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Late last year, GSK said it would release (anonymous) patient level information from clinical trials to allow researchers more access to provide independent analytics.  It is sticking to its guns by endorsing the AllTrials movement to do just that.  GSK also says that it is working on its web porthole that will provide researchers the promised open -- yet secure -- access to trial data.

Glaxo Clashes With PhRMA Over Data Disclosure // Pharmalot.

PhRMA -- which GSK belongs to -- and the Association for British Pharmaceutical Industry however both demur, saying it is a bad idea.  PhRMA claims that this level of disclosure will inhibit trial participants from signing up and also will promote second guessing of regulatory decisions -- both ideas being BAD in their view.

I guess they wouldn't be in favor of instant replay in baseball either?  Oh wait, I got them confused with Bud Selig.

Posted by Bruce Lehr Feb 5th 2013.

 

Take Early Clinical Trial Results with a Grain of Salt

It's official. You can ingnore clinical trial results from R&D and very early stage studies.  Don't be investing ten's of millions of dollars in upfront payments. That's for sure.

A recent study confirms that 90% of early positive studies failed to contnue with such results in late stage trials. In fact, it appears that 98% of follow-on studies that previously saw an early stage "big effect" failed to reproduce it in susequent trials.

The reason almost certainly?  Small sample numbers.  You can't do adequate science with very small samples. The random positive responses tend to distort trial results until you build the numbers in late stage trials.  Surprise, surprise given all the late stage crashes that we've seen over the past several years. I'm sure I could knock you over with a sledge hammer about now. See Fierce Biotech.

Posted by Bruce Lehr Oct 25th 2012.

Was Clint Talking to John about Alzheimer's?

The other shoe that analysts have been talking about for a while now dropped today when Eli Lilly revealed that its Alzheimer drug, solanezumab, missed both its primary endpoints in a Phase III trial. Lilly's Lechleiter had at one time been touting this as an example of the internal R&D pipeline drugs that Lilly is expecting to lead it out of the wilderness.

He had backed off solanezumab as having to be the "saviour" though in the past few months when it became apparent that the drug would be a long shot to achieve it's clinical targets.  This was largely apparent as Pfizer's similar drug bapineuzumab failed earlier this year.

Lechleiter is not giving up yet though as he said their analysis shows the drug may be showing a positive trend in slowing cognitive decline in patients with mild-to-moderate disease. We'll see about that John.

See Fierce Biotech, Pharmalot, and In the Pipeline.

Posted by Bruce Lehr Aug 24th 2012.

Bad (even worse) Week to be a Fabry's Patient

Fabry patients got more bad news yesterday -- as if it weren't bad enough already, given shortages of Genzyme's Fabrazyme in the US due to that company's well chronicled manufacturing problems. In fact, last week an Idaho woman filed a lawsuit against Genzyme, charging that a long-standing shortage of its Fabrazyme treatment for Fabry disease led to the death of her husband two years ago. He would still be living, she claims, if the biotech had not experienced severe and persistent quality control problems that led to a subsequent rationing program. 

On the heels of this, Shire had been encouraged by patients and the FDA itelf to file a BLA to get its Fabry drug Replagel approved in the US.  Now,  Shire says that the FDA has told them they will require more clinical data despite the fact that Replagal has been on the European market for more than 10 years.  

However, Shire says that recent meetings with the FDA indicated additional controlled trials will be required for approval, although safety was not an issue. This comes after the drugmaker last November filed its application with the agency, anticipating a speedy review. However, the added trials will cause “a significant delay” and approval would not occur until “the distant future.”

Analysts called the move "a surprise setback for Shire," according to Bloomberg. A new trial, they added, "would take at least two years and is probably not economically justifiable."  All in all, not good news for Fabry patients.  See Fierce Biotech, Pharmalot, and PharmaGossip.

The only one who may be cheered by this news is Genzyme and its investors as its new US manufacturing facility to produce Fabrazyme was recently approved.  The company can now go back into large scale production.  One might wonder about the timing of the FDA decision given that set of circumstances.

Posted by Bruce Lehr Mar 16th 2012.

