Posts tagged ‘PDUFA’

BELVIQ (lorcaserin) Approved

My webmaster tells me that we have had a record number of visitors to our website this week. Thank you all for visiting us. I suspect many of you were looking for some last minute comments before the June 27, 2011 PDUFA Date for lorcaserin. I didn’t post anything because I had nothing new to add. As I had said in the past, I thought Arena (ARNA) had a better chance of getting approval for LORQESS than did Qnexa because the cardiac problems could be monitored and managed while the teratogenicity issue with Qnexa was binary, ie, all or nothing on the teratogenic effect.

Well, Arena is rejoicing and ringing the BELVIQ! (nee LORQESS). The folks at Vivus (VVUS) and probably some of the analysts are seeing the BELVIQ approval as a sure sign that an approval for QNEXA is just around the corner. I say not so fast. If you remember, a major concern expressed here and raised by some at the Advisory Committee meeting was whether women of child bearing potential who were overweight would heed the warning to avoid getting pregnant, especially in light of the number of women in the QNEXA controlled clinical trials who became pregnant.

Well, those clever folks at FDA added a couple of things to the BELVIQ approval that might do two things. The first is a warning that women of child bearing potential should not take BELVIQ. If I were FDA, I’d try and find a way to monitor how many women and their physicians paid attention to that warning. Should be relatively easy to collect that information. If they find a significant pregnancy rate in women taking BELVIQ, they know the warning is not enough – all this done without jeopardizing an unborn child. The second thing that the FDA did was to recommend that the DEA assign a control classification to BELVIQ. Whether the DEA will do this is unknown at this time. If they do, there is a made to order distribution control for QNEXA should they decide to do it.

If your looking for the bottom line that I normally provide, this is it – if I had to lose 40 pounds in 2 years and had only the choice of waiting for QNEXA or diet, I’d start giving up the cupcakes tomorrow!

The Last Days of the Diet Drug Dilemma

Those of you who read our Special Report on Diet Drugs got a heads up on both the extension of the QNEXA PDUFA Date and the easy time that LORQESS had with the FDA Advisory Committee last week.  But now it’s crunch time and the folks at Vivus and Arena Pharmaceuticals are supplementing their diets with fingernail sandwiches.  Arena has the shorter wait at this time, June 27, 2012 is still their PDUFA Date for LORQESS.  By virtue of the extension, Vivus has to wait until July 26, 2012.

Neither the FDA nor the Advisory Committees have questioned the efficacy of either drug.  Neither set of reviewers have tried to say one is more efficacious than the other.  I agree and would call them equally efficacious.

Both drugs have reported or perceived cardiovascular side effects.  According to the Advisory Committee earlier this year, such drugs should be required to have cardiovascular studies performed before approval.  However, both drugs were submitted for approval and under review when the recommendation, and it is only a recommendation, by the Advisory Committee was made.  That being said, the FDA has a certain degree of leeway in forcing this requirement as an approval requirement.  In my opinion, the FDA will give both companies a break and allow the required study to be done as a condition of approval.  It will be the most closely watched event since the OJ trial.  One might think that QNEXA has the leg up on this because they went to the Advisory Committee first, but in this case, one would be wrong.  Both companies got the information at the same time – from listening to the Advisory Committee live and in person.  Who has the edge on having the protocol in final form?  I don’t know and neither does anyone else except maybe the FDA and I heard they ain’t talking.

FDA doesn’t have to talk about the cardiovascular protocol race because the race isn’t about the cardiovascular side effects, its about the teratogenicity risk.  FDA is breathing a sigh of relief with the data from Arena and the positive vote from the Advisory Committee for LORQESS.  The pressure is off – they have a viable diet drug alternative to QNEXA to satisfy those screaming for a new drug.  And they have an alternative that is not a teratogen.  Even if LORQESS gets an extension of the PDUFA Date from FDA to tidy up their cardiovascular study protocol, they will still be ahead of Vivus who has a somewhat longer struggle with the teratogencity issue.

Diet Drug Special Report is Available

With the Vivus‘ QNEXA PDUFA scheduled for April 17,2012, we have created a special report that reexamines all of the obesity drugs that have been reviewed by the FDA and the Advisory Committee since 2009 to determine if any additional insight could be gained regarding the expected action the FDA will take on QNEXA. The report can be purchased by clicking here or by going to http://www.pdufadate.com/premium-reports.

We changed our automated delivery method with the NORTHERA report so when you do purchase the Diet Drug Special Report, please make sure your spam filter accepts email from pdufadate.com.

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.

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!!

BENLYSTA – Advisory Committee Meeting and PDUFA Date

On November 16, 2010, the FDA Arthritis Advisory Committee will review the BLA for BENLYSTA, the first new drug for lupus in decades.  There’s been a lot of hype about this drug from Human Genome Sciences and Glaxo Smith Kline.  The BLA was submitted on June 10, 2010 and the FDA gave it a Priority Review Status.  All seemed to be going well and in September 2010, Glaxo reported that it was preparing for launch.

