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Of course MNTA looked at many batches of Copaxone to ensure their version is not too different (between and within batches of their own product and of reference standards - the branded), I don't believe they would have submitted an ANDA without that. However, they cannot show pharmacokinetic properties (no detectable serum levels, no activity test, no biomarker, no proven MoA), and prove their product is as safe and active. Showing sameness with biochemical analytical lab tools won't be enough to satisfy the FDA in this case, they need to show bioequivalence and this will require clinical studies, imo.
In the process of making Copaxone you need to create the polypeptides of the mixture. During the polymerization the order of adding the four amino acids is important and so is the ratio. Even if replicated and the formulation contains the necessary components, in the same amounts, it may not be in the same sequence proportions. Change one bit and the process yields different polymers of differing sequence. So, if you don't know all steps of the original process you need to reverse engineer it. This is far more difficult than purification and analysis of sugars. MNTA has reverse engineer the Copaxone production process but I believe they will have to prove they end up with an identical product.
There are many complicating factors with Copaxone that I don't think a generic can be proved identical in the way small molecule generics do. Its complexed formulation - a mixture of synthetic polypeptides containing random sequences (of 4 amino acids) of varying lengths and ratios, makes showing that you have the identical mix in the soup not good enough. You also need to show that the composition of your product is the same because it may vary depending on how it is formulated and polymerized. Attempting to replicate such random formulation might result in hight variability and with the current FDA environment it is very likely they will require clinical work and perhaps specific requirements such as switching studies,imho.
How would MNTA prove the generic product is identical without conducting trials?
Accepting does not mean clinical trials will not be required.
Complex generics like enoxaparin and glatiramer acetate were submitted and accepted for review under the existing ANDA pathway because there isn't a specific pathway for biosimilars yet. Such legislation is expected in the near future but meanwhile the FDA cannot treat these as standard chemical. Copaxone is more of a biologic drug because its formulation and manufacture are very complexed, its precise MoA has never been fully characterized nor confirmed, after being injected it degrades to small peptides and free amino acids locally, so serum concentrations are too low to be detected (it is not even clear if they need to be in the systemic circulation for their effects), and there isn't any way (test or model) to prove its activity except for clinical trials. I do appreciate Momenta's tech a lot and think it is capable of reverse engineering Copaxone correctly. However, they will have to show safety and efficacy via clinical trials, imo.
Teva at risk launches
On Lotrel - Par's settlement with NVS is a significant positive for Teva, which has the only generic on the market (except for Sandoz's authorized).
On Protonix - Wyeth's preliminary injunction was rejected and Teva's obviousness arguments might even win the litigation but even if Teva loses, the risk is much lower than it seemed (probably single not treble damages).
Gemzar is a potential for at risk launch by Teva.
Teva is concerned about generic Copaxone alright, or else why would it start the SONG and GALA studies?
Teva must diversify away from Copaxone regardless of the generic threat and they know it. Nevertheless, even if Teva loses the patent case in court, odds for generic Copaxone to be approved without clinical trials are close to zero, imo, so this is still a few years away.
One note is that Ratiopharm has capability for biogenerics via its daughter company - BioGeneriX, which has a filgrastim biosimilar (Ratiograstim) product on the market and several more in the pipeline.
It's official now and Teva (stock is up 4% here) paid €3.625B:
http://www.globes.co.il/serveen/globes/docview.asp?did=1000547810&fid=942
On the flip side of RAF inhibitors:
Editor's Summary 18 March 2010
Mixed signals from RAF
Abnormal activation of the RAS-RAF-MEK-ERK signalling pathway is a feature of many human cancers, making it an attractive target for antitumour therapy. Several RAF and MEK inhibitors are in clinical trials, but an unexpected complication has emerged. Although selective BRAF inhibitors are effective in treating mutant BRAF melanoma, in which they potently suppress RAF-MEK-ERK signalling, the same inhibitors are ineffective against tumours that carry an oncogenic mutation in the KRAS gene. Two groups now report that the reason for this dramatic difference is that RAF 'inhibitors' have dual activity, functioning as either inhibitors or activators of RAF, depending on the cellular context and mutational status of RAF. In News & Views, Karen Cichowski and Pasi Jänne discuss the mechanistic and clinical implications of these findings and similar work reported in Cell.
Cancer - thinking outside the box
The Mathematics Of Cancer
http://www.forbes.com/forbes/2010/0315/opinions-health-cancer-larry-norton-ideas-opinions.html
Robert Langreth, 03.15.10, 6:00 PM ET
Larry Norton sees some of the toughest cases as deputy physician-in-chief for breast cancer at Memorial Sloan-Kettering Cancer Center. He has access to the most advanced imaging machines, the best surgeons and numerous new tumor-fighting drugs. But often the fancy technology helps only temporarily. Sometimes a big tumor will shrink dramatically during chemotherapy. Then all of a sudden it comes back in seven or eight locations simultaneously.
