogen. As such, they have different efficacies and side effects to hormone replacement therapy.
Adami and colleagues measured bone mineral density in 329 women who had been on parathyroid for one year then switched to either raloxifene or a placebo for a subsequent year. The researchers found that at the end of the second year, women who followed the parathyroid therapy with the estrogen mimic had a 2.3% higher bone density at the hip than those who had taken a placebo after the hormone treatment.
The researchers are planning to continue this study to see how long the benefit of the sequential parathyroid/raloxifene therapy persists.
Problems with New Hormone Replacement Therapy
In the recent LIFT trial to measure the efficacy of the estrogen hormone replacement therapy tibolone. Steve Cummings, Director of the San Francisco Coordinating Center, University of California, San Francisco and lead investigator, reported that follow up analysis showed that women who had taken the drug had about half as many vertebral fractures as those who had taken placebo (see conference Abstract No.OC38).
However, this trial was halted due to increased incidence of stroke. �The increased risk of stroke was unexpected and will limit the use of tibolone for prevention of osteoporosis and fracture,� said Cummings. He also suggested that women and physicians should weigh the benefits and risks and consider alternatives before prescribing tibolone for any indication.
Osteoporosis, in which the bones become porous and break easily, is one of the world's most common and debilitating diseases. The result: pain, loss of movement, inability to perform daily chores, and in many cases, death. One out of three women over 50 will experience osteoporotic fractures, as will one out of five men 1, 2, 3. Unfortunately, screening for people at risk is far from being a standard practice. Osteoporosis can, to a certain extent, be prevented, it can be easily diagnosed and effective treatments are available.
The International Osteoporosis Foundation (IOF) is the only worldwide organization dedicated to the fight against osteoporosis. It brings together scientists, physicians, patient societies and corporate partners. Working with its 170 member societies in 84 locations, and other healthcare-related organizations around the world, IOF encourages awareness and prevention, early detection and improved treatment of osteoporosis.
1 Melton U, Chrischilles EA, Cooper C et al. How many women have osteoporosis? Journal of Bone Mineral Research, 1992; 7:1005-10
2 Kanis JA et al. Long-term risk of osteoporotic fracture in Malmo. Osteoporosis International, 2000; 11:669-674
3 Melton LJ, et al. Bone density and fracture risk in men. JBMR. 1998; 13:No 12:1915
IOF World Congress on Osteoporosis, held every two years, is the only global congress dedicated specifically to all aspects of osteoporosis. Besides the opportunity to learn about the latest science and developments in diagnosis, treatment and the most recent socio-economic studies, participants have the chance to meet and exchange ideas with other physicians from around the world. All aspects of osteoporosis will be covered during the Congress which will comprise lectures by invited speakers presenting cutting edge research in the field, and 35 oral presentations and more than 680 poster presentations selected from 720 submitted abstracts. More than 70 Meet the Expert Sessions covering many practical aspects of diagnosis and management of osteoporosis are also on the program.
For more information on osteoporosis and IOF please visit:
http://www.osteofound.org
Osteologix OLGX important info about phase 3
one phase 3 trial makes this easier to partner
We are designing our development plan for NB S101 for osteoporosis to comply with both U.S. and European guidelines. On February 17, 2009, we held a meeting with the FDA regarding the proposed development of NB S101. Based on feedback from the FDA meeting, we believe that the continued development of NB S101 will require an additional phase II trial and only one large, well-controlled phase III trial.
The FDA and EMEA require positive results from phase III studies before they will approve an NDA. In order to obtain approval for a new drug for the treatment of osteoporosis, current regulatory guidelines require placebo-controlled double-blind studies with fracture reduction as the primary endpoint. An adequate fracture-prevention trial represents a significant time and resource investment, as the treatment duration in the required clinical studies can be up to three years, although recent trials have been conducted with a two-year treatment duration and more recently an advisory group has recommended that these trials be reduced to 18 to 24 months in duration. These trials raise ethical questions concerning the use of placebo groups when approved drugs are available to treat osteoporosis, and both European and U.S. regulatory authorities are currently debating whether continued use of such trials can be recommended. If future guidelines prevent or limit the use of placebo control in such studies, we may plan to alternatively conduct a non-inferiority study against an established osteoporosis treatment or otherwise modify our plans based on any new guidelines established for approval of drugs to treat or prevent osteoporosis.
