Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
ARNA - Thought the results would come out later this month. If the results are good $5 Sep call writers are going to get killed. They were selling for 20 cents today.
RIGL - AF had an interesting piece and I think some of his points are valid.
"Rigel Pharmaceuticals is selling more stock, but wasn't the small drug maker supposed to raise money by partnering its experimental rheumatoid arthritis drug?
Announced Wednesday after the close, Rigel said it intends to sell 6 million shares with an over-allotment option for another 900,000-shares. At Wednesday's closing price, the offering would gross just under $53 million.
Rigel ended the second quarter with about $80 million in cash, enough to get the company into the middle of next year.
The new offering will bolster the company's bank account and could help it at the negotiating table as it seeks a partner for R788, a novel pill for rheumatoid arthritis.
Or, does this new offering signal that Rigel is having trouble finding a partner interested in R788?
The drug is certainly not without controversy. An oral pill for rheumatoid arthritis could be a very big deal given that current medicines -- most notably the so-called "anti-TNFs" like Amgen's(AMGN Quote) Enbrel and Abbott Labs' Humira -- are given by injection.
But in July, Rigel reported negative results from a phase II study in which R788 failed to improve the rheumatoid arthritis of patients who had previously failed anti-TNF medicines. The setback sent Rigel shares sharply lower and raised questions about the future of the drug. Two previous phase II studies of R788 in patients who had not yet been treated with anti-TNFs yielded more positive results.
Rigel downplayed the negative results from this most recent phase II study, insisting that the primary goal was to develop R788 first as drug that would compete head to head against the anti-TNFs like Enbrel and Humira. This is where the drug has shown more promise in phase II studies.
The challenge of that approach is that Enbrel and Humira are very effective drugs with well-known safety records, and a potential partner may not feel comfortable funding trials that try to directly unseat these very well established therapies. Moreover, R788 still has unresolved safety questions, including an elevated high blood pressure risk."
http://www.thestreet.com/story/10599708/2/psst-these-drug-firms-are-getting-bought-biobuzz.html
SPPI - Blade, any thoughts as to the sell off after the label was made public? Was there an expectation for a better label or was this the best they could have gotten?
vvus side effects - According to the presentation SAE's were minimal and as expected. Dropout rate for the high dose from what I recall was 18% vs about 7 % for placebo. It looks like they will target this drug for the seriously obese who need to lose a lot of pounds or they'll die anyway.
VVUS patent - Good point. If the combo works then maybe an enterprising generic drug company could work on a pill with a similar controlled release aspect of Qnexa.
Qnexa - Thats a valid question and the only reason I can think of is that Qnexa uses the perfect combination of both generics and probably has a patent for the combination. Could be a problem down the road given the rigid obviousness guidelines patents are assessed with these days.
vvus - I believe safety was a huge concern and the share price was suppressed because of that. I'm not too familiar with the drug but I believe it contains two ingredients which individually cause serious side effects. It appears that the concerns have been removed (for now) and the drug is now a potential block buster.
qnexa - Probably depends on ARNA data and also on full Qnexa safety data. If lorcaserin bombs and Qnexa is relatively safe I think its probably going to be a blockbuster drug.
OSIR - Osiris Therapeutics Announces Preliminary Results for Prochymal Phase III GvHD Trials
Source: Osiris Therapeutics, Inc.
On Tuesday September 8, 2009, 8:01 am EDT
COLUMBIA, Md.--(BUSINESS WIRE)--Osiris Therapeutics, Inc. (NASDAQ: OSIR - News) today announced preliminary results for two phase III trials evaluating Prochymal for the treatment of acute graft versus host disease (GvHD). GvHD, the most common complication of bone marrow transplantation, is a life-threatening disease for which there is currently no approved treatment. Prochymal showed significant improvements in response rates in difficult-to-treat liver and gastrointestinal GvHD, however neither trial reached its primary endpoint.
Key findings from the GvHD trials include:
There was no statistical difference between Prochymal and placebo on the primary endpoints for either the steroid-refractory (35% vs. 30%, n=260) or the first-line (45% vs. 46%, n=192) GvHD trials.
The primary endpoint for the steroid-refractory GvHD trial (durable complete response) for the per-protocol population approached statistical significance (40% vs. 28%, p=0.087, n=179).
In patients with steroid-refractory liver GvHD, treatment with Prochymal significantly improved response (76% vs. 47%, p=0.026, n=61) and durable complete response (29% vs. 5%, p=0.046).
Prochymal significantly improved response rates in patients with steroid-refractory gastrointestinal GvHD (88% vs. 64%, p=0.018, n=71).
In pediatric patients, Prochymal showed a strong trend of improvement in response rates (86% vs. 57%, p=0.094, n=28).
“These data are still preliminary and further analysis is needed to gain a full appreciation of the results of these rigorous, double-blind, placebo-controlled trials,” said C. Randal Mills, Ph.D., President and Chief Executive Officer of Osiris Therapeutics. “We are encouraged to see Prochymal significantly improve response rates above standard of care in GvHD patients who currently have no good treatment options. We will meet with the FDA as soon as possible to discuss the most appropriate and efficient path forward for Prochymal in this life-threatening indication.”
Protocol 265 was designed to evaluate Prochymal as a first-line agent for the treatment of acute GvHD in combination with steroid therapy. The majority of patients in this trial were suffering from skin GvHD, which responded significantly better to steroids than had been previously reported in controlled trials. This high response rate to standard of care diminished the potential for Prochymal to demonstrate an effect.
In the more severe, steroid-refractory GvHD setting (protocol 280), the benefit of adding Prochymal to second-line therapy was evaluated. Prochymal approached statistical significance for the primary endpoint in the per-protocol patient population which is the group of patients that met all of the study protocol requirements, such as inclusion and exclusion criteria. Additionally, Prochymal significantly improved response rates to liver and gastrointestinal GvHD, for which there is currently no known reliable therapy. Notably, the Prochymal cohort had more severe GvHD (27% of Prochymal patients had grade D GvHD, the most severe form, vs. 16% of placebo patients, p=0.05).
Based upon the results of the steroid-refractory GvHD trial, Osiris plans to file an amendment with the FDA to the current expanded access program, broadening the entry criteria to include patients with severe GvHD of the liver.
Webcast and Conference Call
The Company has scheduled a webcast and conference call to discuss the GvHD clinical program today, September 8, 2009, at 9:00 AM ET. To access the webcast, visit the Investor Relations section of the company’s website at http://investor.osiris.com/events.cfm. Alternatively, callers may participate in the conference call by dialing (888) 352-6798 (U.S. participants) or (719) 325-2376 (international participants).
A replay of the conference call will be available approximately two hours after the completion of the call through September 15, 2009. Callers can access the replay by dialing (888) 203-1112 (U.S. participants) or (719) 457-0820 (international participants). The audio replay passcode is 8379243. To access a replay of the webcast, visit the Investor Relations section of the company's website at http://investor.osiris.com/events.cfm.
http://finance.yahoo.com/news/Osiris-Therapeutics-Announces-bw-3300462331.html?x=0&.v=1
placebo response - In some trials there is a limit to the amount of improvement. As an example (a simple one) if a patient takes a sugar pill to relieve pain and thinks that the sugar pill worked, then what more can a real drug do beyond the psychological benefit of relieving pain?
In any trial where a sugar pill actually improves one's symptoms there has to be some psychological benefit IMO. How else could the symptoms disappear mysteriously by simply taking a sugar pill? The same psychological benefit would appear in the control arm too but in most cases probably causes the results to not be stat sig due to a limit in the amount of improvement that can be achieved.
RA - NITEC PHARMA REPORTS POSITIVE AND HIGHLY
SIGNIFICANT PHASE III RESULTS FROM CAPRA-2 STUDY OF
LODOTRATM IN RA
-- CAPRA-2-data will be used to file for US marketing approval --
Basel/Reinach, Switzerland, 2nd September 2009 – Nitec Pharma AG (“Nitec” or “Nitec
Pharma”), a Switzerland-based specialty pharma company focused on the development and
commercialization of medicines to treat chronic inflammation and pain-related diseases, today
announced positive results from the second pivotal phase III trial for its lead product,
Lodotra™.