Norton thinks adding more mathematics to the crude science of cancer therapy will help. He says that oncologists need to spend much more time devising and analyzing equations that describe how fast tumors grow, how quickly cancer cells develop resistance to therapy and how often they spread to other organs. By taking such a quantitative approach, researchers may be able to create drug combinations that are far more effective than the ones now in use. "I have a suspicion that we are using almost all the cancer drugs in the wrong way," he says. "For all I know, we may be able to cure cancer with existing agents."
His strategy is unusual among cancer researchers, who have tended to focus on identifying cancer-causing genes rather than writing differential equations to describe the rate of tumor spread. Yet adding a dose of numbers has already led to important changes in breast cancer treatment. The math of tumor growth led to the discovery that just changing the frequency of chemo treatments can boost their effect significantly.
In the future Norton's theorizing may lead to new classes of drugs. Researchers have always assumed tumors grow from the inside out. His latest theory, developed in collaboration with Sloan-Kettering biologist Joan Massagué, asserts that tumors grow more like big clusters of weeds. They are constantly shedding cells into the circulatory system. Some of the cells form new tumors in distant places. But other wayward cells come back to reseed the original tumor, making it grow faster. It's like hardened terrorists returning to their home villages after being radicalized abroad and recruiting even more terrorists, says Massagué, who in December showed that the self-seeding process happens in laboratory mice. If this model works in humans, it will open up new avenues for treatment. It suggests that to cure cancer, doctors need to come up with drugs that stop the seeding process. These drugs may be different from the current crop of drugs, which are designed to kill fast-dividing cells.
Among other mysteries, self-seeding may explain why tumors sometimes regrow in the same location after being surgically removed: not necessarily because surgeons failed to remove part of the original tumor but because some itinerant cancer cells returned later to their original home to start a new tumor in the same place.
Norton, 62, got a degree in psychology from the University of Rochester, then an M.D. from Columbia University. For a while during college he thought he would make a career as a saxophonist and percussionist. The remnant of that dream is a vibraphone in his office in Memorial's new 16-story breast cancer center.
Ever since he was a fellow at the National Cancer Institute in the 1970s he has been trying to come up with mathematical laws that describe tumor growth. He treated a lymphoma patient whose tumor shrank rapidly during chemotherapy. A year later the cancer returned worse than ever. The speed with which the tumor grew back didn't jibe with the prevailing notion that most tumors grew in a simple exponential fashion.
Working with NCI statistician Richard Simon, Norton came up with a new model of tumor growth based on the work of the 19th-century mathematician Benjamin Gompertz. The concept (which other researchers proposed in the 1960s) holds that tumor growth generally follows an S-shape curve. Microscopic tumors below a certain threshold barely grow at all. Small tumors grow exponentially, but the rate of growth slows dramatically as tumors get bigger, until it reaches a plateau. A corollary of this: The faster you shrink a tumor with chemo, the quicker it will grow back if you haven't killed it all.
Based on these rates of growth, Norton argued that giving the same total dose of chemotherapy over a shorter period of time would boost the cure rate by limiting the time tumors could regrow between treatments. The concept got a skeptical reaction initially. "People said it was a total waste of time," he recalls. It took decades before Norton was able to prove his theory. But in 2002 a giant government trial showed that giving chemotherapy every two weeks instead of every three lowered the risk of breast cancer recurrence by 26% over three years, even though the two groups got the same cumulative dose.
Today Norton's "dose-dense" regimen is common practice for certain breast cancer patients at high risk of relapse after surgery. Timing adjustments are also showing promise in other tumor types. Last October a Japanese trial found that ovarian cancer patients lived longer if they received smaller doses of chemotherapy weekly rather than getting larger doses every three weeks, according to results published in The Lancet.
"Larry has been one of the real thinkers in this area," says Yale University professor and former NCI head Vincent DeVita. But designing better treatment schedules doesn't get as much credit as the glamorous business of inventing drugs.
Norton's latest theory about how tumors grow is derived from Massagué's pioneering research. It is consistent with Gompertz's growth curves and ties together two essential features of cancer that researchers had long considered separate--cell growth and metastasis.