Based on the current FDA and EMEA guidelines and anticipated changes, we anticipate the primary objective of a phase III study will be to evaluate the ability of NB S101 to prevent incident vertebral fracture. We also anticipate that we would collect data on non-vertebral fractures, spine, hip and forearm BMD, and biochemical markers of bone and cartilage turnover. We estimate that the phase III study may enroll up to 3,000 osteoporotic women, comparing one dose of NB S101 to placebo over a two- to three-year treatment period, with a possible two-year extension. Based on continuing analysis of the phase II data and discussions with regulatory agencies, we are continuing statistical assessments before we finalize any phase III clinical trial design and determine the specific number of patients needed.
http://www.sec.gov/Archives/edgar/data/1...
page 9
OSTEOLOGIX (OLGX) this company has what appears to be a better drug than Protelos which is selling at a run rate of 300 million a year in Europe. It is over 60 percent owned by Nordic Biosciences, which is why the stock is so thinly traded. If you can build a position I believe there is huge upside.
Osteologix Announces Win Versus Opposition for its European Patent
Covering NBS-101 for Osteoporosis – Reiterating Buy on OLGX.
Highlights
• Osteologix wins in patent dispute in Europe as its NBS-101 patent is upheld by
the European Patent Office (EPO). We believe the upholding of the patent by the
EPO represents an important victory for Osteologix for a number of reasons
including: First, it validates the potential value of the product for a partnership in
Europe. Second, it validates the findings of enhanced bioavailability (BA) with the
malonate salt were not “obvious”. In other words, the EPO found, since the
malonate salt is not widely used or a well know salt in drug formulation and it has not
already been shown to demonstrate an increase in BA for a wide range of
compounds, it was not “obvious” malonate would increase BA. Third, the EPO
agreed malonate salt definitely increased BA. Fourth, it increases our confidence for
the issuance of the patent in the US by the USPTO. We expect the USPTO could
complete its review of the patent by 2Q 2009 and the issuance of the patent in the
U.S. would represent an important catalyst for the Company and its partnership
prospects for the product. For background on this patent: In May of 2003
(International filing date May 2004), Osteologix filed in the EU a patent entitled
“Water-soluble strontium salts for use in treatment of cartilage and/or bone
conditions” which protects strontium salts with specific water solubility profiles,
excluding strontium ranelate. The EPO issued this patent, European Patent # EP-
1,534,305B9, in October 2006, with an expiration date in May 2024. However, in
July 2007, Intellectual Property Services of Paris, France filed a Notice of Opposition
against Osteologix’s European Patent requesting the EPO revoke the entire patent.
Importantly, Osteologix conducted a wide series of chemical modeling and animal
tests to fully define the ideal solubility profile and to optimize the BA of strontium
using a wide variety of organic and inorganic salts. From this testing they identified
strontium malonate as the most ideal salt for development as an oral drug. They
also conducted a number of human clinical trials including Phase I PK/PD studies
and a Phase II trial demonstrating efficacy. Importantly, OLGX also filed IP
surrounding combination use of strontium with other therapies, and have
applications related to manufacturing, osteonecrosis, and arthritis.
As of September 30, 2008 Osteologix had $5.3 million in cash. We believe
Osteologix $5.3 million in cash as of September 30, 2008 represents sufficient cash
to design a Phase III program, continue work on the IP issuance and continue
negotiating with potential partners. We believe Osteologix could need to raise
additional capital to show strength to potential partners in order to maximize the
value of their asset.