The CAPRA-2 study (Circadian Administration of Prednisone in Rheumatoid Arthritis-2) was a
12-week, multicentre, double-blind phase III trial evaluating the safety and efficacy of
Lodotra™ for the treatment of rheumatoid arthritis (“RA”), a chronic, progressive and disabling
autoimmune disorder. In total 350 patients, all inadequate responders to DMARD therapy,
were randomised in one of two arms to receive either Lodotra™ (5mg once daily), or placebo
in addition to their existing therapy. The primary efficacy endpoint was the ACR-20 response
rate, which is defined as at least a 20% improvement in a number of disease-specific criteria.
The key secondary endpoint was the change in the duration of morning stiffness of the joints.
CAPRA-2-data will be used to file for US marketing approval with the FDA together with the
data already available from the CAPRA-1 pivotal phase III trial which has shown the
superiority of Lodotra™ over standard prednisone treatment.
Lodotra™-treated patients showed an ACR-20 response of 49% compared to 29% in the
placebo group. The difference was highly significant (p=0.0002; LOCF). The reduction of
morning stiffness was 44% in the Lodotra™ group (21 % in the placebo group). This
difference was also highly significant (p=0.0008). Lodotra™ was safe and well tolerated. The
number of adverse events was low and comparable in both groups.
Dr. Anders Härfstrand, CEO of Nitec commented: “We are delighted to report successful and
very positive outcomes of the CAPRA-2 study. These strongly underline the benefits of
Lodotra™ in the treatment of RA. The study confirms clearly that the innovative delivery
system of Lodotra™ is able to adapt the timing of glucocorticoid treatment to a patient´s
circadian rhythm in order to improve the efficacy and safety of prednisone. CAPRA-2 is the
first pivotal phase III study to demonstrate the ACR-20 response of a very low dose of
prednisone as a primary endpoint. Following the successful European launches of Lodotra™
and the positive feedback that we have received from RA specialists, we look forward to
completing the regulatory process in the US.”
LodotraTM, Nitec’s novel single-pulse delayed-release (“SPDR”) low-dose prednisone tablet,
was launched in Germany by Merck KGaA, which holds the exclusive distribution rights for
Germany and Austria. In April 2009 Mundipharma acquired the distribution rights to LodotraTM
in the rest of Europe and Nitec retains all commercialization rights for the US and rest of the
world.
http://www.nitecpharma.com/downloads/Nitec%20announces%20Capra%202%20results.pdf
sppi - Raj seemed to be pretty happy with the label. I don't see the label on the FDA site yet. I guess once the label becomes public that could be another trigger for the share price to move up. December appears to be an important month for Zevalin, with the ASH meeting and possible completion of enrollment on eoquin. I also wonder whether this approval could trigger more institutions to start buying.
sppi -
It could even sell off on approval, since the run-up has been quite remarkable
Biogen offers $14.50 a share for Facet Biotech
By Wallace Witkowski
2%1%0%-1%-2%
10a11a12p1p2p3p
BIIB FACT
SAN FRANCISCO (MarketWatch) -- Biogen Idec Inc. (BIIB 50.46, +0.55, +1.10%) said Friday it offered $14.50 a share for all outstanding shares of Facet Biotech Corp. (FACT 8.79, -0.03, -0.34%) . With about 23.9 million shares outstanding, the deal values the Redwood City, Calif.-based biotech at $346.6 million, or at a 64% premium to Facet's closing price of $8.82 a share on Thursday.
http://www.marketwatch.com/story/biogen-offers-1450-a-share-for-facet-biotech-2009-09-04?siteid=yhoof2
FDA Approves ZEVALIN(R) Expanded Label as Part of First-Line Therapy in Treatment of Follicular Non-Hodgkin's Lymphoma
Last update: 9/4/2009 10:46:00 AM
Label Expands Treatable Population To Approximately 43,000 Patients Annually
IRVINE, Calif., Sep 04, 2009 (BUSINESS WIRE) -- Spectrum Pharmaceuticals (NasdaqGM:SPPI), a commercial-stage biotechnology company with a focus in oncology, today announced ZEVALIN(R) (ibritumomab tiuxetan), a CD20-directed radiotherapeutic antibody, received approval from the U.S. Food and Drug Administration (FDA) for an expanded label for the treatment of patients with previously untreated follicular non-Hodgkin's Lymphoma (NHL), who achieve a partial or complete response to first-line chemotherapy. This new and expanded indication supplements the 2002 FDA approval of ZEVALIN as treatment for patients with relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma.
"We believe the approval of ZEVALIN as an effective treatment option following a first-line regimen represents a notable advance in the treatment of non-Hodgkin's Lymphoma, and significantly expands the addressable population for ZEVALIN," said Rajesh C. Shrotriya, MD, Chairman, Chief Executive Officer, and President of Spectrum Pharmaceuticals. "We are confident that the strategic and tactical initiatives we have implemented will overcome the clinical, logistical, and reimbursement challenges that have previously hindered physician and patient access to ZEVALIN."
The approval of the new indication was based on data from the FIT Study (First-line Indolent Therapy). The multicenter, randomized, open-label Phase 3 study evaluated the safety and efficacy of ZEVALIN in 414 patients with CD20-positive follicular NHL who had achieved a partial response or a complete response after receiving a first-line chemotherapy regimen. Patients were treated with one of the following first-line chemotherapy regimens: chlorambucil, fludarabine, fludarabine-containing regimen, CVP/COP, CHOP, CHOP-like, or rituximab-containing chemotherapy. At 3.5 years of follow-up, the FIT trial demonstrated that when used as part of first-line chemotherapy for patients with follicular NHL, ZEVALIN significantly improved the median progression-free survival time from 18 months (control arm) to 38 months (ZEVALIN arm) (p<0.0001).
ZEVALIN Control p-value (n=208) (n=206) Median PFS 38 months 18 months
Updated results with an additional year of follow up were presented at the American Society of Hematology 2008 Annual Meeting. The safety profile of ZEVALIN was consistent with previous clinical studies, with hematologic toxicity as the most common adverse reaction in the FIT study.
"Our institution is one of the leading cancer research centers in the United States investigating the clinical utility of ZEVALIN in NHL therapy," said Stephanie A. Gregory, MD, The Elodia Kehm Chair of Hematology, Professor of Medicine, and Director, Section of Hematology at Rush University Medical Center. "We believe that the approval of ZEVALIN as part of first-line chemotherapy represents an important advance in the treatment of patients with NHL."
The National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium currently lists chemotherapy followed by radioimmunotherapy, such as ZEVALIN, for patients with follicular NHL with a Category 1 recommendation. The Centers for Medicare & Medicaid Services (CMS) announced in June 2008 that it would recognize the NCCN Drugs & Biologics Compendium as a source of information to determine which drugs may be covered under Medicare Part B.
Important ZEVALIN(R) Safety Information
Deaths have occurred within 24 hours of rituximab infusion, an essential component of the ZEVALIN therapeutic regimen. These fatalities were associated with hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, or cardiogenic shock. Most (80%) fatalities occurred with the first rituximab infusion. ZEVALIN administration results in severe and prolonged cytopenias in most patients. Severe cutaneous and mucocutaneous reactions, some fatal, can occur with the ZEVALIN therapeutic regimen.
Please see full Prescribing Information, including Boxed WARNINGS, for ZEVALIN and rituximab. Patients and healthcare professionals can visit for more information.
About ZEVALIN(R) and the ZEVALIN Therapeutic Regimen
ZEVALIN (ibritumomab tiuxetan) is a CD20-directed radiotherapeutic antibody administered as part of the ZEVALIN therapeutic regimen. The ZEVALIN therapeutic regimen consists of three components: rituximab, Indium-111 (In-111) radiolabeled ZEVALIN for imaging, and Yttrium-90 (Y-90) radiolabeled ZEVALIN for therapy. The ZEVALIN therapeutic regimen is a form of cancer therapy called radioimmunotherapy. Radioimmunotherapy (RIT) is an innovative form of cancer treatment with a mechanism of action that is different from traditional chemotherapy. RIT builds on the combined effect of a targeted biologic monoclonal antibody augmented with the therapeutic effects of a beta-emitting radioisotope.