Their collaboration started five years ago, when Massagué called Norton and shared a startling finding that was emerging from his laboratory. Massagué was studying how tumors spread from an organ such as the breast to the lungs, brain and other faraway places. He took human breast tumor cells, implanted them in mice and waited for metastases to occur. He analyzed cells that had metastasized to see what genes were overactive. None of the genes implicated in the spread of cancer to distant organs had to do with excessive cell division, it turned out. Instead, they all related to the ability to infiltrate and adapt to new environments.
The finding seemed to contradict doctors' impression that the fastest-growing tumors are also the most likely to spread. Pondering how to reconcile the two ideas, Norton and Massagué theorized that tumor cells released into the bloodstream sometimes are attracted back to the original tumor and help it expand.
Self-seeding may explain why large tumors tend to grow (in percentage terms) more slowly than small tumors: It could be that growth is a function of surface area rather than volume. Tumors that are efficient seeders may kill people by promoting the seeding process, not because they have a higher exponential growth rate.
It took Massagué four years of work to prove that self-seeding occurs in laboratory mice. Now comes the tricky part: coming up with drugs that block tumor seeding. Massagué and Norton have identified four genes involved in seeding and are testing for drugs to block them. Convincing drug companies to go along could be difficult; it's easier to see whether a drug shrinks tumors than to see whether it stops evil cells from spreading. But Norton believes that doing this hard work may be the key to a cure.
The price I've heard is 3.5B (Eu not $).
It's not cheap but Germany is the 2nd largest generic market in the world. TEVA is up nearly 2% here now on the news.
And the winner is - Teva.
Wonder if Bydureon (LAR) will have Victoza's black box warning for thyroid c-cell tumors as well.
Abraxis' Abraxane meets lung cancer study goal
http://finance.yahoo.com/news/Abraxis-Abraxane-meets-lung-apf-1676130649.html?x=0&.v=1
LOS ANGELES (AP) -- Abraxis BioScience Inc. said Wednesday its drug Abraxane met key treatment goals in a late-stage lung cancer study.
The company said Abraxane with Taxol, in combination with chemotherapy, improved the overall response rate of patients in the 1,052 patient study. The study focused on patients receiving initial treatment for lung cancer and compared the Abraxane combination with patients only receiving Taxol and another chemotherapy, carboplatin.
Abraxane is already approved as a breast cancer treatment. The company expects to ask for FDA approval as a lung cancer treatment in 2011.
Shares of Abraxis jumped $12.77, or 32.1 percent, to $52.62 in morning trading. The stock has traded between $24.52 and $57.60 over the last 52 weeks.
Protalix Initiates a Phase I Clinical Trial of Acetylcholinesterase for Biodefense Indications
http://finance.yahoo.com/news/Protalix-Initiates-a-Phase-I-prnews-2521507457.html?x=0&.v=1
Press Release Source: Protalix BioTherapeutics, Inc. On Wednesday March 17, 2010, 7:00 am EDT
CARMIEL, Israel, March 17 /PRNewswire-FirstCall/ -- Protalix BioTherapeutics, Inc. (NYSE-Amex: PLX) announced today that it has initiated a phase I clinical trial of PRX-105, the Company's plant cell expressed pegylated recombinant human acetylcholinesterase product candidate in development for biodefense indications. The trial is designed to study the safety of PRX-105 by administering a bolus intravenous injection of PRX-105 in healthy volunteers. The U.S. Food and Drug Administration (FDA) and the Israeli Ministry of Health have each accepted the Company's exploratory Investigational New Drug application to commence the phase I clinical trial of PRX-105. Pre-clinical studies have previously indicated that PRX-105 successfully protects animals exposed to organophosphate nerve gas agent analogs, in both the prophylactic and post-exposure settings. In addition, the safety of PRX-105 has been demonstrated in a well-controlled study in rodents performed under good laboratory practices.
Before applying for marketing approval from the FDA and comparable foreign regulatory authorities, the Company will be required to perform additional safety studies in healthy volunteers, as well as additional studies in animals. Efficacy trials of PRX-105 in humans (phase II and phase III) are not required given the nature of the indication for which PRX-105 is being developed.
Nerve gas agents, such as organophosphates, bind to, and inhibit, the action of acetylcholinesterase, an endogenous enzyme that breaks down the neurotransmitter, acetylcholine, in humans. The loss of the acetylcholinesterase function results in an accumulation of toxic levels of acetylcholine, which has deleterious effects on major organ systems, including the heart, lung and central nervous system. PRX-105 acts as a bioscavenger of the organophosphates that affect the acetylcholinesterase, thereby causing a re-balancing of acetylcholine levels.
"We are excited that a second product candidate produced through our ProCellEx™ protein expression system has advanced to the clinical stage," said Dr. David Aviezer, President and Chief Executive Officer of Protalix. "The treatment options currently available to victims of nerve gas attacks are limited and current rescue therapies have significant, life threatening side effects which give rise to the urgent need for an alternative biological solution, as recently indicated by U.S. government agencies."