Vertex Continues to Run its Hep C Race

Vertex, despite the licensing of its well-received new hep C drug Incivek this year, is still in hot pursuit of an oral treatment for hep c that does NOT require interferon. And, it still wants to show elimination of virus in patients by week 12. 

This week it shared results of a small study that combined Incivek, its developmental drug VX-222 and ribavarin to treat virus genotype 1a and 1 b patients with 83% of those treated showing viral loads below lower levels of quantitation by week 12. Now, it will push on to a phase IIb trial based on that success. It is targeting an NDA submission to the FDA by 2014.

Additionally, not one to rest on its laurels, Vertex is also looking at other non-interferon combination therapies using Incivek, VX-222 and two other nucleoside polymerase inhibitor drugs licensed from Alios, ALS-2200 and ALS-2158. Thus, they hope to stay ahead in the hepatitis C treatment market and defend their current share.

Their stock responded yesterday by jumping 3.4% on the news. See Fierce Biotech and Xconomy.

Posted by Bruce Lehr Feb 24th 2012.

Why is CEO of Onyx smiling?

There is news today that Bayer's new colorectal cancer drug, regorafenib (aka "son of Nexavar') will be submitted to the FDA for approval in 2012. Not only is this a potential blockbuster for Bayer, but this is likely to inspire some smiles at Onyx too. The biotech landed a $160 million payday and won a 20% royalty stake in the drug last fall after prevailing in a bitter dispute over the rights to regorafenib, which bears a close resemblance to the jointly-owned Nexavar. Onyx had accused Bayer researchers of secretly developing analogs of Nexavar before the two partners finally managed to reach an agreement on ownership.

Winning in court and then in the clinic is likely to inspire smiles -- especially for a $160 M plus payday -- and if the analysts are right about the drugs' billion dollar potential the 20% royalty will be worth A LOT.

As Onyx CEO Tony Coles put it, “we are in position to go from one product for two tumors (Nexavar) to potentially three products with strong data or [an FDA clearance] for seven different cancers by the end of this year,” Coles says. The other drug besides Nexavar and regorafenib is known as carfilzomib, which is being reviewed by the FDA as a new treatment for multiple myeloma.

“When you see that kind of momentum in the business in such a short period of time, it’s unrivaled,” Coles says. “We think the future is very bright.”

Say Cheese Tony.

See Fierce Biotech and Xconomy articles.

Posted by Bruce Lehr Jan 18th 2012.

 

BMJ Plays Clincal Data "Hide and Go Seek"

Several sources today reported on British Medical Journal articles that show that not all human trial clinical data is being reported.  Apparently, this is shocking to many clinicians and the public -- but also reflects charges critics have made for years (without the needed proof).

The BMJ is one of a number of journals to take developers to task on their data reporting practices. But despite the new mandates, there's no evidence that the pharma industry is drawing any closer to achieving true transparency. The BMJ concludes that some developers are purposefully keeping some data under lock and key, or publishing it on obscure sites. They want an end to what they call a "culture of haphazard publication and incomplete data disclosure."

These articles confirm the fact that a large proportion of evidence from human trials is unreported, and much of what is reported is done so inadequately. The absence of the data about harm in trials can harm patients, and incomplete data about benefit can lead to wasted costs to health systems. Moreover, researchers or others who deliberately conceal trial results breach their ethical duty to trial participants.

In BMJ, one paper examined unpublished evidence of existing meta-analyses of nine drugs approved by the FDA in 2001 and 2002, but found identical estimates of drug efficacy in only three of 41 cases, or 7 percent.  In the remaining cases, estimates of drug efficacy were evenly split between more (19/41) and less (19/41). Missing data did not always reduce estimates of drug benefits, as this study shows that “publication bias” can cut both ways. Each increment of data can change the overall picture, but in most cases with no certainty that the picture is complete.

Prior registration of all trials became a condition for later publication in 2005.  Yet, a survey of NIH funded research in the United States between 2005 and 2008 shows that only 46 percent of studies were published in a peer reviewed biomedical journal indexed by Medline within 30 months of trial completion. And three years later, one third still remained unpublished.  The law calls for publication of all Government sponsored trial data in 12 months.  Apparently, that doesn't mean much in terms of behavior.