For more information on ZEVALIN, patients and healthcare professionals can visit .
ARRY ACR 50 and ACR 70- This trial seems to be another victim of the placebo effect. Tomorrow's CC slides are available in the link below and it appears based on slide 6 that if placebo had behaved as expected two of the doses would have been stat sig for acr 20. Placebo RR was expected to be 30% but was around 48%.
BTW mcbio the acr50 and 70 RR's are on slide 7. They aren't stat sig either.
http://phx.corporate-ir.net/External.File?item=UGFyZW50SUQ9MTQ1MDJ8Q2hpbGRJRD0tMXxUeXBlPTM=&t=1
SVNT - Savient rises as analyst says buyout possible
Analyst says Savient Pharma could be bought out after meeting with FDA over gout drug
On Thursday September 3, 2009, 1:52 pm EDT
Companies: Savient Pharmaceuticals, Inc.
NEW YORK (AP) -- Shares of Savient Pharmaceuticals Inc. advanced Thursday after a JMP Securities analyst said the company could become a buyout target later this month.
Analyst Liisa Bayko said Savient confirmed it will meet with the Food and Drug Administration in a few weeks to discuss Krystexxa, which is intended to treat chronic gout. In early August, the FDA said it could not approve Krystexxa without more information about the manufacturing process and additional safety data.
Bayko said the meeting should remove some of the risk around Savient's stock, as it will be more clear what the FDA wants Savient to do to gain approval.
Bayko recommended buying the stock, and said the East Brunswick, N.J., company could fetch a takeout price of at least $20 per share.
In afternoon trading, the stock rose 83 cents, or 6.1 percent, to $14.44. The stock has ranged from $2.80 to $22.36 over the past year.
http://finance.yahoo.com/news/Savient-rises-as-analyst-says-apf-3664063896.html?x=0&.v=2
sppi - Options are being traded as if approval is a certainty. 12.50 calls seem pretty popular as well. IF raj does a pipe tomorrow though all bets are off.
arry - Wonder what the CC is for. There isn't too much to discuss in terms of what would happen to the RA program. Trading around 3 after hours.
Study finds potential way to make an AIDS vaccine
Thu Sep 3, 2009 2:30pm EDT
By Maggie Fox, Health and Science Editor
WASHINGTON (Reuters) - The discovery of immune system particles that attack the AIDS virus may finally open a way to make a vaccine that could protect people against the deadly and incurable infection, U.S. researchers said on Thursday.
They used new technology to troll through the blood of 1,800 people infected with the AIDS virus and identified two immune system compounds called antibodies that could neutralize the virus.
And they found a new part of the virus that the antibodies attack, offering a new way to design a vaccine, they reported in the journal Science.
"So now we may have a better chance of designing a vaccine that will elicit such broadly neutralizing antibodies, which we think are key to successful vaccine development," said Dennis Burton of The Scripps Research Institute in La Jolla, California, who led the study.
"The findings themselves are an exciting advance toward the goal of an effective AIDS vaccine because now we've got a new, potentially better target on HIV to focus our efforts for vaccine design," added Wayne Koff of the International AIDS Vaccine Initiative, or IAVI, which sponsored the study.
Since the AIDS pandemic started in the early 1980s, more than 25 million people globally have died from the virus. The World Health Organization estimates that 33 million are currently infected.
There is no cure, although a cocktail of drugs can help keep the virus under control. Efforts to make a vaccine have failed almost completely.
MUTABLE VIRUS
Part of this is because the virus mutates so much that any one person is infected with millions of different versions, each one appearing different to the immune system.
In addition, the virus infects the very immune cells that are supposed to help protect the body. And if even one virus gets past the immune defense, it appears to set up a lifelong infection. No drug has been able to eradicate it.
IAVI director Dr. Seth Berkley said the findings will not lead directly to a vaccine, but show that there are new and better ways to design one.
He said 10 percent of the patients whose blood was screened had a strong antibody response to the virus. "We have people with even more potent serum out there. We will probably see more," he said in a telephone interview.
It may also be possible to use such antibodies as therapy themselves -- such as the gamma globulin used for hepatitis virus. But the eventual goal, Berkley said, is a vaccine that produces antibodies that could stop the virus from ever infecting a person in the first place.
"We haven't been able to do that because we haven't been able to find the right kind of response," Berkley said.
Most vaccines elicit an antibody response, priming the body to make antibodies that will recognize and attack an invader such as a bacteria or virus.
The two antibodies, called PG9 and PG16, are the first new HIV antibodies to have been identified in more than 10 years. They target a region of the spike the virus uses to infect cells, the researchers wrote.
A team at South San Francisco-based Monogram Biosciences Inc screened the blood for the ability to neutralize HIV. Theraclone Sciences used its technology to identify the antibodies involved.
North Carolina-based Laboratory Corp of America Holdings acquired Monogram in July.
(Editing by Eric Walsh)
http://www.reuters.com/article/topNews/idUSTRE5825GO20090903?sp=true
ALTH - I am skeptical that the FDA will make a decision by the 24th and also that a decision will be positive. On one of the two previous occasions the fda granted accelerated approval the results in terms of response rate and duration were a lot better and on both occasions the companies had run two single arm trials.
"The FDA has based some approvals of oncology drugs on single-arm trials, Pazdur noted.
Eisai Inc.'s Targretin (bexarotene) was granted approval for CTCL in 1999 based on response rates of 54 percent and 45 percent in single-arm studies, with response durations of 107 days and 159 days, respectively. Merck & Co. Inc.'s Zolinza (vorinostat) also was given full approval in 2006 on the basis of response rate in two single-arm studies of patients with refractory CTCL, Pazdur added."
http://www.bioworld.com/servlet/com.accumedia.web.Dispatcher?next=bioWorldHeadlines_article&forceid=51977
I listed to the CC yesterday and management stated that they had not submitted any material yet for another clinical trial. I consider that a huge red flag signalling at the very least a huge delay for a decision by the FDA. Given pazdur's prior history with Provenge I can only assume the worst.
ALTH - I believe the EMEA rep was critical of the single arm. However since the FDA signed off on the SPA which permitted the single arm that shouldn't be a problem. Hard to figure this one out. FDA decision may not be a binary event ie another trial before approval or complete approval and the direction of the share price from such a decision is hard to predict IMO. In any case I think its close to being fully valued even on approval.
alth sppi (blade) - whats the theory behind a rise in share price for sppi based on what happened to alth? Zevalin and NHL i assume but i don't see the connection. Also alth is currently halted.
http://www.nasdaqtrader.com/Trader.aspx?id=Tradehalts
ALTH - The comments in this article don't seem too positive.
UPDATE 2-US FDA panel backs Allos' lymphoma drug
Wed Sep 2, 2009 6:34pm EDT
* FDA panel votes 10-4 in support of Folotyn
* Panelists say conflicted but see benefit for some
* Company says pleased with panel's support (Adds comments from meeting, company reaction, byline)
By Susan Heavey
SILVER SPRING, Md., Sept 2 (Reuters) - Clinical data for Allos Therapeutics Inc's (ALTH.O) experimental lymphoma drug Folotyn were not overwhelming but did look promising for a certain group of patients, a U.S. medical advisory panel said on Wednesday in backing the product.
The Food and Drug Administration's panel of outside experts, in a 10-4 vote, said the company's results were strong enough to show patients with an aggressive type of the cancer were likely to benefit.
"This drug is not a home run. It's a base hit. It's not even a double -- it's a single," said panelist Dr. Brad Kahl, a professor at the University of Wisconsin who still backed the drug.
It was enough of a benefit for most panelists, who expressed concern for the small number of previously treated patients with peripheral T-cell lymphoma (PTCL) who have relapsed and have no other options.
The company is expecting the FDA to make its decision by Sept. 24, although the agency has missed several such deadlines in recent months. The FDA will weigh the panel's recommendation before making its final approval decision.
"This was an important step forward," Allos' President and Chief Executive Officer Paul Berns told reporters after the meeting.
