Posts tagged ‘William Kennedy’

Durata Therapeutics – dalbavancin

Hello All!  I’m Dan Heathwood and this is my first post with PDUFADATE.com.  I am excited about this venture for a couple reasons.  First, I get to address a pretty big audience.  This site still gets thousands of unique visitors every month even though there hasn’t been a post in nearly two years.  Second, I get to pick Dr. Kennedy’s brain on events that I am interested in before anyone else does, including hedge funds, private equity groups and private investors.  To me that is an incredible edge!

Now for the good stuff.  Durata Therapetics’ dalbavancin.  There’s not too much to this opinion.  I will quote Dr. Kennedy after he read the FDA briefing document, “This is a no brainer”.  I will take it a step further. The approval of this drug is a virtual guarantee.  It’s already been recommended 12-0 by the AdComm in March. Let me repeat 12-0. And there has been so much written about this drug and it’s effectiveness that I don’t know how to condense it into a short post.  It’s simple, if it’s an effective drug it will be approved and dalbavancin is effective.

I will stop riding Kennedy’s coattails and bring some value to this post as well.  So we all know dalbavancin will be approved. Now what?  How am I going to trade this?  After a run-up to  $16.65 in March in anticipation of a positive AdComm outcome, the stock pulled back a little and dipped below $12 for short stint in April.  I wish I could say this is when I jumped on the band wagon but I did start buying a little bit later so I am still pretty pleased with myself.  However, I was advising my friends that they should buy up to $15.00    At $15 I was confident I would be getting at least 10-15% return on my investment. You need to make sure you make a decent profit for the risk you taking and at $15 I didn’t think it was a risk at all.

As I write this DRTX is trading over $17.  To be blunt, at $17 this stock is oversold.  If you’re not in it now I think you missed this one.

We’re Back!

After a long hiatus, we are pleased to announce that we will begin posting opinions about FDA events again.  We also would like to announce the addition of  two new contributors to our site, Dan Heathwood and Tim Shields.  Both are private investors with previous experience working as research analysts for some well known investment firms.  Their past contributions outside of pdufadate.com  have  helped translate our opinions into sound stock trading advice.   Our first post will probably deal with Durata Therapeutics (DRTX) as we continue to receive numerous emails about dalbavancin.

There will be lots of changes to our site so keep checking back.

Information Requests

My webmaster is really excited these days.  He just looked at the numbers for June and the number of visitors we had for the month is incredible.  He also tells me that he has been receiving a large number of requests, some very specific, about QNEXA probability of approval.

We started this website 2 years ago with the idea that we would provide information free of charge for a while to see if there was any interest, determine what specific information our audience wanted and establish some credibility before deciding if we wanted to commercialize the website.  We’ve far exceeded our 3 goals as measured by visitors and feedback.  Unfortunately, we weren’t able to convince any of you to purchase a subscription when we offered and just a few lucky folks have purchased our special reports, thus making the business part of this venture a disappointment.  This is especially disappointing in light of the number of specific, very detailed requests we are getting for additional information that will be used to make decisions that will make you and your clients a lot of money.

If you have questions about QNEXA, I refer you to our website archives or invite you to purchase our special diet report.  I will not be adding any additional comments on the website.

If you still have questions, please consider scheduling a personal discussion.  The fee for such consultation is $100 per quarter hour.

QNEXA Advisory Committee 2012

On Wed, Feb 22, 2012, the Metabolic and Endocrine Advisory Committee will meet once again to discuss the Vivus QNEXA NDA for the treatment of obesity. This Advisory Committee met in July of 2010 to discuss this same NDA.  Several members of the earlier Advisory Committee are returning either as full AdComm members or as temporary members.

The 2010 AdComm voted 6 to 10 against recommending approval for QNEXA.  The reasons given were primarily safety concerns in the areas of neurological/cognitive, cardiovascular, metabolic acidosis and teratogenicity and the need for studies in a broader population of patients.  The sponsor has responded to the concerns raised and has included a 1 year extension of one of the pivotal Phase 3 studies which measured both efficacy and attempted to address the safety concerns.

 Efficacy

This is another example of a company doing more and proving less.  The one year extension study was flawed.  The FDA stated that the selection process for patients entering the study was biased and the results should be considered “observational”.  None the less, the observation made is that there is no benefit from continuing patients beyond one year on QNEXA because even on the highest dose, patients start to regain the weight they lost in the first year.

Safety

NOTE: At 2010 AdComm, the Committee consistently noted that for each of the concerns they had, the risk in a broader population was unknown.  The new 2 year data do not represent a broader population but rather a subjective selection of patients from the 1 year study, the results of which the FDA calls “observational”.  I think “observational” means “we’re sorry you took the time to assemble these data because we had to take the time to “look” at it”.

