Vivus vs. the FDA: Round Two

In an earlier post, I promised to provide updates about the on-going saga to get an obesity drug approved by the FDA and surprisingly, there is some news on that front from Vivus.

Despite the FDA’s rejection of Qnexa back in October of last year, Vivus has decided to go for broke and give it another try.  If you recall, Qnexa is a combination of phentermine and toperimate, two drugs that are already FDA-approved.  The problem is that mothers who take toperimate during pregancy may have a greater risk of delivering a child with a cleft palate.  Due to the anticipated widespread use of any approved obesity drug (including use by pregnant women), the FDA has set very high standards in terms of safety (some would say ridiculously high standards).  Needless to say, an obesity drug that causes birth defects would not meet those standards.

In their latest press release, Vivus announced that the FDA has accepted an early resubmission of their NDA based on three recently completed studies…

“Topiramate teratogencity data published and presented since our last meeting with the FDA in April 2011 includes two case-control studies….In addition, a birth defect study from Denmark on newer generation antiepileptic drugs including topiramate was published in JAMA. In all of these studies, the authors concluded that topiramate was not a major teratogen,” commented Wesley Day, vice-president clinical development.”

I wish Vivus all the best, but I’m a little concerned about this resubmission.  First off, the quote “the authors concluded that topiramate was not a major teratogen” (the emphasis is mine) doesn’t exactly instill confidence in terms of the drug’s safety for pregnant women and the children they are carrying.  However, it appears that Vivus will be pursuing an indication that excludes pregnant women, at least for the initial NDA…

“In this initial indication, we plan to include a contraindication for women of childbearing potential. We believe this is a sound approach that, if approved, will potentially allow early commercialization in a higher-risk population with a significant unmet medical need.  The FORTRESS study remains important in our plan to more precisely define the teratogenic potential of topiramate and may enable us to expand the indication to include obese women of child-bearing potential.  If the FORTRESS results are favorable, we expect to file for the full indication in late 2012.”

You might be thinking “What’s the problem? They just won’t give it to pregnant women!”

Well, the issue is two-fold:

1. Vivus included a contra-indication for pregnant women with their initial NDA and it was rejected.  You can say that pregnant women shouldn’t take Qnexa, but it’s difficult to convince the FDA that they won’t.  Unless Vivus can institute a very rigid REMS program to ensure that pregnant women won’t have access to the drug, I feel that the FDA is not going to play along.  Since the FORTRESS study results are expected in late 2012, and I assume that it is a very comprehensive study of the teratogenicity of toperimate, the FDA may say “Still too risky, let’s just wait until the FORTRESS date comes in.”
2. If Vivus does offer an acceptably rigorous REMS program to keep pregnant women from getting access to Qnexa, it will severely curtail the launch of the drug.  A rigid enough REMS program will likely mean that only certain doctors can prescribe Qnexa, only certain pharmacies can fill these prescriptions and for each patient who takes the drug, an extensive tracking system will have to instituted to collect all the follow-up safety data.  Not exactly conducive to big revenues, now is it?

However, the FDA did agree to the early resubmission, so I assume that the agency sees some validity to Vivus’ data and amended NDA.  This story will definitely be worth keeping an eye on and if Vivus is successful, it may pay off handsomely for them, but I feel that they still have a long road ahead of them.