PTCL is a less common type of non-Hodgkin's lymphoma, but it can be more aggressive than its B-cell counterpart and affects about 9,500 people in the United States, according to the FDA.
It also accounts for about 10 to 15 percent of the 66,000 new U.S. cases of non-Hodgkin's lymphoma expected to be diagnosed this year, the company also said, citing American Cancer Society data.
The drug aims to camouflage itself as a folic acid so it can be absorbed by the tumor, then attack the cancer.
But FDA officials cautioned the panel that while the drug seems to have some active effect on PTCL, that effect alone is not enough to merit approval.
The agency is weighing Folotyn under an expedited review process in which products must be shown to be better than other treatments. For fuller approval, "we need additional studies here," said Dr. Richard Pazdur, director of the FDA's Office of Oncology Drug Products.
Pazdur and other FDA staff noted that just 27 percent of the trial's 115 patients responded to Folotyn, most only partially. Slightly more than half of those who saw some of benefit responded for less than 14 weeks, they added.
Most panel members said they were conflicted about approval, but company officials won them over by pointing to patients' unmet medical needs. Allos is also studying Folotyn as possible therapy for other cancers, including non-small cell lung cancer and bladder cancer.
"It's a miserable disease with really no good alternative," said panelist Dr. Michael Link, chief of oncology at Stanford University's School of Medicine, who backed Folotyn.
Still, among the four panelists who rejected the drug, concerns remained about how much of an effect it would have given the limited data.
Panelist Dr. Ronald Richardson of the Mayo Clinic said that the number of patients who responded was not "particularly robust" and that he was "underwhelmed" by how long the drug's effect lasted.
(Reporting by Susan Heavey; Editing Bernard Orr)
http://www.reuters.com/article/marketsNews/idINN021997920090902?rpc=44&sp=true
ALTH - Management estimates peak sales to be around 350-450 million at around 70 - 100 K a pop. There appeared to be some serious efficacy concerns that even Adam. F, a big supporter of ALTH, thought it seemed like a close shave. About 90 million shares outstanding so whats a reasonable marketcap.
ALTH - Theres a CC at 6 pm and stock will likely be halted till afterwards.
Placebos Are Getting More Effective. Drugmakers Are Desperate to Know Why.
Interesting article on the placebo effect
Merck was in trouble. In 2002, the pharmaceutical giant was falling behind its rivals in sales. Even worse, patents on five blockbuster drugs were about to expire, which would allow cheaper generics to flood the market. The company hadn't introduced a truly new product in three years, and its stock price was plummeting.
In interviews with the press, Edward Scolnick, Merck's research director, laid out his battle plan to restore the firm to preeminence. Key to his strategy was expanding the company's reach into the antidepressant market, where Merck had lagged while competitors like Pfizer and GlaxoSmithKline created some of the best-selling drugs in the world. "To remain dominant in the future," he told Forbes, "we need to dominate the central nervous system."
His plan hinged on the success of an experimental antidepressant codenamed MK-869. Still in clinical trials, it looked like every pharma executive's dream: a new kind of medication that exploited brain chemistry in innovative ways to promote feelings of well-being. The drug tested brilliantly early on, with minimal side effects, and Merck touted its game-changing potential at a meeting of 300 securities analysts.
Behind the scenes, however, MK-869 was starting to unravel. True, many test subjects treated with the medication felt their hopelessness and anxiety lift. But so did nearly the same number who took a placebo, a look-alike pill made of milk sugar or another inert substance given to groups of volunteers in clinical trials to gauge how much more effective the real drug is by comparison. The fact that taking a faux drug can powerfully improve some people's health—the so-called placebo effect—has long been considered an embarrassment to the serious practice of pharmacology.
Ultimately, Merck's foray into the antidepressant market failed. In subsequent tests, MK-869 turned out to be no more effective than a placebo. In the jargon of the industry, the trials crossed the futility boundary.
MK-869 wasn't the only highly anticipated medical breakthrough to be undone in recent years by the placebo effect. From 2001 to 2006, the percentage of new products cut from development after Phase II clinical trials, when drugs are first tested against placebo, rose by 20 percent. The failure rate in more extensive Phase III trials increased by 11 percent, mainly due to surprisingly poor showings against placebo. Despite historic levels of industry investment in R&D, the US Food and Drug Administration approved only 19 first-of-their-kind remedies in 2007—the fewest since 1983—and just 24 in 2008. Half of all drugs that fail in late-stage trials drop out of the pipeline due to their inability to beat sugar pills.
The upshot is fewer new medicines available to ailing patients and more financial woes for the beleaguered pharmaceutical industry. Last November, a new type of gene therapy for Parkinson's disease, championed by the Michael J. Fox Foundation, was abruptly withdrawn from Phase II trials after unexpectedly tanking against placebo. A stem-cell startup called Osiris Therapeutics got a drubbing on Wall Street in March, when it suspended trials of its pill for Crohn's disease, an intestinal ailment, citing an "unusually high" response to placebo. Two days later, Eli Lilly broke off testing of a much-touted new drug for schizophrenia when volunteers showed double the expected level of placebo response.
It's not only trials of new drugs that are crossing the futility boundary. Some products that have been on the market for decades, like Prozac, are faltering in more recent follow-up tests. In many cases, these are the compounds that, in the late '90s, made Big Pharma more profitable than Big Oil. But if these same drugs were vetted now, the FDA might not approve some of them. Two comprehensive analyses of antidepressant trials have uncovered a dramatic increase in placebo response since the 1980s. One estimated that the so-called effect size (a measure of statistical significance) in placebo groups had nearly doubled over that time.
It's not that the old meds are getting weaker, drug developers say. It's as if the placebo effect is somehow getting stronger.
The fact that an increasing number of medications are unable to beat sugar pills has thrown the industry into crisis. The stakes could hardly be higher. In today's economy, the fate of a long-established company can hang on the outcome of a handful of tests.
Why are inert pills suddenly overwhelming promising new drugs and established medicines alike? The reasons are only just beginning to be understood. A network of independent researchers is doggedly uncovering the inner workings—and potential therapeutic applications—of the placebo effect. At the same time, drugmakers are realizing they need to fully understand the mechanisms behind it so they can design trials that differentiate more clearly between the beneficial effects of their products and the body's innate ability to heal itself. A special task force of the Foundation for the National Institutes of Health is seeking to stem the crisis by quietly undertaking one of the most ambitious data-sharing efforts in the history of the drug industry. After decades in the jungles of fringe science, the placebo effect has become the elephant in the boardroom.
The roots of the placebo problem can be traced to a lie told by an Army nurse during World War II as Allied forces stormed the beaches of southern Italy. The nurse was assisting an anesthetist named Henry Beecher, who was tending to US troops under heavy German bombardment. When the morphine supply ran low, the nurse assured a wounded soldier that he was getting a shot of potent painkiller, though her syringe contained only salt water. Amazingly, the bogus injection relieved the soldier's agony and prevented the onset of shock.
Returning to his post at Harvard after the war, Beecher became one of the nation's leading medical reformers. Inspired by the nurse's healing act of deception, he launched a crusade to promote a method of testing new medicines to find out whether they were truly effective. At the time, the process for vetting drugs was sloppy at best: Pharmaceutical companies would simply dose volunteers with an experimental agent until the side effects swamped the presumed benefits. Beecher proposed that if test subjects could be compared to a group that received a placebo, health officials would finally have an impartial way to determine whether a medicine was actually responsible for making a patient better.
In a 1955 paper titled "The Powerful Placebo," published in The Journal of the American Medical Association, Beecher described how the placebo effect had undermined the results of more than a dozen trials by causing improvement that was mistakenly attributed to the drugs being tested. He demonstrated that trial volunteers who got real medication were also subject to placebo effects; the act of taking a pill was itself somehow therapeutic, boosting the curative power of the medicine. Only by subtracting the improvement in a placebo control group could the actual value of the drug be calculated.
The article caused a sensation. By 1962, reeling from news of birth defects caused by a drug called thalidomide, Congress amended the Food, Drug, and Cosmetic Act, requiring trials to include enhanced safety testing and placebo control groups. Volunteers would be assigned randomly to receive either medicine or a sugar pill, and neither doctor nor patient would know the difference until the trial was over. Beecher's double-blind, placebo-controlled, randomized clinical trial—or RCT—was enshrined as the gold standard of the emerging pharmaceutical industry. Today, to win FDA approval, a new medication must beat placebo in at least two authenticated trials.
