Archive for the ‘Uncategorized’ Category.

EYLEA PDUFA Date opinion

Regeneron (REGN) is probably still basking in glory of their recent unanimous recommendation from the Advisory Committee for EYLEA (aflibercept opthalmic solution) Opthalmic Solution for the treatment of age related macular degeneration.  The company should now be directing its focus on the upcoming PDUFA Date of Aug 20, 2011 and anticipating an approval.

Intermezzo PDUFA Date Action

Transcept Pharma (TSPT) reported that FDA issued a Complete response letter  to their resubmission of Intermezzo, a drug indicated for use in treating night time awakening insomnia.  The original NDA was submitted in 2008 and not favorably considered by the FDA because of concerns they had about driver impairment.  The company reported they did a driver impairment study and resubmitted the NDA.  The most recent PDUFA Date was July 14, 2011.

Transcept has reported that the second CRL still has questions about driver impairment.  This doesn’t look good for Intermezzo.  Either the second driver impairment study was inadequate in design (unlikely if the FDA had input and the company followed the FDA input), or it showed driver impairment.  Either case, it looks like another redo of the study.


The PDUFA Date for Astra Zeneca‘s Brilanta is still a ways off, not until July 20, 2011 but we think it’s safe to call this one an approval.  AZN has had it’s problems with this application since the original submission in 2009.  Initially rejected by the FDA for a variety of problems including manufacturing issues, their latest CRL only cited a reanalysis of some of the clinical data and required a post marketing safety plan, REMS.  We think that AZN has probably solved both issues with the FDA.  The earlier approval this year by the European Authorities and the approval earlier this month by the Canadians probably reflects the reanalyzed data.  We wouldn’t be surprised if the approval came before the PDUFA Date.

CONTRAVE Revisited

Yes, we know that all of the bells have tolled for Contrave – even the fat lady’s final notes have faded, but we feel compelled to comment on the Orexigen announcement that they have put their plans for Contrave on hold because they failed to convince the FDA that their plan to study the potential cardiovascular effects was sound.  Equally interesting to us was the comment made that such action by the FDA challenges the development of obesity drugs in the US.

We have been consistent in our opinion of the three obesity drugs that were before the FDA during the past year.  Uniformly, they either didn’t meet the very lenient efficacy requirement or in fact failed it.  Recall our cupcake commentary – 5% weight loss over the course of a year for a 200 pound person is the equivalent of one cupcake a week.  Remember also, it is all about benefit risk with the FDA.  With such a lenient efficacy requirement, it is understandable that the FDA expects a very clean safety profile.

There is a case for the continued evaluation of obesity drugs in the US.  With all the reports confiming that we are a society that is becoming more and more obese, dieting and will power don’t seem to be able to control the trend.  So how about developing a drug that is as effective as gastric by pass with 25% weight loss not uncommon in the year following surgery.  Such a weight loss with the accompanying reduction in co-morbidities associated with obesity may just get the benefit risk to a position that the FDA finds acceptable.

ACUROX opinion

The PDUFA Date for ACUROX is June 17, 2011.  ACUROX is the product of Acura Pharmaceuticals which had an agreement with King Pharmaceuticals which was acquired by Pfizer.  The drug is immediate release oxycodone formulated with ACUROX’s Aversion abuse potential technology.  If you recall, this is not the first time around the track for Acura.  It originally presented a similar product for oxycodone with niacin to the FDA Advisory Committee in April of 2009.  The Advisory Committee was less than impressed and voted it down 19-1.  The FDA followed with a CRL in June of 2009.  The company resubmitted the application without niacin at the end of 2010 and got a Priority Review designation.

We see a couple of obstacles standing in the way of approval this time around.  The first is the unique technology.  It is difficult to judge the usefulness of the technology based on the information available.  To our knowledge, there is no other drug approved that uses the Aversion abuse technology.  A second obstacle is proof offered by the company on its website for efficacy.  It cites a study done by an independent chemist in support of the difficulty in extracting oxycodone from the formulation.  The clinical trials appear to have used recreational “snorters” to test the Aversion technology.  It is difficult for us to assess the resourcefulness of recreational “snorters” vs the more hard core drug abusers in overcoming the obstacle imposed by the Aversion technology.  The third and most significant obstacle to the approval of this drug is the FDA request to the company for robust, long term clinical studies to support the label claim.  The company has commented that these studies are too long and too expensive and they will address the usefulness of the Aversion technology in the product labeling.

We don’t think a package insert statement will satisfy the FDA requirement for robust, long term clinical studies.

