Once again, the FDA has delayed approval for the widely anticipated Eliquis bloodthinner. In a move that surprised investors, the agency issued a so-called complete response letter to Pfizer and Bristol-Myers Squibb, which hoped to begin marketing this summer and, eventually, generate billions in dollars of annual sales. The FDA, though, wants what the drugmakers are calling "data management and verification" from a key clinical trial, but no new studies (read here).
Eliquis, which is designed to prevent strokes and clots in patients with atrial fibrillation, has been envisioned as the potential leader of three new blood clot treatments meant to replace warfarin - the longstanding oral standard of care for the condition. The other new bloodthinners are Xarelto, which is sold by Johnson & Johnson and Bayer, was approved last November for treating atrial fibrillation and Pradaxa, which is sold by Boehringer Ingelheim, but has been plagued by side effect reports (see this).
This marks the second time, however, in recent months that Eliquis approval has been delayed. Last year, Phase III results showed that Eliquis prevented more strokes with less major bleeding than warfarin, the decades-old standard treatment in patients with atrial fibrillation, and also reduced the number of deaths. And so last November, the FDA decided to give Eliquis a priority review and the so-called PDUFA, or FDA approval date, was set for last March (look here).
But that was pushed back until this month amid speculation that the FDA may hold an advisory committee to review the drug, although that did not pan out (see this). Now, though, this latest delay is causing confusion, although one Wall Street analyst maintains the bloodthinner is still viewed as the best among the newest treatments.
"If there is any material controversy in the data, going up before an FDA advisory committee is still a possibility, but at present, this is difficult to handicap," writes Sanford Bernstein analyst Tim Anderson in an investor note, adding that it is unclear what questions the FDA has for the drugmakers. "All of this is surprising given the widespread perception that Eliquis is a best-in-class product relative to" Pradaxa and Xarelto.
For the moment, this is a boost, of course, to the other drugmakers. J&J and Bayer, for instance, last month suffered their own setback when an FDA advisory panel voted 6-to-4 – with one abstention – against recommending Xarelto for treating patients with acute coronary syndrome. But when might Eliquis win approval? Anderson writes that late 2012 is plausible, but this remains uncertain, depending upon whether the drugmakers are able to quickly satisfy the FDA.
Neither drugmaker is "willing to give a timeline for re-submission at this point. However, our belief is that the issues raised in the letter are unlikely (but this is certainly not assured) to alter the overriding conclusions that Eliquis is superior to warfarin on both bleeding and efficacy (stroke prevention)," ISI Group Mark Schoenebaum writes in an investor note. "If we are correct, then, although this is a material time delay, we don’t see an impact to our conclusion that Eliquis will eventually dominate the blood thinner space.
"In our opinion, the phrase 'data management and verification' means that, in selected cases, FDA likely wants assurances that strokes and bleeding episodes as described in BMY/PFE’s data sets are accurate. This might require the companies to request actual patient records from certain sites and could require the aid of a CRO (contract research organization). It is not clear yet whether these issues are widespread or limited to, say, a selected number of clinical sites," he continues, adding that approval may occur by mid-2013, at the latest.
alarm clock pic thx to alancleaver on flickr