The PRX-105 program is being conducted in collaboration with Professor Hermona Soreq, from the Hebrew University in Jerusalem, Israel, a world leader in the field of acetylcholinesterase research, and based on patents that were licensed to Protalix Ltd. by Yissum, the Technology Transfer Company of the Hebrew University. "The acetylcholinesterase project is important project to me, both as an inventor and as a scientist, as Protalix is developing the acetylcholinesterase in its facility in Carmiel, Israel, and the protein appears to be available for use for multiple clinical needs, especially in the neurological degenerative disease area," said Professor Soreq.
The Company is in discussions with both civil and military agencies in the United States and Israel with respect to this project.
About Protalix
Shire Gets INTUNIV Paragraph IV Notice Letter From Teva
http://www.shire.com/shireplc/en/investors/investorsnews/irshirenews?id=351
Shire PLC (SHP.LN) said Tuesday it has received a Paragraph IV Notice Letter from Teva Pharmaceuticals U.S.A, Inc. advising of the filing of an Abbreviated New Drug Application, or ANDA, for a generic version of Shire's 1 mg, 2 mg, 3 mg, and 4 mg guanfacine hydrochloride extended release tablets, INTUNIV.
MAIN FACTS:
-INTUNIV is protected by three FDA Orange Book listed patents: U.S. Patent No. 5,854,290, Use of Guanfacine in the Treatment of Behavioral Disorders; U.S. Patent No. 6,287,599 and U.S. Patent No. 6,811,794 both titled Sustained Release Pharmaceutical Dosage Forms with Minimized pH Dependent Dissolution Profiles.
-The three patents expire in 2015, 2020 and 2022, respectfully.
-Shire is currently reviewing the details of Teva's Paragraph IV Notice Letter which was only directed to the `599 and `794 patents.
-Hatch-Waxman exclusivity period for INTUNIV runs until September 2, 2012 therefore, ANDAs for generic versions of INTUNIV cannot be approved prior to the end of that exclusivity period.
-Under the Hatch-Waxman Act, Shire has 45 days from the receipt of the Notice Letter to determine if it will file a patent infringement suit.
-If Shire brings suit pursuant to the Hatch Waxman regulations, a stay of approval of up to 30-months will be imposed by the FDA on Teva's ANDA.
Btw, Zvi Karchi, father of the Hagai Evogene's co-founder, is the geneticist behind the famous Israeli melons.
EASL
abstracts for posters presentations at EASL are available for viewing:
http://www.kenes.com/easl2010/posters/
SAFETY AND ANTIVIRAL ACTIVITY OF THE HCV NON-NUCLEOSIDE POLYMERASE INHIBITOR VX-222 IN TREATMENT-NAïVE GENOTYPE 1 HCV-INFECTED PATIENTS
http://www.kenes.com/easl2010/Orals/137.htm
M. Rodriguez-Torres1, E. Lawitz2, B. Conway3, K. Kaita4, A.M. Sheikh5, R. Ghalib6, R. Adrover7, C. Cooper8, M. Silva7, M. Rosario9, B. Bourgault10, L. Proulx10, J.G. McHutchison11
1Fundacion de Investigacion de Diego, Santurce, PR, 2Alamo Medical Research, San Antonio, TX, USA, 3University of British Columbia, Vancouver, BC, 4University of Manitoba, Winnipeg, MB, Canada, 5GI Specialists of Georgia, Marietta, GA, 6The Liver Institute at Methodist Dallas, Dallas, TX, USA, 7ACLIRES, Buenos Aires, Argentina, 8University of Ottawa, Ottawa, ON, Canada, 9Hospital Universitario Austral, Buenos Aires, Argentina, 10Vertex Pharmaceuticals Incorporated, Cambridge, MA, USA, 11ViroChem Pharma Inc., Laval, QC, Canada, 12Duke University Medical Center, Durham, NC, USA. *rodztorres@coqui.net
Background and aims: VX-222 is a novel non-nucleoside hepatitis C virus (HCV) polymerase inhibitor with potent in vitro activity. Safety, tolerability, pharmacokinetics and antiviral activity of VX-222 were assessed in a phase Ib/IIa multicenter, randomized, double-blinded, placebo-controlled, dose-ascending study in HCV-infected patients.