Meanwhile, another paper found that at least 3,000 records of randomized controlled trials entered into Medline between 2006 and 2011 were NOT indexed, which means that many trials will be missed when entering the commonly used research term - randomized clinical trial - into the database. As the authors noted, important evidence in searches - design and methods, baseline characteristics, long term follow-up, and secondary data analyses - can be missed

It's like playing Hide N Seek -- searching all over through documents in regulatory bodies and drug companies to piece data together that should have been freely available. Even when data on individual participants are made available, they only form part of the picture, and Ahmed and colleagues describe the problems of fitting in such data when the whole picture is not known.

Past failures to ensure proper regulation and registration of clinical trials, and a current culture of haphazard publication and incomplete data disclosure, make the proper analysis of the harms and benefits of common treatments almost impossible for systematic reviewers. Patients will have to live with the consequences of these failures for many years to come.

The main challenge is to ensure better systems for the future. This may require the global organisation of a suitable shared database for all raw data from human trials— perhaps the next job for the World Health Organization. Concealment of data should be regarded as a serious ethical breach, and clinical researchers who fail to disclose data should be subject to disciplinary action by professional organisations. This should serve as a wake-up call to both the NIH and the FDA to restrict grants to researchers who receive government funds, but violate the rules. This may achieve quicker results than legislation in individual countries, although this is also desirable. 

See PharmaGossip, Pharmalot and Fierce Biotech reports.

Posted by Bruce Lehr Jan 4th 2012

 

Alnylam Claims 1st with RNAi in Clinic

Today Alnylam reported a preliminary assessment of a small Phase I study (20 patients) showing statistically significant  results in sharply reducing the levels of bad cholesterol in patients suffering from severe hypercholesterolemia. Alnylam also touted the use of second-generation lipid nanoparticles to effectively deliver an RNAi treatment (called ALN-PCS) in this study.

"...we believe is the first ever demonstration of efficacy for an RNAi therapeutic toward a clinically validated endpoint, namely LDL-C, a defined risk factor for coronary artery disease and acute myocardial infarction....," said Akshay Vaishnaw, M.D., Ph.D., Senior Vice President and Chief Medical Officer of Alnylam.

The new drug was well-tolerated at a variety of doses, and no one has dropped out of the study because of side effects, although a mild rash was observed in patients on the treatment, the company said. The study is still ongoing.

Albeit with a very small patient population and in aa early phase I trial, this is the first positive news from the clinic for an RNAi treatment in some time -- and comes on the heels of several Big Pharma players giving up on RNAi last year.  Kudos for now.  See Fierce Biotech and Xconomy.

 

Posted by Bruce Lehr Jan 4th 2012

 

Onyx Submits NDA for Carfilzomib

Onyx Pharmaceuticals submitted its new drug application for its multiple myeloma drug, carfilzomib, to the FDA today, and asked for expedited regulatory review. If approved, this would be Onyx's second cancer drug following in the footsteps of Nexavar (sorafenib) for kidney and lung cancers.

The new drug was acquired from Proteolix and will compete with Millenium's (Takeda) own myeloma drug of the same proteosome inhibitor class. The NDA was based on data from a Phase IIb trial and two Phase III trials remain in progress. About 25% of patients in the phase IIb trial responded to the treatment with tumors shrinking by at least half. This may be good enough for this condition.

Said Ted W. Love, R&D chief at Onyx, "While important strides have been made in treating patients with multiple myeloma in the last decade, this disease remains uniformly fatal, underscoring the need for new treatment options."  See Fierce Biotech and Xconomy.

 

Posted by Bruce Lehr Sep 28th 2011.

 

T-DM1 Generates More Positive Breast Cancer Data

Roche reported more positive data on T-DM1 in its latest breast cancer trial with 137 women. In this study, T-DM1 (aka trastuzumab emtansine) showed a 41% decrease in the progression of disease versus the standard of care -- Herceptin plus Taxotere.  T-DM1 kept patients' tumors from spreading an average of 5 months longer than the standard control. T-DM1 also had only about half the reported side effects and only 25% as many patients dropped out of treatment as the standard due to adverse events. Thus T-DM1 was better tolerated by patients.