Beecher's prescription helped cure the medical establishment of outright quackery, but it had an insidious side effect. By casting placebo as the villain in RCTs, he ended up stigmatizing one of his most important discoveries. The fact that even dummy capsules can kick-start the body's recovery engine became a problem for drug developers to overcome, rather than a phenomenon that could guide doctors toward a better understanding of the healing process and how to drive it most effectively.
In his eagerness to promote his template for clinical trials, Beecher also overreached by seeing the placebo effect at work in curing ailments like the common cold, which wane with no intervention at all. But the triumph of Beecher's gold standard was a generation of safer medications that worked for nearly everyone. Anthracyclines don't require an oncologist with a genial bedside manner to slow the growth of tumors.
What Beecher didn't foresee, however, was the explosive growth of the pharmaceutical industry. The blockbuster success of mood drugs in the '80s and '90s emboldened Big Pharma to promote remedies for a growing panoply of disorders that are intimately related to higher brain function. By attempting to dominate the central nervous system, Big Pharma gambled its future on treating ailments that have turned out to be particularly susceptible to the placebo effect.
The tall, rusty-haired son of a country doctor, William Potter, 64, has spent most of his life treating mental illness—first as a psychiatrist at the National Institute of Mental Health and then as a drug developer. A decade ago, he took a job at Lilly's neuroscience labs. There, working on new antidepressants and antianxiety meds, he became one of the first researchers to glimpse the approaching storm.
To test products internally, pharmaceutical companies routinely run trials in which a long-established medication and an experimental one compete against each other as well as against a placebo. As head of Lilly's early-stage psychiatric drug development in the late '90s, Potter saw that even durable warhorses like Prozac, which had been on the market for years, were being overtaken by dummy pills in more recent tests. The company's next-generation antidepressants were faring badly, too, doing no better than placebo in seven out of 10 trials.
As a psychiatrist, Potter knew that some patients really do seem to get healthier for reasons that have more to do with a doctor's empathy than with the contents of a pill. But it baffled him that drugs he'd been prescribing for years seemed to be struggling to prove their effectiveness. Thinking that something crucial may have been overlooked, Potter tapped an IT geek named David DeBrota to help him comb through the Lilly database of published and unpublished trials—including those that the company had kept secret because of high placebo response. They aggregated the findings from decades of antidepressant trials, looking for patterns and trying to see what was changing over time. What they found challenged some of the industry's basic assumptions about its drug-vetting process.
Assumption number one was that if a trial were managed correctly, a medication would perform as well or badly in a Phoenix hospital as in a Bangalore clinic. Potter discovered, however, that geographic location alone could determine whether a drug bested placebo or crossed the futility boundary. By the late '90s, for example, the classic antianxiety drug diazepam (also known as Valium) was still beating placebo in France and Belgium. But when the drug was tested in the US, it was likely to fail. Conversely, Prozac performed better in America than it did in western Europe and South Africa. It was an unsettling prospect: FDA approval could hinge on where the company chose to conduct a trial.
Mistaken assumption number two was that the standard tests used to gauge volunteers' improvement in trials yielded consistent results. Potter and his colleagues discovered that ratings by trial observers varied significantly from one testing site to another. It was like finding out that the judges in a tight race each had a different idea about the placement of the finish line.
Potter and DeBrota's data-mining also revealed that even superbly managed trials were subject to runaway placebo effects. But exactly why any of this was happening remained elusive. "We were able to identify many of the core issues in play," Potter says. "But there was no clear answer to the problem." Convinced that what Lilly was facing was too complex for any one pharmaceutical house to unravel on its own, he came up with a plan to break down the firewalls between researchers across the industry, enabling them to share data in "pre-competitive space."
After prodding by Potter and others, the NIH focused on the issue in 2000, hosting a three-day conference in Washington. For the first time in medical history, more than 500 drug developers, doctors, academics, and trial designers put their heads together to examine the role of the placebo effect in clinical trials and healing in general.
Potter's ambitious plan for a collaborative approach to the problem eventually ran into its own futility boundary: No one would pay for it. And drug companies don't share data, they hoard it. But the NIH conference launched a new wave of placebo research in academic labs in the US and Italy that would make significant progress toward solving the mystery of what was happening in clinical trials.
Visitors to Fabrizio Benedetti's clinic at the University of Turin are asked never to say the P-word around the med students who sign up for his experiments. For all the volunteers know, the trim, soft-spoken neuroscientist is hard at work concocting analgesic skin creams and methods for enhancing athletic performance.
One recent afternoon in his lab, a young soccer player grimaced with exertion while doing leg curls on a weight machine. Benedetti and his colleagues were exploring the potential of using Pavlovian conditioning to give athletes a competitive edge undetectable by anti-doping authorities. A player would receive doses of a performance-enhancing drug for weeks and then a jolt of placebo just before competition.
Benedetti, 53, first became interested in placebos in the mid-'90s, while researching pain. He was surprised that some of the test subjects in his placebo groups seemed to suffer less than those on active drugs. But scientific interest in this phenomenon, and the money to research it, were hard to come by. "The placebo effect was considered little more than a nuisance," he recalls. "Drug companies, physicians, and clinicians were not interested in understanding its mechanisms. They were concerned only with figuring out whether their drugs worked better."
Part of the problem was that response to placebo was considered a psychological trait related to neurosis and gullibility rather than a physiological phenomenon that could be scrutinized in the lab and manipulated for therapeutic benefit. But then Benedetti came across a study, done years earlier, that suggested the placebo effect had a neurological foundation. US scientists had found that a drug called naloxone blocks the pain-relieving power of placebo treatments. The brain produces its own analgesic compounds called opioids, released under conditions of stress, and naloxone blocks the action of these natural painkillers and their synthetic analogs. The study gave Benedetti the lead he needed to pursue his own research while running small clinical trials for drug companies.
Now, after 15 years of experimentation, he has succeeded in mapping many of the biochemical reactions responsible for the placebo effect, uncovering a broad repertoire of self-healing responses. Placebo-activated opioids, for example, not only relieve pain; they also modulate heart rate and respiration. The neurotransmitter dopamine, when released by placebo treatment, helps improve motor function in Parkinson's patients. Mechanisms like these can elevate mood, sharpen cognitive ability, alleviate digestive disorders, relieve insomnia, and limit the secretion of stress-related hormones like insulin and cortisol.
In one study, Benedetti found that Alzheimer's patients with impaired cognitive function get less pain relief from analgesic drugs than normal volunteers do. Using advanced methods of EEG analysis, he discovered that the connections between the patients' prefrontal lobes and their opioid systems had been damaged. Healthy volunteers feel the benefit of medication plus a placebo boost. Patients who are unable to formulate ideas about the future because of cortical deficits, however, feel only the effect of the drug itself. The experiment suggests that because Alzheimer's patients don't get the benefits of anticipating the treatment, they require higher doses of painkillers to experience normal levels of relief.
Benedetti often uses the phrase "placebo response" instead of placebo effect. By definition, inert pills have no effect, but under the right conditions they can act as a catalyst for what he calls the body's "endogenous health care system." Like any other internal network, the placebo response has limits. It can ease the discomfort of chemotherapy, but it won't stop the growth of tumors. It also works in reverse to produce the placebo's evil twin, the nocebo effect. For example, men taking a commonly prescribed prostate drug who were informed that the medication may cause sexual dysfunction were twice as likely to become impotent.
Further research by Benedetti and others showed that the promise of treatment activates areas of the brain involved in weighing the significance of events and the seriousness of threats. "If a fire alarm goes off and you see smoke, you know something bad is going to happen and you get ready to escape," explains Tor Wager, a neuroscientist at Columbia University. "Expectations about pain and pain relief work in a similar way. Placebo treatments tap into this system and orchestrate the responses in your brain and body accordingly."