Methods: Treatment-naïve HCV genotype 1 patients were randomized to receive VX-222 at doses of 250 mg BID, 500 mg BID, 750 mg BID, 1500 mg QD or placebo for 3 days in a treatment:placebo ratio of 6:2 (8 patients/cohort). Peginterferon-alfa-2a (P) plus ribavirin (R) was offered to patients at end of study (day 4) for up to 48 weeks, as judged appropriate by the investigator. PR treatment was discontinued in patients who had not experienced a =2 log10 HCV RNA level decline at week 12. VX-222 plasma levels were assessed at multiple time points over 12 hours, on days 1 and 3.
Results: Twenty-four patients were enrolled in the first three cohorts. VX-222 exposure increased in a dose-related manner. On day 3, the mean AUC0-12h and Cmax values were 19,490 ng*h/mL (CV 41%) and 2,959 ng/mL (CV 29%), 29,848 ng*h/mL (CV 54%) and 5,044 ng/mL (CV 36%), and 62,952 ng*h/mL (CV 112 %) and 10,288 ng/mL (CV 112%) for the 250 mg, 500 mg, and 750 mg BID groups, respectively. The mean HCV RNA decline achieved on day 4 with placebo, 250 mg, 500 mg, and 750 mg VX-222 BID was 0.1 log10 (range: 0.3 increase to 0.5 decline), 3.1 log10 (range: 2.0 to 4.2), 3.4 log10 (range: 3.2 to 3.6), and 3.2 log10 (range: 2.3 to 3.8), respectively. All AEs reported were mild to moderate, and the most frequently reported AEs by patients that received either active drug or placebo were diarrhea (25%), headache (20%) and nausea (12%). No clinically relevant laboratory abnormalities were reported.
Conclusions: VX-222 was well tolerated and a mean HCV RNA decline of >3 log10 at day 4 was observed in each cohort, results of the fourth cohort evaluating QD dosing will also be presented. These results support further evaluation of VX-222 in combination with peginterferon and ribavirin in the treatment of HCV.
SILEN-C2: EARLY ANTIVIRAL ACTIVITY AND SAFETY OF BI 201335 COMBINED WITH PEGINTERFERON ALFA-2A AND RIBAVIRIN (PEGIFN/RBV) IN CHRONIC HCV GENOTYPE-1 PATIENTS WITH NON-RESPONSE TO PEGIFN/RBV
http://www.kenes.com/easl2010/Orals/298.htm
M. Sulkowski1, M. Bourliere2, J.-P. Bronowicki3, A. Streinu-Cercel4, L. Preotescu4, T. Asselah5, J.-M. Pawlotsky6, S. Shafran7, S. Pol8, F.A. Caruntu4, S. Mauss9, D. Larrey10, C. Häfner11, Y. Datsenko11, J. Stern12, R. Kubiak11, G. Steinmann11
1Department of Viral Hepatitis, Johns Hopkins University, Baltimore, MD, USA, 2Hôpital Saint Joseph, Marseille, 3Hôpital de Brabois, Vandoeuvre Cedex, France, 4'Prof. Dr. Matei Bals' Institute of Infectious Diseases 1, Bucharest, Romania, 5Hôpital Beaujon, Clichy Cedex, 6Hôpital Henri Mondor, Créteil, France, 7University of Alberta, Edmonton, AB, Canada, 8Hôpital Cochin, Paris, France, 9Center for HIV and Hepatogastroenterology, Düsseldorf, Germany, 10Hôpital Saint-Eloi, Montpellier Cedex, France, 11Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach/ Riß, Germany, 12Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, USA. *msulkowski@jhmi.edu
Background and aims: BI 201335 is a potent HCV NS3/4A protease inhibitor being studied in phase IIb trials of chronic HCV genotype-1 (GT1) infection.
Methods: In a double-blind, randomized, parallel group design, HCV GT1 patients with confirmed non-response to at least 12 wks of PegIFN/RBV treatment were randomized 1:2:1 to (1) 240 mg BI 201335 once daily (QD), (2) 240 mg BI 201335 QD after a 3 day lead-in phase (LI) of PegIFN/RBV, and (3) 240 mg BI 201335 twice daily (BID) after a 3 day LI. Relapsers and patients with liver cirrhosis were excluded. In each group, treatment is for 24 wks with a background of PegIFN (180 µg/wk) and RBV (1000/1200mg/d). Pre-specified Interim analysis after 12 weeks of therapy is reported. Viral rebound is defined as an increase in plasma HCV RNA = 1 log10 on-treatment from nadir or confirmed increase = 100 IU/ml if previously undetectable.
