pain is not necessarily
The U.S. Food and Drug Administration
that cropped up in rats. Both of these
so they don't tell us much about how regulators are feeling about Vivus' weight-loss drug Qnexa.
Investors don't have to wait too much longer, however, since FDA is expected to make an approval decision about Qnexa on Thursday.
The big question is not whether or not FDA rejects Qnexa Thursday -- the agency almost certainly will issue a complete response letter based on the
. More important is what's inside the complete response letter. What sort of "path forward" -- to use Arena's terminology -- does the FDA lay down for Vivus?
To make sure I didn't miss any of the possible outcomes for Vivus Thursday, I turned to JMP Securities analyst Jason Butler for some help:
Let's start quickly with the best possible outcome even though it's not likely to happen: FDA grants full approval to Qnexa. Again, don't expect this to happen.
On the total flip side, the absolute worst possible outcome, also unlikely: The FDA tells Vivus that Qnexa can never be approved because the drug poses too great of a risk to women who may get pregnant while using Qnexa. More on Qnexa's birth-defect risk later.
Another potential, really bad outcome but one not to be dismissed entirely: The FDA asks for a
cardiovascular outcomes study to rule out the possibility that Qnexa raises the risk of heart attacks and strokes. Recall in the phase III studies, Qnexa was associated with a small increase in heart rate that Vivus insisted was benign but FDA and panel members highlighted as a potential risk.
A pre-approval Qnexa heart safety study would be very expensive and take years to complete. It would also decimate Vivus' stock price because few, if any, investors, would have the patience to wait out that kind of delay.
The likelihood is this nasty scenario coming to pass is low. In the wake of the Avandia and Meridia drug safety controversies, FDA could have easily established a policy requiring pre-approval cardiovascular outcomes studies for all new obesity drugs. The FDA, based on Arena's complete response letter, has not done that.
Here are some demands and concerns more likely to make an appearance in the FDA's complete response letter for Qnexa:
A requirement for a
cardiovascular outcomes study: Entirely possible, if not probable, but okay even positive for Vivus as long as reaching agreement with FDA on a trial design doesn't drag on forever.
Qnexa's pregnancy risk: Topiramate and phentermine, the active ingredients in Qnexa, are both approved and well-understood drugs from a safety standpoint. A possible link between topiramate and birth defects has been previously identified and the drug already carries a warning to pregnant women in its label. No birth defects were recorded in the Qnexa trial but that didn't stop FDA panel members from raising alarm bells.
Best case for Vivus would be an agreement that Qnexa carry a "Category X" warning on its label, restricting pregnant women or women planning on getting pregnant from taking the drug to lose weight. The FDA may also ask for more data to make sure that Qnexa doesn't cause birth defects if used by a woman who becomes pregnant while taking the drug.
Vivus wins if FDA allows the company to collect this data after Qnexa's approval through some type of pregnancy registry. Vivus blows up if FDA asks for pregnancy risk data prior to approval.
The absence of long-term Qnexa safety data: FDA may want to see two year's worth of safety data, which Vivus can submit relatively quickly since the
. Obviously, if FDA asks for a new clinical trial, Vivus is in serious trouble.
Negotiation of a risk-management plan: It's all but guaranteed that FDA will place Qnexa under some type of restrictive risk-management plan. Ordinarily, that might be a downer for Vivus, but not when you consider that simply getting an obesity drug approved would represent a major victory.
It's impossible to estimate how long it will take for Vivus to respond to an FDA complete response letter until we know what the agency wants. If we cross our fingers and assume the best -- post-approval cardiovascular outcomes and pregnancy registries, no pre-approval clinical trials, negotiations on a risk-management plan and drug label -- Vivus could probably resubmit Qnexa in the first half of 2011. That would suggest a second shot at approval toward the end of 2011.
Given that Arena is looking at a two-year delay with its weight-loss drug, Vivus and its investors will gladly take a one-year pushback for Qnexa.
--Written by Adam Feuerstein in Boston.
>To contact the writer of this article, click here:
>To follow the writer on Twitter, go to
>To submit a news tip, send an email to:
Adam Feuerstein writes regularly for TheStreet.com. In keeping with TSC's editorial policy, he doesn't own or short individual stocks, although he owns stock in TheStreet.com. He also doesn't invest in hedge funds or other private investment partnerships. Feuerstein appreciates your feedback;
to send him an email.