In other words, one way that placebo aids recovery is by hacking the mind's ability to predict the future. We are constantly parsing the reactions of those around us—such as the tone a doctor uses to deliver a diagnosis—to generate more-accurate estimations of our fate. One of the most powerful placebogenic triggers is watching someone else experience the benefits of an alleged drug. Researchers call these social aspects of medicine the therapeutic ritual.
In a study last year, Harvard Medical School researcher Ted Kaptchuk devised a clever strategy for testing his volunteers' response to varying levels of therapeutic ritual. The study focused on irritable bowel syndrome, a painful disorder that costs more than $40 billion a year worldwide to treat. First the volunteers were placed randomly in one of three groups. One group was simply put on a waiting list; researchers know that some patients get better just because they sign up for a trial. Another group received placebo treatment from a clinician who declined to engage in small talk. Volunteers in the third group got the same sham treatment from a clinician who asked them questions about symptoms, outlined the causes of IBS, and displayed optimism about their condition.
Rx for Success
What turns a dummy pill into a catalyst for relieving pain, anxiety, depression, sexual dysfunction, or the tremors of Parkinson's disease? The brain's own healing mechanisms, unleashed by the belief that a phony medication is the real thing. The most important ingredient in any placebo is the doctor's bedside manner, but according to research, the color of a tablet can boost the effectiveness even of genuine meds—or help convince a patient that a placebo is a potent remedy.—Steve Silberman
Yellow pills
make the most effective antidepressants, like little doses of pharmaceutical sunshine.
Red pills
can give you a more stimulating kick. Wake up, Neo.
The color green
reduces anxiety, adding more chill to the pill.
White tablets—
particularly those labeled "antacid"—are superior for soothing ulcers, even when they contain nothing but lactose.
More is better,
scientists say. Placebos taken four times a day deliver greater relief than those taken twice daily.
Branding matters.
Placebos stamped or packaged with widely recognized trademarks are more effective than "generic" placebos.
Clever names
can add a placebo boost to the physiological punch in real drugs. Viagra implies both vitality and an unstoppable Niagara of sexy.
Not surprisingly, the health of those in the third group improved most. In fact, just by participating in the trial, volunteers in this high-interaction group got as much relief as did people taking the two leading prescription drugs for IBS. And the benefits of their bogus treatment persisted for weeks afterward, contrary to the belief—widespread in the pharmaceutical industry—that the placebo response is short-lived.
Studies like this open the door to hybrid treatment strategies that exploit the placebo effect to make real drugs safer and more effective. Cancer patients undergoing rounds of chemotherapy often suffer from debilitating nocebo effects—such as anticipatory nausea—conditioned by their past experiences with the drugs. A team of German researchers has shown that these associations can be unlearned through the administration of placebo, making chemo easier to bear.
Meanwhile, the classic use of placebos in medicine—to boost the confidence of anxious patients—has been employed tacitly for ages. Nearly half of the doctors polled in a 2007 survey in Chicago admitted to prescribing medications they knew were ineffective for a patient's condition—or prescribing effective drugs in doses too low to produce actual benefit—in order to provoke a placebo response.
The main objections to more widespread placebo use in clinical practice are ethical, but the solutions to these conundrums can be surprisingly simple. Investigators told volunteers in one placebo study that the pills they were taking were "known to significantly reduce pain in some patients." The researchers weren't lying.
These new findings tell us that the body's response to certain types of medication is in constant flux, affected by expectations of treatment, conditioning, beliefs, and social cues.
For instance, the geographic variations in trial outcome that Potter uncovered begin to make sense in light of discoveries that the placebo response is highly sensitive to cultural differences. Anthropologist Daniel Moerman found that Germans are high placebo reactors in trials of ulcer drugs but low in trials of drugs for hypertension—an undertreated condition in Germany, where many people pop pills for herzinsuffizienz, or low blood pressure. Moreover, a pill's shape, size, branding, and price all influence its effects on the body. Soothing blue capsules make more effective tranquilizers than angry red ones, except among Italian men, for whom the color blue is associated with their national soccer team—Forza Azzurri!
But why would the placebo effect seem to be getting stronger worldwide? Part of the answer may be found in the drug industry's own success in marketing its products.
Potential trial volunteers in the US have been deluged with ads for prescription medications since 1997, when the FDA amended its policy on direct-to-consumer advertising. The secret of running an effective campaign, Saatchi & Saatchi's Jim Joseph told a trade journal last year, is associating a particular brand-name medication with other aspects of life that promote peace of mind: "Is it time with your children? Is it a good book curled up on the couch? Is it your favorite television show? Is it a little purple pill that helps you get rid of acid reflux?" By evoking such uplifting associations, researchers say, the ads set up the kind of expectations that induce a formidable placebo response.
The success of those ads in selling blockbuster drugs like antidepressants and statins also pushed trials offshore as therapeutic virgins—potential volunteers who were not already medicated with one or another drug—became harder to find. The contractors that manage trials for Big Pharma have moved aggressively into Africa, India, China, and the former Soviet Union. In these places, however, cultural dynamics can boost the placebo response in other ways. Doctors in these countries are paid to fill up trial rosters quickly, which may motivate them to recruit patients with milder forms of illness that yield more readily to placebo treatment. Furthermore, a patient's hope of getting better and expectation of expert care—the primary placebo triggers in the brain—are particularly acute in societies where volunteers are clamoring to gain access to the most basic forms of medicine. "The quality of care that placebo patients get in trials is far superior to the best insurance you get in America," says psychiatrist Arif Khan, principal investigator in hundreds of trials for companies like Pfizer and Bristol-Myers Squibb. "It's basically luxury care."
Big Pharma faces additional problems in beating placebo when it comes to psychiatric drugs. One is to accurately define the nature of mental illness. The litmus test of drug efficacy in antidepressant trials is a questionnaire called the Hamilton Depression Rating Scale. The HAM-D was created nearly 50 years ago based on a study of major depressive disorder in patients confined to asylums. Few trial volunteers now suffer from that level of illness. In fact, many experts are starting to wonder if what drug companies now call depression is even the same disease that the HAM-D was designed to diagnose.
Existing tests also may not be appropriate for diagnosing disorders like social anxiety and premenstrual dysphoria—the very types of chronic, fuzzily defined conditions that the drug industry started targeting in the '90s, when the placebo problem began escalating. The neurological foundation of these illnesses is still being debated, making it even harder for drug companies to come up with effective treatments.
What all of these disorders have in common, however, is that they engage the higher cortical centers that generate beliefs and expectations, interpret social cues, and anticipate rewards. So do chronic pain, sexual dysfunction, Parkinson's, and many other ailments that respond robustly to placebo treatment. To avoid investing in failure, researchers say, pharmaceutical companies will need to adopt new ways of vetting drugs that route around the brain's own centralized network for healing.
Ten years and billions of R&D dollars after William Potter first sounded the alarm about the placebo effect, his message has finally gotten through. In the spring, Potter, who is now a VP at Merck, helped rev up a massive data-gathering effort called the Placebo Response Drug Trials Survey.
Under the auspices of the NIH, Potter and his colleagues are acquiring decades of trial data—including blood and DNA samples—to determine which variables are responsible for the apparent rise in the placebo effect. Merck, Lilly, Pfizer, AstraZeneca, GlaxoSmithKline, Sanofi-Aventis, Johnson & Johnson, and other major firms are funding the study, and the process of scrubbing volunteers' names and other personal information from the database is about to begin.
In typically secretive industry fashion, the existence of the project itself is being kept under wraps. NIH staffers are willing to talk about it only anonymously, concerned about offending the companies paying for it.
For Potter, who used to ride along with his father on house calls in Indiana, the significance of the survey goes beyond Big Pharma's finally admitting it has a placebo problem. It also marks the twilight of an era when the drug industry was confident that its products were strong enough to cure illness by themselves.
"Before I routinely prescribed antidepressants, I would do more psychotherapy for mildly depressed patients," says the veteran of hundreds of drug trials. "Today we would say I was trying to engage components of the placebo response—and those patients got better. To really do the best for your patients, you want the best placebo response plus the best drug response."
