Posts tagged ‘BENLYSTA’

BENLYSTA – PDUFA Date

Last month, the FDA Advisory Committee recommended approval for the HGSI/GSK drug BENLYSTA for the treatment of lupus, the first new treatment for lupus to come down the road in decades. We pointed out the difficulties the FDA would have with conveying the safety and efficacy information into a meaningful package insert.  The Committee either looked beyond that or thought the regulatory obstacles facing the FDA as they try to write the package insert could be easily overcome.  While we provided some wording suggestions at the time, we don’t think the FDA can resolve this issue in a timely manner, certainly not before the PDUFA Date of December 9, 2010 unless HGS and GSK both want this approval so badly that they roll over with a very restrictive package insert.

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.