Results: 288 patients were treated (mean age 49 +/- 9 years; mean BMI 26.4 +/- 4.4 kg/m2; mean log10 HCV RNA at baseline 6.6 IU/mL). BI 201335 with PegIFN/RBV was overall well tolerated and demonstrated potent antiviral activity in all dose groups (Table). Mean ALT improved in all groups. 8% of patients prematurely discontinued treatment due to adverse events (AE). Most frequent AE were gastrointestinal disorders, mostly mild jaundice resulting from isolated unconjugated hyperbilirubinemia, (9.2%, 14.1% and 34.3% in groups 1, 2 and 3) and mostly mild to moderate rash or photosensitivity reactions (severe rash in 1.3, 0.7 and 5.7% in groups 1, 2 and 3).
ONCE-DAILY NS5A INHIBITOR (BMS-790052) PLUS PEGINTERFERON-ALPHA-2A AND RIBAVIRIN PRODUCES HIGH RATES OF EXTENDED RAPID VIROLOGIC RESPONSE IN TREATMENT-NAIVE HCV-GENOTYPE 1 SUBJECTS: PHASE 2A TRIAL
http://www.kenes.com/easl2010/Orals/297.htm
S. Pol1, G. Everson2, R. Ghalib3, V. Rustgi4, C. Martorell5, H.A. Tatum6, J. Lim7, C. Hezode8, U. Diva9, P.D. Yin9, R. Hindes9
1Hôpital Cochin, Paris, France, 2University of Colorado Denver & Hospital, Denver, CO, 3The Liver Institute at Methodist Dallas Medical Center, Dallas, TX, 4Metropolitan Research, Fairfax, VA, 5The Research Institute, Springfield, MA, 6Options Health Research, Tulsa, OK, 7Yale University School of Medicine, New Haven, CT, USA, 8CHU Henri Mondor, Creteil, France, 9Bristol-Myers Squibb Company, Wallingford, CT, USA. *stanislas.pol@cch.aphp.fr
Background: BMS-790052 is a first-in-class, highly potent, once-daily HCV NS5A inhibitor. In Phase I studies in HCV-infected subjects, BMS-790052 was well-tolerated and exhibited potent antiviral activity.
Methods: In this double-blind study, 48 subjects were randomized 1:1:1:1 to receive placebo, 3 mg, 10 mg or 60 mg of BMS-790052, once-daily in combination with peginterferon-alpha-2a and ribavirin (P/R) for 48 weeks in treatment-naive HCV genotype 1-infected subjects. The primary endpoint was the proportion of subjects with extended rapid virologic response (eRVR) defined as HCV RNA < 10 IU/mL at both Weeks 4 and 12.
Results: Subject baseline and demographic characteristics were well-balanced across treatment arms (n = 12/arm), with mean baseline HCV RNA 6.5 log10 IU/mL. The proportion of subjects achieving eRVR was 42%, 83% and 75% in the 3 mg, 10 mg and 60 mg BMS-790052 + P/R arms, respectively, compared to 8% for P/R. Safety was comparable across treatment arms (see table). Adverse events were consistent with those commonly observed with P/R. Confirmed viral breakthrough was not observed in the 10 mg and 60 mg BMS-790052 arms through Week 12.
Conclusions: BMS-790052 is a potent once-daily NS5A inhibitor that yielded higher eRVR, RVR, and cEVR rates when combined with P/R than P/R alone. The addition of BMS-790052 to P/R was well-tolerated with an AE profile comparable to P/R. These results support further development of BMS-790052 in combination with P/R or other HCV antivirals.
Too much zigzagging (between India and Ex-India data, 25 IU/cc lyophilized formulation and 100 IU/cc liquid formulation, pH4 and pH7) in this story to make me stay away. Great summary and notes here:
http://siliconinvestor.advfn.com/subject.aspx?subjectid=57918
If I were a patient, I'd try MitraClip first assuming I can get the surgical procedure later.
From wiki - Jain KK. Textbook of Personalized Medicine, Springer, 2009.
...Moreover "theranostic" is confusing and not understood by most people and should be deleted from the vocabulary. There is no difficulty in describing this concept without using a special term. Diagnostics used to guide therapeutics are also called “companion diagnostics”. If one has to use a single word to describe a test linked to therapy, one can use "pharmacodiagnostic", which is more appropriate and easy to understand.
I am aware that some cannot take statin, but this drug will have to go a long way to convince me it improves cardiovascular parameters. Just lowering cholesterol is not enough.
Peter M. Nilsson, M.D., Ph.D. in the accompanying editorial on results from pre-specified group of patients with dyslipidemia:
BIOD: VIAject
Do you know if a disposable insulin pen formulation was included in the NDA?