Now the FDA has called for an Advisory Committee meeting to review the application and address some significant questions, questions that regardless of the answer, raise some serious questions about an overwhelming endorsement of the drug by the Advisory Committee and indeed may result in a Complete Response Letter on December 9, 2010 rather than an approval.

Here are the issues as laid out by the FDA Briefing Document that are raising the caution flag for us:

 Efficacy:

  • Efficacy of a lupus drug is determined by scores contributed from a number of organ systems.  The  overall positive BENLYSTA data are driven by high response rates in musculoskeletal and mucocutaneous system scores while having little effect on organ systems associated with poor outcome and mortality.
  • The FDA states there is a lack of efficacy in African Americans.
  • The efficacy of BENLYSTA appears to be less in patients in North American trials (US and Canada) than other regions.

  Safety:

  • There appears to be an increased risk of some adverse expereinces including malignancy, suicide and suicidal tendencies and death on patients taking BENLYSTA.

It is important to note that BENLYSTA is given on top of current standard therapy for lupus, so there is little increased benefit (even less for US patients and none for African Americans) over standard therapy and an increased risk over standard therapy.  Looks like overall benefit risk for US patient population is decreased.

While a package insert could be written to work around most of the shortcomings that have been cited by the FDA, such as “relief of musculoskeletal and mucocutaneous symptoms associated with lupus”, “patients of African American heritage are not likely to benefit”, “patients with a history of suicide or suicidal tendencies etc are contraindicated”, it is difficult for us to reconcile a package insert that provides the proper benefit risk description of the reduced efficacy in North Americans patients.  That being said, we think the Advisory Committee is going to have a difficult time not requiring an additional study in US patients when the FDA asks them what further data should be collected.  It follows then that the FDA will not be able to issue an approval letter when the PDUFA Date rolls around on December 9, 2010.

GILENIA – PDUFA Date

The PDUFA Date for GILENIA (fingolimod) is September 21, 2010.  This Novartis drug for the treatment of multiple sclerosis was reviewed by the FDA’s Advisory Committee in June of this year and received an overwhelmingly positive endorsement.  There is little reason to believe that the FDA won’t be concurring with the Committee’s recommendation and approving this drug.

KRYSTEXXA – PDUFA Date

September 14, 2010 is the PDUFA Date that’s been set for Savient’s KRYSTEXXA (pegloticase) which has been submitted for the treatment of gout.  The BLA was resubmitted earlier this year after receiving a Complete Response Letter last summer which highlighted a number of manufacturing deficiencies.  The company met with the FDA and agreed on a way forward that resulted in the resubmission which addressed the manufacturing issues but also included a safety update from their clinical trial data base.  The company recently announced that it had submitted the final stability update on July 28, 2010.

It all looks good on paper.  There’s lots of articles out there providing the safety and efficacy data from a lot of the clinical trials.  The company has met with the FDA and provided a resubmission of the requested manufacturing information.  So, why doesn’t it feel good to us?  We don’t really know for sure but with all of the problems that we’ve seen with recalls for manufacturing related issues and the growing list of products that are in short supply because of these problems, it just follows that the FDA chemistry reviewers and the inspectors just might be spending their time elsewhere.  It is a close call but we wouldn’t be surprised to see a 3 month delay on this PDUFA Date to allow the FDA some breathing room.

AVASTIN – The next surprise?

On July 20, 2010, an FDA Advisory Committee will evaluate and discuss new data submitted by Roche for the use of Avastin in advanced breast cancer.  FDA granted Roche an accelerated approval under which Roche was to complete additional studies to confirm a survival benefit.  The FDA review indicates that these new studies don’t confirm the survival benefit seen in the first study.  This Advisory Committee debate should result in an NFC recommendation to the FDA.  Will the FDA allow the approval for advanced cancer to remain in the label?  We doubt it – the studies failed the regulatory hurdle established.  If they do, the indication will probably have significant limitations.  Regardless of the outcome of the Advisory Committee discussions and the final FDA action, the drug will still be available as it has multiple approved indications for use in the US.

QNEXA – Why the surprise?

Last week, an FDA Advisory Committee met to discuss QNEXA, the fixed dose combination drug from Vivus (VVUS) for the treatment of obesity.  While it is reported that there was Advisory Committee discussion that favored certain aspects of the drug, overall, the drug was not favorably considered by the committee.  The response to this NFC recommendation by the Advisory Committee was reflected in sharp drop in the share price in Vivus, down over 50%.  Does the drop in share price suggest that there were some investors actually expecting a positive recommendation by the Advisory Committee?  If so, we say why?  Did they think that a new fixed dose combination diet preparation could get out of the regulatory shadow cast by phen-fen?