Posts tagged ‘Glaxo Smith Kline’

FDA Advisory Committee – LAMICTAL XR

On March 10, 2011 the FDA will ask the Peripheral and Central Nervous System Drugs Advisory Committee to vote on the use of GlaxoSmithKline LAMICTAL-XR as monotherapy for partial seizures.  Listed on the undercard of the main event, is a discussion and series of questions that the FDA wants the Committee to address related to the use of historical controls.
The first question that the FDA is asking is whether it is ethically acceptable to conduct placebo-controlled studies in this patient population.  To me, the answer is as obvious as if the question was asked by any FDA Division of any Advisory Committee about any disease that has FDA approved drugs available to treat the disease.  That answer is NO.
However, I don’t understand the rest of it.  And, by the “rest of it” I mean the questions and the development strategy that led to the questions.  LAMICTAL is approved as an immediate release product as monotherapy for the treatment of partial seizures.  Why wasn’t it sufficient to do a bioequivalence study with some clinical parameters?  I understand that a “non-inferiority” trial might have been prohibitively large but the difficulties listed by the FDA with the French et al approach is like scoring a heavy weight title fight by who had the fewer missed punches.
That being said, it would appear that the FDA review is relatively positive with the conclusion being that the data are adequate for approval.  Let’s hope the Committee doesn’t get confused with all missed punches and can focus on the fact that all this is about is an extended release formulation of a drug that is already approved for the indication as an immediate release product.


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.

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 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.


  • 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.