Stage IV melanoma patients have very few options and awful 5-year survival rates. Pazdur is quite right calling DTIC (and I'd add Temodar) "toxic placebo". IL-2 has better effect on the disease but AEs are too severe for most patients to tolerate. Ipilimumab's MoA is not as smart as Provange, it isn't specific, rather it is generally upregulating the immune response therefore causing many AEs. However, like you said the bar in melanoma isn't all that high and ipi's risk/benefit profile makes me believe it will be approved. Question is will the FDA want to see the ipi+DTIC in 1st line data also or will the ipi+MDX-1379 in 2nd line data will be enough.
The Puzzling Rise and Fall of a Dark-Horse Alzheimer's Drug
http://www.sciencemag.org/cgi/content/summary/327/5971/1309
By Greg Miller
The announcement last week that a closely watched phase III clinical trial for Alzheimer’s disease had failed to show a significant effect deals yet another demoralizing blow to patients, families, and caregivers. It may also mark the beginning of the end to one of the most unusual stories in Alzheimer’s drug development.
The trial involved a drug called Dimebon, which catapulted into the limelight with a spectacularly successful trial published in The Lancet in 2008. “It looked better than anything we’d ever seen before,” says Samuel Gandy, an Alzheimer’s researcher at Mount Sinai School of Medicine in New York City.
Dimebon was an unlikely Alzheimer’s drug. An antihistamine introduced in Russia in 1983, it turned up in a screen for potential Alzheimer’s drugs led by scientists at the Institute of Physiologically Active Compounds in Chernogolovka, Russia. In followup experiments, the drug improved the performance of memory-impaired rats, and a pilot study with 14 Russian Alzheimer’s patients showed encouraging results, published in a 2001 paper in the Annals of the New York Academy of Sciences.
Based on those findings, one of the Russian scientists, Sergey Bachurin, came to the United States to seek investors and partners in developing the drug. Bachurin persuaded San Francisco–based biotech entrepreneur David Hung to establish a company, called Medivation, and reportedly exchanged the rights to the drug for equity in the company. With initial support from private investors, Medivation recruited several top experts to design a larger clinical trial. The experts included Paul Aisen, a neurologist at the University of California, San Diego, who oversees government-sponsored clinical trials as director of the Alzheimer’s Disease Cooperative Study; Rachelle Doody of Baylor College of Medicine in Houston, Texas; and Mary Sano of Mount Sinai.
The results were remarkable: The 2008 Lancet study, a double-blind, placebo-controlled trial, reported that 89 people with mild to moderate Alzheimer’s disease who took Dimebon showed significant improvements in memory and cognition, as well as the ability to carry out the activities of daily life. The effects far surpassed those of any Alzheimer’s drug on the market or in development, and Hung says several pharmaceutical companies bid to purchase the rights to Dimebon. Pfizer won, paying $225 million.
The Lancet findings struck many researchers as too good to be true, says Rudolph Tanzi, an Alzheimer’s researcher at Harvard University. “Nobody could figure out what an antihistamine does” to fight Alzheimer’s disease, says Sam Sisodia of the University of Chicago in Illinois. Several ideas have been floated, Sisodia says, but supporting evidence is scant. Still, he and others say they were willing to suspend their disbelief, largely because of the involvement of Aisen, Doody, and Sano. “If you had to pick the five best trialists in the world, they would be three of them,” Gandy says.
But the new trial, despite a design almost identical to that of the Lancet study, yielded dramatically different results. It enrolled 598 patients with mild to moderate Alzheimer’s. This time, however, there were no significant differences between the Dimebon and placebo groups. “It’s hugely disappointing,” says Aisen. He says he’s at a loss to explain the discrepancy, although he notes that it’s not unheard of for a drug to have both positive and negative trials before winning approval. Gandy, however, says, “I’m not sure that there has ever been such a night-and-day difference in replicate trials that turned out to be biological variation.” Medivation and Pfizer are poring over the data in search of an explanation, says Hung, who declined to discuss their leading hypotheses. For now, the companies will continue with three other Dimebon trials already under way for Alzheimer’s disease, in addition to one for Huntington’s disease.
But to some, Dimebon is starting to look like a dark horse whose race is run. “I don’t think that the drug is dead and buried today, but we need to get some clarity or good news soon,” Gandy says.
There's nothing we didn't know in the knol piece. If you wanna know when the author first wrote the stuff, look at 'versions'. The one on ipi was written 3 days ago and he edited several times since.
Knol is a Google project:
http://en.wikipedia.org/wiki/Knol
The date should be listed on the right. The one posted by North was edited: 13 hours ago. This one from the same author was last edited one day ago.
http://knol.google.com/k/krishan-maggon/monoclonal-antibody-market-2009/3fy5eowy8suq3/86#
Sequencing technology cost declines in price and improves in
throughput, accuracy, and time. Still accuracy isn't good enough and challenges remain regarding data (storage, mining, and most importantly - analysis). Without a whole genome reader software it is all useless and perhaps even dangerous.