The pharma crisis has also finally brought together the two parallel streams of placebo research—academic and industrial. Pfizer has asked Fabrizio Benedetti to help the company figure out why two of its pain drugs keep failing. Ted Kaptchuk is developing ways to distinguish drug response more clearly from placebo response for another pharma house that he declines to name. Both are exploring innovative trial models that treat the placebo effect as more than just statistical noise competing with the active drug.
Benedetti has helped design a protocol for minimizing volunteers' expectations that he calls "open/hidden." In standard trials, the act of taking a pill or receiving an injection activates the placebo response. In open/hidden trials, drugs and placebos are given to some test subjects in the usual way and to others at random intervals through an IV line controlled by a concealed computer. Drugs that work only when the patient knows they're being administered are placebos themselves.
Ironically, Big Pharma's attempt to dominate the central nervous system has ended up revealing how powerful the brain really is. The placebo response doesn't care if the catalyst for healing is a triumph of pharmacology, a compassionate therapist, or a syringe of salt water. All it requires is a reasonable expectation of getting better. That's potent medicine.
Contributing editor Steve Silberman (steve@stevesilberman.com) wrote about the hunt for Jim Gray in issue 15.08.
http://www.wired.com/medtech/drugs/magazine/17-09/ff_placebo_effect/?currentPage=all
future of pimavanserin - I agree that the future of pimavanserin in PDP is, for all purposes, dead. The rest of the pipeline is too far along and I expect ACAD to go back to cash levels.
p II stat sig - mcbio I absolutely agree with you. Drugs with strong results in PII appear to perform a lot better during PIII though I believe a recent example to the contrary was AEZSs cetrorelix which I believe did very well in its PII trials. I think though that with sufficient hedging if the reward is well worth the risk it is quite reasonable to invest in stocks like ACAD. In some cases if one does adequate research to figure out what the result of a negative outcome could be then one could even make money from that though it would still be a substantial risk and the amount of money made from a negative outcome is far less than that of a positive outcome.
Four Possibilities for Pharma Firms' Fair Values
With U.S. health-care reform likely on the way, prescription drugs could lose some pricing power in the Medicare market. While highly unlikely, a national plan with strong pricing power controlled by the government could have a significantly negative impact on the value of large pharmaceutical firms.
http://news.morningstar.com/articlenet/article.aspx?id=306352&pgid=rss
Achieving stat sig (95%)for a P II trial is asking for a lot IMO especially since most p II trials normally have small patient samples, and patients are given a variety of doses. In this case the sample size is only 34. If you were to read a similar title for a P III trial then what you say is absolutely true.
ALTH - I posted the FDA briefing document in the message below.
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=41005071
I sold whatever I had after reading this. I think there is a good chance the panel gives the thumbs up because the drug clearly has some effect and PCTL is an unmet need. the FDA did raise some questions on how effective the drug is and also brought up a possible drug related death. Given the small trial size and the questionable response rate anything could happen and I just can't figure out what would happen either way to hedge myself. The panel could give a thumbs up but could recommend a specific PCTL population which could reduce the target population. Thats just a guess on my part.
ACAD CC - Missed part of the call but here are the details I can remember
1) Management has no idea why placebo was so good. They seem to feel though that the drug worked.
2) 2nd trial is going ahead but two trials are required for FDA and once they get more data from the trial will discuss plan with biovail about what to do with the PDP program.
3) Primary endpoint used hallucinations and delusions score and what what I recall the score for hallucunations alone was stag sig. I may be mistaken about that and need to listen to that segment later.
They have a a pretty decent pipeline but nothing immediate. Not sure what to make of the PDP program. I think shares will go down to cash if not lower as selling increases. Inst. ownership was more than 60% and I imagine most will sell.
ACAD - The strategy management adopted to resolve the stat sig issue was to "power" the trial accordingly. I'm not a statistician so "powering" a study is something that I'm still trying to understand fully but it appears that the whatever powering they did was based on the assumption that placebo effect would remain the same as in P II. I think HGSI did a great job with their trial to account for the positive placebo effect and Acadia has not. I'll be interested to find out from the CC why they think the PDP program is not dead yet.
ACADIA Pharmaceuticals Announces Results from Phase III Trial of Pimavanserin in Parkinson's Disease Psychosis - Placebo effect strikes again
Pimavanserin Misses Primary Endpoint of Antipsychotic Efficacy; Meets Key Secondary Endpoint of Motoric Tolerability
Conference Call Scheduled for Today, September 1, at 8:00 A.M. Eastern Time
Press Release
Source: ACADIA Pharmaceuticals Inc.
On Tuesday September 1, 2009, 6:00 am EDT
SAN DIEGO--(BUSINESS WIRE)--ACADIA Pharmaceuticals Inc. (Nasdaq: ACAD - News) today announced top-line results from the first pivotal Phase III trial with pimavanserin in patients with Parkinson’s disease psychosis, or PDP. The study did not meet its primary endpoint of antipsychotic efficacy as measured using the Scale for the Assessment of Positive Symptoms, or SAPS. Pimavanserin met the key secondary endpoint of motoric tolerability as measured using the Unified Parkinson’s Disease Rating Scale, or UPDRS. Pimavanserin was safe and well tolerated, with the frequency of adverse events generally similar in the pimavanserin and placebo arms.
The primary endpoint of the study was the mean change in SAPS scores at day 42 compared to baseline for each of the two pimavanserin treatment arms versus placebo. Patients showed marked improvements in the SAPS scores across all study arms. Mean reductions in SAPS scores were 5.9 points in the placebo arm, 5.8 points in the 10 mg pimavanserin arm, and 6.7 points in the 40 mg pimavanserin arm. Statistical significance was not achieved in either pimavanserin arm primarily due to the larger than expected improvement in placebo-treated patients.
“While we obviously are disappointed with the results of this Phase III study, we continue to believe in the potential of pimavanserin based on our clinical experience to date,” said Uli Hacksell, Ph.D., Chief Executive Officer of ACADIA. “We will thoroughly analyze these data along with the data on other secondary and exploratory endpoints over the next month to better understand the outcome of this study. Meanwhile, we are continuing with the second Phase III PDP trial with pimavanserin.”
Trial Design
The Phase III trial was a multi-center, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of pimavanserin in patients with PDP. A total of 298 patients were enrolled in the trial and randomized to one of three study arms, including two different doses of pimavanserin (10 mg or 40 mg) and placebo. Patients received oral doses of either pimavanserin or placebo once daily for six weeks. Patients remained on stable doses of their existing anti-Parkinson’s therapy throughout the study. The primary endpoint was antipsychotic efficacy as measured using the hallucinations and delusions domains of the SAPS. The key secondary endpoint was motoric tolerability as measured using Parts II and III of the UPDRS.
About Pimavanserin
Pimavanserin is a 5-HT2A receptor inverse agonist in Phase III development as a treatment for Parkinson’s disease psychosis. This new chemical entity, which was discovered by ACADIA, is a small molecule that can be taken orally as a tablet once-a-day. ACADIA and Biovail have formed a collaboration to co-develop and commercialize pimavanserin for neurological and psychiatric indications, including Parkinson’s disease psychosis (PDP) and Alzheimer’s disease psychosis (ADP), in the United States and Canada. ACADIA retains rights to pimavanserin in the rest of the world.
About Parkinson’s Disease Psychosis
According to the National Parkinson Foundation, over 1.5 million people in the United States suffer from Parkinson’s disease. Up to 40 percent of patients with Parkinson’s disease may develop psychotic symptoms, commonly consisting of visual hallucinations and delusions. Currently there is no therapy in the United States approved to treat PDP. The development of psychosis in patients with Parkinson’s disease is associated with increased caregiver burden, nursing home placement, and increased mortality.