• We reiterate our BUY rating. We continue to believe Osteologix represents a
unique opportunity to invest in a late-stage compound which addresses a large
indication at a very attractive valuation. Additionally, we believe USPTO action on a
key patent for the company expected during 2Q 2009 and confirmation of the
regulatory pathway from FDA expected later this year could serve as important
catalysts for OLGX.
Long-term (8 year) data for strontium ranelate (Protelos) detail the positive efficacy data for 893 patients.
Patients from two double-blind, placebo-controlled, five-year Phase III trials (SOTI Study and the TROPOS Study),
which included a total of 6740 postmenopausal women with osteoporosis, were enrolled into a three-year openlabel
extension study. All Protelos treated patients received 2g per day. The efficacy data clearly indicate bone
mineral density (lumbar >25% increase and femoral neck >10% increase) increased continuously during the study
in Protelos treated patients. Additionally, the cumulative incidence of vertebral (14.9% yrs 1-3 vs 13.7% yrs 5-8)
and non-vertebral (11.2% yrs 1-3 vs 12% yrs 5-8) fractures remained unchanged during the three year extension
study from the first three years of the controlled trials. We are impressed with BMD and fracture incidence results
as they verify the durability of Protelos’ efficacy and because they occurred despite an increased risk associated
with aging Protelos treatment
during the 3 year open label extension study mitigates an increase in vertebral or non-vertebral fracture rates as
the cumulative fracture incidence remained stable/unchanged during the three year extension study when
compared to the incidence observed during the first three years of the placebo-controlled phase in the SOTI and
TROPOS trials. We are impressed with BMD and fracture incidence results as they verify the durability of Protelos’
efficacy and they occurred despite an increased risk associated with aging.
Protelos sales have rebounded and continue to grow following reports of anaphylactic reactions during 4Q
2007. Strontium ranelate continues to show sales growth in Europe (we believe revenues are at >$300 million
annual run rate), being very strong in new markets, with moderated growth in certain countries. The rebound in the
revenue ramp during 2Q 2008, supports our belief that physicians will view the potential for anaphylactic reactions
essentially as a non-issue which must be monitored for and is addressable by discontinuation of therapy. The rate
of observed anaphylactic reactions is lower than that seen with several other approved drugs. We continue to
believe the occurrence of DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) associated with
strontium ranelate may be associated with the synthetic ranelate salt which is not used in any other therapeutic
agent. Investors should remember that NBS-101 is strontium malonate which is a naturally occurring salt used in a
couple other approved drugs.
Upcoming Milestones Product Event Timing
NBS-101 FDA regulatory meeting, Pre-Phase III 1Q 2009
NBS-101 Initiate Phase III program 2009
NBS-101 Partnership 2009
NBS-101 Action on Key IP by USPTO 2Q 2009
Osteologix reported 4Q 2008 results with a lower burn than expected. The
Company reported a net loss of $1.1 million, or ($0.04) per share versus our estimate of
a net loss of $1.8 million, or ($0.06) per share. Overall, the Company has a burn rate of
approximately $350,000 per month resulting in expenses which were $0.7 million lower
than our estimate. The lower expenses are largely due to a lower than estimated R&D
and SG&A expenses. We project 2009 operating expenses to be lower than 2008 with
R&D expenses of $1.65 million and SG&A expenses of $2.6 million. Additionally, based
on the status of the IP in the US and Europe combined with the Company’s ongoing
interaction with the FDA, we project OLGX could sign a partnership for NBS-101 by late
2009/early 2010. Further, we believe a number of catalysts expected during the next
three quarters including: of patent issuance by the USPTO for NBS-101; conclusion of
discussions with the FDA regarding the appropriate design of Phase III trials; and a
potential corporate partnership for NBS-101, could serve as important drivers for the
stock.
As of December 31, 2008 Osteologix had $4.4 million in cash. We believe
Osteologix $4.4 million in cash as of YE 2008 represents sufficient cash to design a
Phase III program, continue work on the IP issuance and continue negotiating with
potential partners. We believe Osteologix could need to raise additional capital to show
strength to potential partners in order to maximize the value of their asset.