[OT] Dr. Hood
Never had the honor to work with him. I follow his work for several years now and am amazed:
He is the founder of Systems Biology. His studies led to the development of DNA sequencers. He is the founder of the Systems Biology Institute, a non-profit research institute that attracted the best in the field and publishes more per capita than any other genomic institute in the States. At at his advanced age he is not quiting. If even some of his dreams come true, then medicine will be transformed.
Scientific Meeting Calendar
NOTE: ANYONE MAY UPDATE THIS FILE
Edits: Removed old entries; Added: ESMO, IOF, ARVO, HRS,
MARCH 2010
American Academy of Orthopedic Surgeons - AAOS
New Orleans, LA
March 9-13, 2010
http://www.aaos.org/
Society of Interventional Radiology - SIR
Tampa, Fl
March 13-18, 2010
http://www.sirweb.org/
American College of Cardiology - ACC
Atlanta, GA
March 14-16, 2010
http://acc.org/
Society of Gynecological Oncologists - SGO
San Francisco, CA
March 14-17, 2010
http://www.sgo.org/
American Society for Clinical Pharmacology & Therapeutics - ASCPT
Atlanta, GA
March 17-20, 2010
http://ascpt.org/
International Conference Primary Therapy of Early Breast Cancer - SG-CAP
St Gallen, Switzerland
March 18-20, 2010
http://www.oncoconferences.ch/
American College of Medical Genetics - ACMG
Albuquerque, New Mexico
March 24-28, 2010
http://www.acmgmeeting.net/
APRIL 2010
European Congress on Clinical Microbiology and Infectious Diseases
- ASCMID
Vienna, Austria
April 10-13, 2010
http://www.escmid.org/
American Academy of Neurology - AAN
Toronto, Canada
April 10–17
http://www.aan.com/
National Kidney Foundation - NKF
Orlando, FL
April 13-17, 2010
http://www.kidney.org/news/meetings.cfm
European Association for the Study of the Liver - EASL
Vienna, Austria
April 14-18, 2010
http://www.easl.eu/
American Association for Cancer Research - AACR
Washington, D.C.
April 17-21, 2010
http://www.aacr.org/
World Vaccine Congress - WVCDC
Washington, D.C.
April 19-22, 2010
http://www.terrapinn.com/2010/wvcdc/index.stm
International Society for Heart and Lung Transplantation - ISHLT
Chicago, IL
April 21-24, 2010
http://www.ishlt.org/meetings/annualMeeting.asp
American Association of Clinical Endocrinologists - AACE
Boston, MA
April 21–25, 2010
http://www.aace.com/meetings/ams/2010/
International Conference on Antiviral Research - ICAR
San Francisco, CA
April 25-28, 2010
http://isar.phrm.cf.ac.uk/
European Lung Cancer Conference - ESMO
Geneva, Switzerland
April 28 - May 1, 2010
http://www.esmo.org/events/lung-2010-iaslc.html
MAY 2010
American Association of Neurological Surgeons - AANS
Philadelphia, PA
May 1-5, 2010
http://www.aans.org/
Digestive Disease Week - DDW
New Orleans, LA
May 1-5, 2010
http://www.ddw.org/
Society of Thoracic Surgeons - AATS
Toronto, ON, Canada
May 1 - 5, 2010
http://www.aats.org/annualmeeting/
World Congress on Osteoporosis - IOF
Florence, Italy
May 5-8, 2010
http://www.iofwco-ecceo10.org/
Association for Research In Vision and Ophthalmology - ARVO
Fort Lauderdale, Fl
May 2 – 6, 2010
http://www.arvo.org/EWEB/startpage.aspx?site=am2010
The Heart Rhythm Society - HRS
Denver, CO
May 12-15, 2010
http://www.hrsonline.org/Sessions/
American Thoracic Society - ATS
New Orleans, LA
May 14-19, 2010
http://conference.thoracic.org/
JUNE 2010
European Society of Human Genetics - ESHG
Gothenburg, Sweden
June 12-15, 2010
https://www.eshg.org/
OCTOBER 2010
American Association for the Study of Liver Diseases - AASLD
Boston, Massachusetts
October 29 - November 2, 2010
http://www.aasld.org/
NOVEMBER 2010
American Society of Human Genetics - ASHG
Washington, DC
November 2-6, 2010
http://www.ashg.org/
----
Procedure for Updating Calendar
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