Archive for March 2011

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!!

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.

Novartis Advisory Committee Meeting – indacaterol

On Tuesday, March 8, 2011, the Pulmonary-Allergy Drugs Advisory Committee will meet to discuss Novartis‘ NDA for indacaterol in the treatment of COPD.

This trip before the AdComm is one of the last steps in a long journey Novartis has had with this drug in the US.  They originally submitted the NDA for both a 150 mcg and 300 mcg once a day dosing regimen in COPD.  The FDA didn’t like the application for several reasons:

  • all other COPD treatments offer only one dose, not a choice
  • the 300 mcg dose seemed to present some safety issues without an apparent efficacy advantage.

Novartis and the FDA agreed to a program that studied a lower dose, 75 mcg once a day.
The results are in and guess what?  The FDA still doesn’t like the application for several reasons:

  • all other COPD treatments offer only one dose, not a choice
  • the 150 mcg dose seems to present some safety issues without an apparent efficacy advantage.

Looking at the efficacy data that the FDA has highlighted in their Briefing Document, it’s hard to disagree with them.  There is a very modest improvement with the 150 mcg dose over the 75 mcg dose.  The safety issues that the FDA raises are real in the mind of the FDA reviewer, therefore, they are real!

The questions posed to the Advisory Committee members come down to the same basic rationale that has guided the FDA recently:

  • Is the drug efficacious?  yes
  • Is the drug safe?  yes
  • Is the benefit risk on the positive side of neutral?  Here is where the problem is.  The FDA is saying that their perception of benefit risk is that both appear to be positive but 75 mcg is better than 150 mcg, so why do you need 150 mcg?
  • Can adequate labeling be written to guide the medical community?  Here’s the other problem for FDA.  It doesn’t see the need to give a choice of 2 doses because you probably can’t write a package insert intelligently enough to help the medical community make the decision between the two.

The questions to the Advisory Committee appear easy to answer except the dreaded c) “If not, what further data should be obtained?”

I suspect the Advisory Committee will see where the FDA is going with this and recommend approval of the 75 mcg once a day and take the 150 mcg dose off the table.  Hopefully, Novartis won’t argue to strongly for 150 mcg and take the approval.