This is more good news for Roche and its partner Immunogen in their quest to gain FDA approval for T-DM1, the latest antibody drug conjugate ("empowered antibody") to seek approval.  Thus the empowered T-DM1 appears to work better than its parent Herceptin plus standard chemotherapy.  Immunogen -- responsible for linking emtansine to Herceptin -- stands to gain as well from milestones and royalties when T-DM1 is finally approved.  Phase III results still await but the trend is positive. See Fierce Biotech and Xconomy.

 

Posted by Bruce Lehr Sep 26th 2011.

FDA Panel Recommends Xarelto

There had been speculation earlier this week the J&J and Bayer's new blood thinner Xarelto might run into problems with an FDA advisory panel, when some alleged gaps in its safety data with certain heart patients was raised in a memo by FDA reviewers. 

FDA Panel Recommends The Xarelto Bloodthinner // Pharmalot.

Nevertheless, the FDA advisory panel voted 9-2 to recommend the agency approve the drug.  Xarelto, if/when approved, will be another drug that replaces the old standard warfarin.  It will have competition though from the recently approved Pradaxa from BI and a forthcoming drug from Pfizer and BMS called Eliquis.  Eliquis is supposed to have the best clinical data of the three.

 

 

Posted by Bruce Lehr Sep 8th 2011.

Niche Cancer Drugs Making Inroads

Fierce Biotech reminds us today that new cancer drugs aimed at defined patient niches and paired with a companion diagnostic are starting to see regulatory success in the market.  Yesterday, Pfizer's crizotinib received approval for the treatment of non-small cell lung cancer in ALK+ patients.  It will be marketed under the trade name Xalkori (former consort of Xena Warrior Princess).  It's priced at $115,000 per year and analysts are pegging it to hit $540 million in annual revenues by 2015. 

Similarly, Roche's Zelboraf (vemurafenib) and its companion diagnostic (and $56,000 6-months price tag) were approved earlier this month for the treatment of certain melanoma patients.  It in fact received accelerated approval as the agency appears to be motivated to get these type of targeted therapies on the market. The FDA has now approved 25 drugs so far this year (as compared to 21 all of 2010) and is rolling toward a big year.

With this type of encouragement, Big Pharma can be expected to deliver more targeted therapies (with high prices) to help replace its cadre of expiring broad population blockbusters (e.g. Lipitor) as the drug strategy begins to shift.  I personally hope to see more of these targeted drugs make it to market sooner rather than later.  See Fierce Biotech 1 and Fierce Biotech 2.

Posted by Bruce Lehr Aug 30th 2011.

Pfizer & Bristol Report Apixiban Results

Pfizer and Bristol Myers Squibb reported phase II results on their new bloodthinner apixiban as compared to the standard therapy - warfarin.  Apixiban reduced the risk of stroke or embolism by 21%, major bleeding by 31% and mortality by 11% in atrial fibrillation patients.

Pfizer & Bristol Bloodthinner: And The Wags Say… // Pharmalot.

"You now have a drug that is not only more effective but more safe," said Jack Ansell, chairman of the department of medicine at Lennox Hill Hospital. See Fierce Biotech.

Apixiban (marketed as Eliquis) will now take steady aim at the $9 billion market for bloodthinners.  Analysts say the drug could grab up to 50% share.  It will compete with Boehringer Ingelheim's newly approved Pradaxa and with Bayer - J&J's expected to be approved Xarelto.  A large portion of the $9 billion market would go a long way toward helping Pfizer forget about any of its Lipitor troubles as that drug comes off patent and faces heavy generic competition.

Posted by Bruce Lehr Aug 30th 2011.

Bydureon Goes to the Heart of the Matter

If at first Bydureon don't succeed, then try try again.  Well, the last time Amylin, Alkermes and Lilly submitted their package to the FDA to gain approval for Bydureon -- as a oonce-weekly version of Byetta -- it was not accepted.  The FDA wanted more studies to determine whether the drug caused heart problems.

The companies announced recently that a new study failed to find an issue with heart rhythms.  Now they plan to resubmit their application (for the third time!) to gain the agency's approval.  Here's betting that a third time will be a charm. See Fierce Biotech.