Metabolic acidosis.  2 year safety cohort showed same reduction in serum bicarbonate.

Cardiovascular risk.  The FDA concluded that while the results were “directionally favorable”, its unknown what would happen in a high risk population or during chronic use.  Sounds like a limited indication, if approved at all, and more work to be done.  But what kind of work?  We won’t know and the sponsor won’t know until after the March AdComm which will be addressing the specific issue.

Suicidal/cognitive effects. 2 year extension did not report any additional concerns about suicidal tendency.  Probably didn’t answer original questions either.  The incidence of cognitive related adverse events was the same in the 2 year study as reported in the 1 year study.

Teratogenic effects.  There is no doubt, the topiramate component of QNEXA is a teratogen.  The sponsor agreed and amended the application to provide for a warning against use by women of child bearing potential.  The FDA responded with the rejection of their proposed labeling.  Why?  Probably several reasons.  One of which is if they excluded women of child bearing potential, the pivotal trials would be invalid as the majority of patients in the studies were women.

I’m surprised that the bulk of the questions from the FDA focus on the teratogenic effect.  I’m surprised that the Risk Management review says that this is a concern for the patients taking topiramate for epilepsy.  What is the problem people?  Go back to FDA 101 – its all about benefit risk.  Topiramate for epilepsy has one benefit risk while topiramate for obesity has another benefit risk.  As a fraction, the former is 10/5 while the latter is 1/5.   But that’s a problem for the FDA to work out for approval.

For the Advisory Committee, lets summarize, comparing what we knew after 2010 and what we know now:

-efficacy – no improvement in weight loss in second year, in fact, weight gain.

-metabolic acidosis – no new data, its still an unknown in broader population

-suicidal/cognitive – no new data, its still an unknown in broader population

-cardiovascular – no new data, its still an unknown in high risk patients and broader population

-teratogen – no new data and company acknowledges teratogenicity.  Risk management program currently seems less stringent than controls the sponsor used in controlled clinical trials and they couldn’t make that work.

I doubt the Advisory Committee will be as generous with the “yes” votes as they were in 2010.

XGEVA (denosumab) Advisory Committee Meeting

On Wed, Feb 8, 2012 the FDA Oncology Advisory Committee will discuss Amgen‘s supplement to their approved BLA for XGEVA (denosumab) for treatment of men with castrate-resistant prostate cancer at high risk of developing bone metastases.

This Advisory Committee discussion and the ultimate FDA approval decision comes down once again to the basic benefit risk decision.  On the benefit side, treatment with denosumab did not result in an improvement in overall survival or progression free survival but it did improve bone metastasis-free survival (BMFS) and time to first bone metastasis, both by about 4 months.  On the risk side, the incidence of osteonecrosis of the jaw with denosumab increased by about 5%.  So, the basic benefit risk question is does the 4 month improvement outweigh the 5% increased risk?

The other significant question raised by the FDA appears to boil down to whether treatment with denosumab in this setting offers any advantage versus “prevention of skeletal related events in patients with solid tumors metastatic to bone”, the approved indication.

The FDA review appears to be on the negative side of neutral.  While the company met the primary endpoint, the FDA review points out that at meetings with the company, the FDA noted that “overall survival, patterns of metastases, and the development of symptomatic metastases will be important review issues”.  There was no advantage in overall survival.  Also, of significant note is the statement in the FDA review that the study was not conducted under a Special Protocol Assessment, meaning there is no “contract” for approval just because the primary endpoint (improvement in BMFS) was met.

XARELTO (rivaroxaban) Advisory Committee Meeting

The application for XARELTO (revaroxaban), the J&J drug that was developed for it’s anti-clotting properties in preventing strokes is to be reviewed by the FDA CardioRenal Drug Advisory Committee on Thursday, Sept 9, 2011.  Those interested in the FDA view of the application need read no further than the summary of the FDA Briefing Document to learn that the FDA Medical team has significant reservations on both the safety and the efficacy of this drug.  How significant you ask?  So significant that if I were advising the company, I’d tell them to cancel the Advisory Committee meeting.  The FDA review started with a comment about readiness to issue a Complete Response Letter, that’s how serious!  The FDA review has requested at least one additional study, that’s how serious.  The FDA has said that any drug that expects to compete with Warfarin in these patients better be as good as Warfarin, that’s how serious.  It looks like the FDA thinks that XARELTO performs at less than 70% of the efficacy of Warfarin.

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.

BRILANTA PDUFA Date

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.