Novo Confident of Victoza Victory at FDA in May

The odds might appear to be stacked against it, but Novo Nordisk sounds remarkably confident that GLP-1 analog liraglutide (Victoza) will get approval from FDA by the end of May.

OK, so it needs to be confident: even if it is approved as expected, the once-daily drug, already about four years behind schedule, will have barely a year to make its mark before Lilly/Amylin’s once-weekly version of the incumbent GLP-1 analog Byetta hits the market in 2010.

But Novo’s up against a very diabetes-resistant FDA, with strong memories of the Avandia fallout, that has recently changed its guidelines in this disease area to require more safety data among patients at high risk of cardiovascular disease. And this, as Novo’s CMO Mads Krogsgaard Thomsen acknowledges, is “just the reverse of how we’ve recruited patients into diabetes trials in the past,” including into the liraglutide Phase III trials.

Traditionally, companies have sought to prove their drug’s safety and efficacy in relatively clean patient populations first. Given the CV signal picked up from Avandia well after that drug was approved, it’s clear why the agency has taken a more severe stand.

Among the 6000 or so patients in the liraglutide Phase III trials, very few suffered CV-related events. That’s good for those 6000, but it’s less good as far as providing sufficient statistical power to convince an edgy FDA to wave the drug through. Worse still, since Victoza’s early April advisory committee meeting is widely expected to provide the test case for the new guidance, FDA will be keen to set examples, not make exceptions.

Still, Novo’s got its defense all lined up--and its fingers crossed. For one thing, argues Thomsen, the guidance relates only to drugs that were not submitted by the time it was published, late last year. (Novo submitted liraglutide in May 2008.) There's some controversy over this, but the guidance, as Thomsen underlines, specifically appears to refer to studies in the planning stage and studies completed before submission of the NDA/BLA. (See pages 3 & 4.)

Plus, he adds, "we did not a receive any letter from FDA to say we would have to adhere to the guidelines with liraglutide, as we did for our [Phase II, not-yet-filed] once-weekly GLP-1 analog NN9535." His second point: when looking at risk factors like body weight, systolic blood pressure or biomarkers of CV events, “our data shows nothing concerning at all,” Thomsen told The IN VIVO Blog.

Sure, but FDA could always retort with: “Nor did Avandia’s. That’s the point of our guidance.” At this stage, Novo is hoping that its willingness to do a post-approval study looking specifically at CV outcomes will be enough to win the agency’s favor. “Even though the event numbers are small, we’ve done the [CV event] analyses that the agency asked for--the same ones it will now require going forward--and this convinces us at least why there’s a good case for not requiring a pre-approval study.” He goes on to say that liraglutide may even provide CV benefits.

Favorable trends aren’t enough, though. But whatever hoops Novo has to jump through, its competitors, BMS/AZ and Takeda, both with DPP-IV inhibitors currently under review and, more pertinently, Lilly/Amylin with Byetta LAR, will have to do the same. And whether Novo has to do its CV outcomes trial before or after approval, at least that data will help it make its case in the next—likely even tougher—regulatory challenge it faces with liraglutide: getting it approved for obesity.

image from flickr user samthsham used under a creative commons license.