Posted by Bruce Lehr July 29th 2011.

Roche Readies Approval Request for Combo Breast Cancer Therapy

Roche reported hitting its primary endpoint in the latest test of its antibody, pertuzumab, used in combination with Herceptin and docetaxel for the treatment of Her2-positive breast cancer patients. The combination therapy reportedly worked better than Herceptin and docetaxel alone as measured by progression-free survival (PFS). 

Roche says it plans to file for approval with the FDA before the end of 2011.  Some industry analysts, however, questioned whether PFS improvements alone would be enough to sway the FDA to approve without more data on overall patient survival.

With pertuzumab, Roche has at least found a new way to target Her2 (found in about 25% of breast cancers).  It is the same receptor that Roche's other drug Herceptin targets but hits a different region of the receptor for a multi-pronged attack of the cancer.  Combination therapies of mutliple antibodies and/or chemotherapeutic agents are becoming a more predominant means of attacking cancers. See Fierce Biotech.

 

 

Posted by Bruce Lehr July 15th 2011.

Sanofi MS Drug (from Genzyme) Advances

Sanofi reported yesterday that it had good news from the latest phase III trial with its MS drug, Lemtrada.  Lemtrada, you will remember, was the star player in the Genzyme-Sanofi valuation discussion and the main object of the contingent value rights (CVR) ultimately  crafted to close the deal.

In the latest news from the clinic, Lemtrada was compared to Merck's Rebif in the treatment of multiple sclerosis and patients showed a 55% reduction in relapse rates over  a two-year period. Surprisingly though, the drug fell short in showing a statistically signficant reduction in disability rates.  Sanofi still plans to press ahead with filings for regulatory approval in the USA and EU in early 2012.  See Fierce Biotech.

 

 

Posted by Bruce Lehr July 12th 2011.

New Bydureon Safety Data Should Please FDA

Lilly, Alkermes and Amylin report that the latest safety data ordered by the FDA on Bydureon show that the drug does not cause heart problems even at high doses.  Specifically, Bydureon in the latest tests caused no QT prolongation in the healthy test subjects.  This is good news for Bydureon's chances at approval in the US. It was approved already in Europe last month.

Bydureon is a once-per week treatment for the control of type II diabetes.  Analysts have previously estimated that it could reach peak sales of $2.4 billion by 2016.  The companies will be submitting the new data to the FDA by September. Amylin and Alkermes, in particular have much to gain when the drug finally is approved for use in the US. See Xconomy.

 

Posted by Bruce Lehr July 8th 2011.

J&J's Xarelto Passes FDA Scrutiny

J&J's Xarelto has been approved by the FDA for the treatment of venous thromboembolism (VTE) in a unique oral formulation that is taken once per day. The Company considers it one of its top 6 candidates in the pipeline and analysts believe it is poised to take a healthy share of what could be a $20 billion market.  The current market standard, warfarin, has been in practice for more than 50 years but has safety issues that could be improved upon by the newer competitors coming to market now.

J&J's approval -- though delayed for a couple years in the FDA -- still places it ahead of rival Pfizer's efforts with its own Factor Xa inhibitor, apixaban.  The head starts may be worth millions in the market place.  J&J is also pursuing additional applications for Xarelto -- the next being the prevention of strokes in patients suffering from atrial fibrillation. See Fierce Biotech.

 

 

Posted by Bruce Lehr July 5th 2011.

Sanofi Phase III Success with GLP-1 Drug for Type 2 Diabetes

Sanofi says its GLP-1 drug, lixisenatide, performed well again in its latest phase III trial with Type 2 diabetes patients.  The drug used in combination with Sanofi's Lantus (insulin) significantly lowered patient blood sugar levels and resulted in weight loss.

Analysts say that Sanofi is now positioned to have a potential blockbuster on its hands. The new drug will be marketed as Lyxumia when approved. See Fierce Biotech.

Posted by Bruce Lehr May 31st 2011.