• We reiterate our BUY rating. We continue to believe Osteologix represents a unique
opportunity to invest in a late-stage/Phase III-ready compound which addresses a large
indication at a very attractive valuation. Additionally, we believe USPTO action on a key
patent for the company expected during 2Q 2009 and confirmation of the regulatory
pathway from FDA expected later this year could serve as important catalysts for
OLGX.
Dendreon gave absolutely no data. They are keeping it under wraps for the AUA meeting.
Companies usually give some data, even though they are going to give more detail at an upcoming meeting. Everyone says if they didn't meet the endpoint they will go to jail.
I haven't seen the CEO or anyone else at GTC Biotech go to jail even though they met the endpoint, until they didn't. It was just a different interpretation of the data.
That could be what we have here. What is adding to my skepticism is the fact that they aren't filing the NDA until the 4th quarter. This is an open NDA, so all of the modules are already complete. All they have to do is insert the data from this trial. The rest of the NDA is already done. When companies delay the NDA it is usually because the longer they delay it, the longer the stock can stay afloat, because the longer the rejection is delayed.
I didn't have a position either way, I hope the data is great but I have a feeling that it isn't overwhelming even if it met the endpoint.
Dendreon to disclose Provenge data for prostate cancer Tuesday
Dendreon said it will disclose Tuesday the results of a long-awaited clinical trial of Provenge, its immunotherapy treatment for advanced prostate cancer.
By Seattle Times business staff
Dendreon, perhaps Seattle's most-watched biotechnology company at the moment, said Monday it will hold a conference call at 6 a.m. Seattle time Tuesday to disclose the long-awaited results of a final clinical trial for its treatment of advanced prostate cancer.
Dendreon's shares have jumped 113 percent in the past month as speculation intensified over the final results of the study, known by its acronym IMPACT.
Provenge, Dendreon's lead therapy, could be the first commercial immunotherapy to fight prostate cancer, if approved.
In early April Dendreon shares rose 38 percent, the most in two years according to Bloomberg News, after the company reserved conference space in case it wanted to present data at the American Urological Association on April 28. Analysts pointed out that any data reported at the conference could be positive or negative.
The company's efforts to gain FDA approval for Provenge have been marked by repeated setbacks.
Interim results reported in October "did not meet the pre-specified criteria" for Dendreon to update the approval application it had pending at the FDA, said Chief Executive Mitch Gold in a conference call at the time. The drug showed a 20 percent increase in survival rates among patients using Provenge, but to meet the study goals, the company needed to show a 22 percent drop in the risk of death based on 304 patients, according to a Seattle Times report.
In early 2007, the company stock rode as high as $19 on hopes that the FDA would approve the product that May.
But the agency decided to withhold approval, asking for more data instead. That triggered a sharp fall in the stock price and an angry response from patients eager for a promising treatment.
Copyright © 2009 The Seattle Times Company
actually the guys in seattle know the answer so they are writing the script for tomorrow
eating private provenge
Why Does US Healthcare Cost So Much?
because we allow a company like Alexion charge 450k a year for a drug that cost the company less than 20 million to develop.
because cancer drugs cost 50 to 100k a year to increase lifespan by weeks, and most of the time increases toxicity.
that is why
I know the market will figure it out within ten seconds because if the don't say the hit the primary endpoint in the title it failed.
it is just that you congratualted the guy on his short which means you definitely feel it failed.
DNDN: If the trial misses I'm sure Croumagnon sold today and he will tell us tomorrow after the conference call.
If it works he will say he owns it but if it fails he will not post
I am not in dndn, but I do not think it is neccessarily bad news that they are holding the call tomorrow without releasing news
do you think they want to hold the call at 9 so that the market can't digest the data in the way they will spin it?
I just didn't think it would work because the data hasn't shown that it would but I am not basing it on the time of the news and cc.