Conference Call and Webcast Information
ACADIA will host a conference call and webcast today, September 1, 2009, at 8:00 a.m. Eastern Time to discuss the top-line results from the first pivotal Phase III trial with pimavanserin in patients with PDP. The conference call can be accessed by dialing 866-713-8564 for participants in the U.S. or Canada and 617-597-5312 for international callers (reference passcode 15968327). A telephone replay of the conference call may be accessed through September 15, 2009 by dialing 888-286-8010 for callers in the U.S. or Canada and 617-801-6888 for international callers (reference passcode 88296469). The conference call also will be webcast live on ACADIA’s website, www.acadia-pharm.com, under the investors section and will be archived there until September 15.
http://finance.yahoo.com/news/ACADIA-Pharmaceuticals-bw-3801547176.html?x=0&.v=1
sppi(blade) -
I just don't see how Spectrum can expect much in sales of Fusilev with generic leucovorin on the market.
arry (mcbio) - I see from the last Q that the results are supposed to be out in September. When did management specifically state results would be out this week? TIA
sppi (blade) - What are your thoughts on valuation for SPPI after approval? TIA
New Blood Thinner Matches Warfarin
AUGUST 31, 2009
By RON WINSLOW
A blood thinner being developed by Boehringer Ingleheim GmbH proved to be at least as effective as the workhorse heart drug warfarin in a trial that researchers said could help usher in a new era for preventing stroke in millions of patients with a heart-rhythm disorder called atrial fibrillation.
In an 18,113-patient trial, a high dose of the drug, called dabigatran, reduced the rate of stroke by 34% compared to warfarin, with a comparable rate of major bleeding episodes. With a lower dose, the rate of stroke was similar while the rate of bleeding was similar.
It was first time in a major study that an oral treatment has at least matched warfarin -- a drug that has been on the market for more than a half century -- on both effectiveness and safety, researchers said. An AstraZeneca PLC drug called ximelagatran came close, but failed when it proved toxic to the liver.
"The world has been waiting for more than two decades for a replacement for warfarin and it looks like we have one such medication," said Christopher Cannon, a cardiologist at Brigham and Women's Hospital, Boston, who wasn't involved in the study.
Warfarin, marketed by Bristol-Myers Squibb Co. as Coumadin and available in generic versions, is an anticoagulant that prevents formation of blood clots in the heart of patients with atrial fibrillation -- where they can spread to the brain or lungs with calamitous effects.
It is tricky, however, to maintain the right balance of Warfarin in patients: If the blood gets too thin, there is the potential for causing bleeding in the brain and other problems; if it is too thick, it can lead to clots. Moreover, warfarin reacts with dozens of other drugs and with food such as green vegetables. A patient's genetics can also blunt its effectiveness.
As result, "you have to monitor patients on warfarin at least every month in order to optimize care," said Michael Ezekowitz, a cardiologist at Lankenau Institute for Medical Research, Wynnewood, Pa.. He was a co-leader of the dabigatran study, which was sponsored by Boehringer.
An estimated 3 million Americans have atrial fibrillation, which afflicts about one in 10 people over age 70. Yet because of warfarin's challenges to both doctors and patients, only about half of patients who should be treated are on the medicine, according to some estimates.
In addition to Boehringer Ingelheim's dabigatran, which is on the market in Europe for stroke prevention after hip and knee surgery, at least three other compounds are in or moving into late stages of development as alternatives to warfarin. Johnson & Johnson and Bayer AG's Xarelto is also available in the market in Europe for the surgery indications. Bristol-Myers and Pfizer Inc. are co-developing apixaban. Merck & Co. recently joined forces with Portola Inc. to develop that startup's drug betrixaban.
The dabigatran data were presented Sunday at a meeting of the European Society of Cardiology in Barcelona. They were also published in the New England Journal of Medicine.
In the group given 110 milligrams of dabigatran, the low dose, the rate of stroke and other events where clots were dislodged in the heart and carried to other parts of the body was 1.53% per year, compared with 1.69% for those taking warfarin and 1.11% in the higher-dose, 150-milligram group. Major bleeding episodes occurred in 3.36% of warfarin patients per year, compared with 2.71% for patients on 110 milligrams of dabigatran and 3.11% on 150 milligrams.
If all goes well with Boehringer Ingleheim's approval applications, the drug could win U.S. and European regulatory green lights to treat atrial fibrillation by late next year.
http://online.wsj.com/article/SB125167554221971053.html
Depression and The Recession: Cymbalta Sales Are on the Rise
By Caitlin McDevitt
Sunday, August 30, 2009
During a downturn, we tend to seek the "bright spots" -- sectors or products that are doing well when all the rest are struggling. For example, there were plenty of reports over the past year about retail items -- lipstick, chocolate, and macaroni and cheese -- that were bucking downward trends and selling well during the slump. While these stories were cautiously upbeat, news of an uptick in antidepressant sales despite -- or perhaps because of -- the recession was just plain depressing.
Helplessness, pessimism and persistent sadness -- the main symptoms of depression -- didn't seem to abate as the economy crumbled. About 164 million antidepressant prescriptions were written in 2008, 4 million more than in 2007, according to IMS Health, a health-care information and consulting company.
Antidepressants were the third most prescribed type of drug in 2008, hitting $9.6 billion in sales, up from $9.4 billion the year before. Last month, Eli Lilly reported that second-quarter sales for Cymbalta -- which is on the verge of surpassing Effexor as the nation's best-selling antidepressant -- increased 14 percent over the past year. Our national reliance on these drugs is a stubborn trend. A study published in the August issue of Archives of General Psychiatry found that from 1996 to 2005, antidepressant use in the United States doubled.
Depression may cost the United States as much as $83 billion a year, according to an analysis published in the Journal of Clinical Psychology in 2003. The study found that although costs associated with treatment of depression accounted for $26 billion of the burden, twice that amount -- $52 billion -- was attributed to missed workdays and lost productivity. Not only do depressed workers tend to take more days off, the study revealed, but the symptoms of the illness can also make it difficult to get work done while on the job.
"If you had to write out a list of symptoms that would be highly correlated with bad performance at work, symptoms of depression are almost exactly consistent with where those productivity declines would be expected," said Paul Greenberg, a health economist who led the research and says patients with depression have difficulties concentrating, remembering details and making decisions. Antidepressants are designed to -- and by many accounts do -- curb some or all of these symptoms.
Pharmaceutical companies will be quick to point out the positive effects of these drugs for those whose doctors think they may need them. As it turns out, the business of depression is particularly lucrative. Whereas other costly conditions, such as heart conditions or cancer, tend to strike late in life, most people experience depression when they're much younger, usually between the ages of 15 and 30. Besides setting in early, depressive episodes tend to recur.
Drug companies realize the importance of resonating with customers early and often, in hopes of establishing loyalty from those who need to take the pills over a long period -- so much so that they've been willing to give the pills away. In May, Pfizer announced that it would offer many of its brand-name drugs -- including the popular antidepressant Zoloft -- free to people who had lost their jobs and health insurance. While the campaign was marketed as sympathetic, another aim was probably less charitable: to keep those patients from switching from Pfizer brands to cheaper generics.
Rising reliance on antidepressants doesn't benefit Big Pharma exclusively, though. Drug companies are notorious for big marketing campaigns -- bolstering revenue streams for businesses that rely on those ads.
"Certainly they're contributing big time to advertising revenue," says Charles Barber, author of "Comfortably Numb: How Psychiatry Is Medicating a Nation."
In the first quarter of 2009, as automotive ads -- long the top advertising category in the Unites States -- plummeted by 28 percent, according to Nielsen rankings, pharmaceutical companies' ad spending was more consistent. It still dropped, but only by 11 percent. Drugmakers were the third-biggest spender of ad money in that period. Without those purchases, some media outlets already floundering in the thinned-out ad market would have been much worse off. Because most depression sufferers are women, female-targeted lifestyle magazines get a particular boost from companies pushing antidepressants.
The most important benefit that antidepressants can provide, of course, is to those taking the medications. While the salutary effects are just the relief that some people need, a few skeptics have theorized that the pills may change a person's mind-set too much.
Nearly a decade ago, Randolph Nesse, a professor of psychiatry at the University of Michigan, suggested that investors numbed by antidepressants would take risky bets and make bad decisions.
They may "become far less cautious than they were before, worrying too little about real dangers," he wrote. He predicted that, as more people turned to prescription medications, the collective effect would cause a Wall Street bubble to grow and burst.
Did Prozac cause the most recent market free fall?
Seems like a stretch, but if so, then maybe the "great recession" should have been called a depression all along.
http://www.washingtonpost.com/wp-dyn/content/article/2009/08/28/AR2009082804069.html?hpid=sec-business