 

 

Novartis Will Get Your Gout

 Novartis announced good results in two phase III clinical trials for its new gout drug called - canakinumab or ACZ885 and branded Ilaris.  In the trials, Ilaris reduced patients pain and prevented subsequent gout attacks as compared to the steroidal standard of care. 

http: Novartis-canakinumab-shows-benefits-in-two-phase-iii-gouty-arthritis-studies/.

Analysts say Ilaris has a decent shot at achieving blockbuster status if the drug can be extended into other anti-inflammatory applications based on its inhibition of IL-1 beta.  Novartis is looking to establish additional indicatins with systemic juvenile idiopathic arthritis, cardiovascular disease, diabetes, and chronic obstructive pulmonary disease (COPD). 

Novartis management continues to tout its strategy of establishing the efficacy of a drug in a narrow niche to gain initial approval and then to extend to other indications where similar anti-disease mechanisms will be effective.

Said Professor Alexander So, University Hospital in Lausanne, "Scientists have only recently learned that the root cause of pain in gouty arthritis is interleukin-1 beta.  Through specifically targeting interleukin-1 beta, these studies show ACZ885 can effectively treat painful attacks while extending the time to new attacks."  See WSJ and Fierce Biotech.

 

 

Posted by Bruce Lehr May 26th 2011.

Abbott's HUMIRA® Meets Endpoints In Phase III Ulcerative Colitis Study

Abbott's HUMIRA® (adalimumab) met its primary endpoint of clinical remission in a Phase III study of adult patients with moderate to severe ulcerative colitis (UC).  Ulcerative colitis (UC) is a chronic autoimmune disease that causes inflammation and ulceration in the lining of the colon or large intestine. It is estimated that approximately 700,000 people in the United States have UC.

Abbott's HUMIRA® (Adalimumab) Meets Primary Endpoints In Phase III Ulcerative Colitis Study.

"People living with ulcerative colitis currently have very few treatment options to help them manage their disease," said Eugene Sun, M.D., vice president, Global Pharmaceutical Clinical Development, Abbott. "We are encouraged by these study results with HUMIRA and the potential they may have for patients."

HUMIRA is not currently approved for the treatment of UC. Abbott recently submitted applications to both the U.S. Food and Drug Administration and the European Medicines Agency seeking approval to market HUMIRA for the treatment of moderate to severe UC.  Currently, HUMIRA is approved to treat conditions like rheumatoid arthritis and ankylosing spondylitis -- and it is one of the lead selling biologics in the world.

 

Posted by Bruce Lehr May 21st 2011.

Phase II Clinical Trial Failures Are Rising

If at first you don't succeed, you stop the trial in phase II -- apparently.  Phase II failures are on the rise with only an 18% success rate in 2008-2010 versus 28% seen in 2006-2007.

Phase II Clinical Trial Failures Are Rising // Pharmalot.

A recent report published in Nature Reviews Drug Discovery examined the fate of 108 phase II development failures between 2008 and 2010.  The results showed:

• 87 of 108 reported a reason for the ceased phase II project
• 44 of 87 stopped due to inadequate efficacy
• 25 of 87 stopped due to "strategic reasons" (we shall return)
• 17 of 87 stopped due to safety concerns
• 21 reported no reason

The study concluded that "strategic reasons" was likely code for inadequate differentiation from more advanced drugs on the market.  This likely occurs as too many companies are chasing too few of the same targets.  Similarly, it is suspected that the 21 with "no reason" reported also represents instances of too little differentiation from more clinically advanced products as 17 of the 21 were with validated targets.

The authors also believe that recent M&A activity, subsequent "rationalization" of the pipeline and the need to "manage R&D costs" further accelerated the phase II plug pulls. Perhaps optimistically, the authors say the trend toward more research with rare diseases (novel targets) and greater emphasis on patient stratification (companion diagnostics anyone?) will help slow this phase II decline. Also, business models that emphasize external partnering and formation of consortia to lay off risk will be beneficial too.

Posted by Bruce Lehr May 11th 2011.

Lucentis vs Avastin - Poster Child for Comparative Effectiveness

The results are in for a trial known as CATT that compares Lucentis and Avastin in the treatment of macular degeneration.  Drum roll please!  To the surprise of very few, Avastin appears to be just as effective in treating the disorder (based on vision testing) as the much more costly Lucentis.  Another year of follow up may show something -- but don't hold your breath.