SUTENT (sunitinib) Advisory Committee Meeting

On Tuesday, April 12, 2011 the FDA Oncology Advisory Committee will discuss Pfizer‘s application for the use of SUTENT in patients with unresectable pancreatic neuroendocrine tumors.  SUTENT has 2 approved indications, including use in patients with advanced renal cell carcinoma.

Based on the issues raised in the FDA Briefing Document, Pfizer might want to spend some time explaining their regulatory/development strategy.  Specifically, the FDA seems to have challenged the company’s choice of a single Phase 3 study using Progression Free Survival as the end point instead of Overall Survival, especially since Pfizer chose not to avail themselves of an End of Phase 2 meeting with the FDA.  It doesn’t appear that Pfizer got FDA agreement through an SPA either.

The Advisory Committee will probably focus on the conduct of the study though and the role the DMC had in the decision making process other than safety.  The major issue seems to be the halting of the trail with only 28% of the subjects enrolled and the predictive value of this limited number of PFS patients from a single study.

One study with limited enrollment, PFS instead of OS – I think the discussion will be short and predictable.  The recommendation will be negative.


YERVOY (ipilimunab) PDUFA Date

The PDUFA Date of March 26, 2011 is rapidly approaching and Bristol-Myers Squibb is justifiably hopeful that it will mark the approval of YERVOY (ipilimunab) for melanoma.  The FDA gave this drug a priority review status but then delayed the PDUFA Date for 3 months for some reanalyses.  This time should be the charm.  Why?  It’s a cancer drug that shows a survival benefit and that’s the name of the game with the FDA – show me the survival!!

2010 – The Year of the “nyet” to the “diet”

The final shoe has dropped!  In spite of a positive recommendation from the Advisory Committee in December, the FDA has rejected the application for the third diet drug seeking approval in 2010. 

The reaction to this rejection came as a surprise to many in the financial community as evidenced by the run up in the stock price of Orexigen prior to the announcement that it was not favorably considered (NFC).  As I commented after the Advisory Committee, the FDA will always have the final say.  And, it said the benefit risk just wasn’t there.

We’ve had 3 diet drugs fail this year, all because the benefit risk didn’t measure up.  I was thinking that this might be a good time for the FDA to revise the Guidelines for diet drugs – require that the weight loss be more than the “cup cake” effect that I’ve talked about before.  But then I really started thinking about it.  Is 5% weight loss over the course of a year compared to placebo a good target?  Yeah, it probably is given that the folks on placebo are probably going to lose some weight.  So what’s the problem?

I think the problem is that the developers of these diet drugs are focusing too much on meeting the minimum weight loss target of the guidelines and not enough on the overal benefit risk of the equation.  So, what’s the solution?  How about some new rules that they can work towards without the FDA stepping in:
              1.  Set a target weight loss for any new product of greater than 10% for a year.  This improves
                   benefit side of the benefit risk equation for the FDA.  Hey, it might help with marketing the
                   drug too.
              2.  Spend some more time in Phase I and Phase 2 doing some pharmacology studies,
                   especially cardiovascular studies that are designed to provide answers on the tough
                   issues that have plagued these drugs for decades.  Yes, it may knock some of the
                   candidates out early but think of the money you’ll save on Phase 3 studies that shouldn’t
                   have been done.

Bottom line – you’ve heard it here before and you’ll hear it here again, it’s all about benefit risk and writing a package insert that can be approved.

Ezogabine – PDUFA Date follow up

GSK and Valeant announced today that they have received a Complete Response Letter from the FDA that rejects their application for ezogabine for the treatment of epilepsy. This comes after the Advisory Committee recommend approval on August 11, 2011. 
The company releases are not very helpful in defining the reason for the rejection, only citing non-clinical issues that need to be resolved.   There was an earlier postponement of the PDUFA Date, so this may indicate the problem resides in the manufacturing area.  The company releases also indicate that the issues will be resolved in early 2011.

CONTRAVE – Advisory Committee Meeting

On Dec 7, 2010, Orexigen Therapeutics (OREX) will present the data on CONTRAVE to an FDA Advisory Committee seeking its recommendation for use of CONTRAVE  (bupropion SR/naltrexone SR) in the treatment of obesity.

Some may think that a positive recommendation for a diet drug is overdue from this Committee because they have already failed to recommend approval for two other diet drugs just this year.  Those who think that way are mistaken.  We think this Advisory Committee is tuned in to the same wave length as the FDA on these drugs. They will see this as another fixed combination diet drug and look for a positive benefit risk ratio. We don’t think they’ll find one.