Posts tagged ‘PDUFA Date’

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.

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.

PDUFA Date – STACCATO loxapine

October 11, 2010 is the PDUFA Date for Alexza Pharmaceuticals STACCATO loxapine, an inhalation formulation of loxapine intended for rapid treatment of schizophrenia and bipolar disorders.  The company reports that this is the first NDA that it has submitted using the STACCATO inhalation technology.  Phase III clinical studies are reported as having been submitted that support both indications but few details are available other than reports that both primary and secondary endpoints were met.  Getting approval for both indications using new technology seems like a bit of a hurdle for a company that is submitting its first NDA.

DYLOJECT – PDUFA Date

October 3, 2010 is the scheduled PDUFA Date for Javelin Pharmaceuticals DYLOJECT for the management of post operative pain.  The company has been silent on any actions that may have been taking place with the FDA on this submission.  One possible source of a delay on the approval of this application could be gaining assurance that the problems that led to the withdrawal of the product in the UK earlier this year are not potential problems in the US.

ZALBIN – PDUFA Date

October 4, 2010 is the PDUFA Date for the Human Genome Sciences product ZALBIN for hepititis C.  We’ve not seen anything since the company announced that it had received a Discipline Review letter from the FDA on June 6, 2010.  The FDA cited Benefit/Risk issues for the dosing regimen.  The company indicated at that time that they thought licensure was unlikely.

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.