The NEJM published the results and editorialized:

Health care providers and payers worldwide will now have to justify the cost of using ranibizumab [Lucentis].  Regulators in certain countries will be forced to reconsider policies that make it illegal to use drugs off-label, particularly when so many of their citizens cannot afford ranibizumab.

Let's see, it's $23,400 per Lucentis patient per year versus $595 per Avastin patient per year with same level of improvement in vision.  Multiply difference by 250,000 patients treated annually in US and you have a cool $5.7 billion -- yikes!   Hmmmm - we might save $5.7 billion. Which one should we pick?  I wonder.  See In Vivo blog, Examiner.com and In the Pipeline.

Lucentis is the first Poster Child.

Posted by Bruce Lehr May 4th 2011.

Pfizer Walks Tightrope with Potential Blockbuster RA Drug News

Pfizer reported on Friday that it has seen 4 patients die in a phase III trial with its new rheumatoid arthritis (RA) drug, tofacitinib.  Pfizer's shares dropped 3% and Abbott who markets a rival, Humira, went up 2% on the news. Pfizer is managing the news of the trial carefully as a result -- it says trial researchers only attribute one of the four deaths to the drug.

The results from the current trial, which will be presented at the annual meeting of the European League Against Rheumatism in May, are difficult to interpret because the number of patients who received a placebo is much smaller than those who got tofacitinib. Two of the deaths, a brain trauma and a case of rheumatoid arthritis that worsened after treatment was stopped, are clearly not linked to the drug. A third, a case of respiratory failure, was linked to tofacitinib by researchers.

What’s generating the most discussion is a death from acute heart failure. The researchers in the trial did not link this death to tofacitinib, but it according to Wells Fargo analyst Larry Biegelsen it is the fourth death of a patient from heart failure.  The Food and Drug Administration is likely to pool heart failure deaths when it looks at tofacitinib.

The two key questions are whether tofacitinib will be approved, and whether it will compete directly with the existing injections (a bigger market) --  drugs like Humira, Enbrel, and Remicade or Simponi?  Or will be used in patients who failed them (still a big market) as an oral dose alternative?  This could be a multi-billion dollar question over the lifetime of the drug and one worthy of information management. See the Forbes blog.

 

 

Posted by Bruce Lehr April 25th 2011.

 

Next Alzheimer's Hope Step Forward

There is some buzz in the news today about an eagerly awaited Alzheimer's drug, bapineuzumab, as it progresses in a pivotal phase III trial. The drug is being developed by Elan/J&J and Pfizer. The popular press is touting the drug as a potential - 1st drug - to treat Alzheimer's rather than just ameliorate symptoms for relatively short periods.  It may be the first drug approved that can delay or prevent disease progression.  It does this by binding the amyloid beta protein.  We'll see as the trial results become available as to its effectiveness.

I can understand the anxiousness involved with possibly having an actual treatment for Alzheimer's but I think people need to keep perspective until the trial results are available to assess that it actually works -- or on which sub-populations it actually works. Alzheimer's is a tough area.  Just this past summer, Lilly's semagacestat went down and out in a pivotal phase III trial.  This drug too was aimed at preventing amyloid beta plaques --  though it is a gamma secretase inhibitor and worked by blocking an amyloid forming enzyme. 

Bapineuzumab is a mAb that works by binding a soluble form of the amyloid beta protein in the blood.  Thus, has a different mechanism of action from semagacestat.  Lilly does have another direct rival drug to bapineuzumab, called solanezumab, that is also in pivotal phase III trials.  Solanezumab puportedly will work with a wider patient sub-population and has a somewhat better safety profile though that too needs to be proven by the trial data. See Fierce Biotech and The Daily Mail.

Both newer drugs are touted as mega-blockbusters with peak revenue predictions ranging to the $3 billion plus annually.  However, both need to make it through their respective trials and to market through the appropriate regulatory agencies.  Until then, let's keep our enthusiasm tempered. See Investor Village link to Datamonitor report.

 
Posted by Bruce Lehr April 25th 2011.