Archive for December 2010

CONTRAVE – post Advisory Committee, pre-PDUFA Date

We are post FDA Advisory Committee for the CONTRAVE (OREX) application which is seeking approval for use in the treatment of obesity but we are still awaiting the decision that counts – the action of the FDA on the application.

Many of us are still trying to come to grips with the Advisory Committee vote which recommended approval for this drug. It had only marginally better efficacy data than the other obesity drugs that were presented to this committee earlier this year but still had some cardiovascular problems and other safety issues that seem to tilt the benefit risk meter to the “too much risk” side. When you take into consideration that one of the alternative treatments is diet and exercise, the benefit risk meter goes off the scale with the risk clearly “outweighing” the benefit. Granted, obesity is a problem but is approving this fixed drug combination the solution? The data clearly show that this fixed combination of naltrexone and bupropion is not the magic bullet for clinically meaningful weight loss – it has side effects.

The bottom line is that there is still no reason to believe this fixed combination will gain approval. If the medical community believes there is merit in this combination, they are free to prescribe it as both drugs are available as generic single entity products.

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.

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.

CONTRAVE – Advisory Committee Meeting

On Dec 7, 2010, Orexigen Therapeutics (OREX) will present the data on CONTRAVE to an FDA Advisory Committee seeking its recommendation for use of CONTRAVE  (bupropion SR/naltrexone SR) in the treatment of obesity.

Some may think that a positive recommendation for a diet drug is overdue from this Committee because they have already failed to recommend approval for two other diet drugs just this year.  Those who think that way are mistaken.  We think this Advisory Committee is tuned in to the same wave length as the FDA on these drugs. They will see this as another fixed combination diet drug and look for a positive benefit risk ratio. We don’t think they’ll find one.

ZICTIFA – Advisory Committee Meeting

On December 2, 2010, Astra Zeneca will present data to the FDA Oncology Advisory Committee for ZICTIFA (vandetanib) hoping to get their recommendation for the treatment of unrestable (non-operable) locally advanced or metastatic medullary thyroid cancer.

This should be an interesting discussion to watch – a study of contrasts.  While the disease is not one of the most serious cancers, the clinical trial data show a more than 50% increase in survival time BUT with a 31% incidence of serious adverse experiences compared to only 13% for placebo.  So, the balance of a significant improvement in survival will be compared with a significant incidence of serious adverse experiences will be discussed.  How does FDA feel about this?  They appear to be leaning towards approval of this drug but with some caveats.  They are asking the Committee to discuss 2 options that will help improve the benefit risk ratio.  The first is restricting the labeling to a more serious patient population than AZ is seeking.  The FDA is asking the Committee to limit use to patients with progressive, symptomatic medullary thyroid cancer.  The second option is for the Committee to discuss the evaluation of lower doses in a post-marketing study.

If AZN can provide the sub group analyses that show similar improvement in these more serious patients and also provide data showing a reduction in the incidence of the serious adverse events in patients who had their dose adjusted downward, the Committee might be just inclined to give their recommendation for approval in this limited population with more specific instructions on dosing.