FDA and Drug Safety: It Keeps Getting Worse

How bad is the drug safety climate? Just ask GlaxoSmithKline.

Sure, last Monday was a rough day—nothing like having two FDA officials tell an advisory committee that one of your biggest products ought to be pulled—but we’re not talking about Avandia today.

No, today we are talking about the product formerly known as Trexima, a fixed-dose combination of the GSK’s migraine drug sumatriptan (Imitrex) and the nonsteroidal anti-inflammatory drug naproxen. GSK is developing the combo in partnership with Pozen. On July 31, the Food & Drug Administration issued a second “approvable” letter for Trexima, saying that it is still not convinced the combination is safe enough for marketing. (FDA has already told the companies that it will not approve the Trexima brand name, but the firms are still using it until they settle on a new one.)

In particular, Pozen says, FDA is concerned about a positive genotoxicity test. The agency apparently wants the company to conduct a relatively simple human study to provide reassurance that it is a false signal. This comes after FDA previously declined to approve Trexima because of concerns about the cardiovascular safety profile of the combination.

Keep in mind that this pill combines two ingredients that have been used together countless times in the 15 years that Imitrex has been on the market. If there really is a safety problem here, FDA probably should be doing more than just sending an “approvable” letter to Pozen.

To be fair, Imitrex has well known cardiovascular risks, and naproxen’s cardiovascular safety profile became an issue in the context of the cox-2 inhibitor safety brouhaha. So you can understand why FDA asked for more data. Now, Pozen says, the agency is satisfied on that front (thanks in part to GSK’s willingness to do a post-marketing study on the blood pressure effects of the combo). But the drug is still on hold.

Welcome to the world of new drug reviews in 2007. Trexima is just the latest indication that this may be the worst time ever to try to get a new drug through FDA.

There should be good news soon. Congress is on the verge of enacting historic drug safety legislation—at least, Congress says it will after August vacation. The bill will put new burdens on manufacturers to be sure, but it will also allow Congress to declare the drug safety problem to be fixed. That may lead to increased confidence in FDA as a regulator—and maybe increased confidence within FDA itself to allow the agency to approve drugs even if they do have a safety signal.

SHAMELESS SELF-PROMOTION ALERT: The RPM Report and Ropes & Gray will host a webinar on Aug. 14 to discuss the impact of the pending FDA bill. Two experts from Ropes & Gray’s legal practice will dissect the key provisions of the legislation, and the editors of The RPM Report will tease out the business implications of the law. Registration information is available here.