Friday, September 05, 2008

Whoa Nelly: FDA Puts the Brakes on Liraglutide

When FDA knows six months ahead of a user fee deadline that it won’t be able to make an on-time approval decision, it’s not exactly a positive sign of a drug’s future prospects.

But that is exactly what Novo-Nordisk is facing with its once-daily human GLP-1 analogue liraglutide—the company’s much anticipated type 2 diabetes therapy.

FDA isn’t scheduled to make a decision on the approvability of liraglutide until March 23 at the earliest. But despite being six months away from the user fee deadline, the agency has already warned the company not to expect an on-time approval.

The delay, Novo says, will allow time for FDA to absorb feedback from an advisory committee review of liraglutide, which has been scheduled for March 2. The agency told Novo that it doesn’t believe the three weeks between the meeting and the user fee deadline will be enough time to complete the review.

“Since the advisory committee meeting is held shortly before...[the user fee] date, the agency has indicated that it will most likely have to extend the date of completing their assessment by a couple of months,” Novo said in a press release.

While FDA has certainly been able to deliver approvability decisions within three weeks of an advisory committee meeting in the past, there are two reasons why it is different this time around for liraglutide.

First, the agency is simply missing more user fee deadlines—something that we’ve been tracking and writing about in The RPM Report. While FDA is allowed to miss approval deadlines under the Prescription Drug Fee User Act, drug reviewers were given a green light to start missing more than usual earlier this year.

Based on some pretty small numbers, we've found that the longer a drug sits at FDA, the less of a chance of a positive decision. So if the agency is indeed just a "couple of months" late on liraglutide, that seems to bode well for the drug's approvability prospects. That is, of course, barring any other unforeseen (or seen) circumstances.

Which brings us to our second point. FDA is obviously taking it a bit slow on liraglutide given the pancreatitis safety signal seen with another GLP-1: Amylin’s exenatide (Byetta). Novo’s challenge at what will surely be a closely watched advisory committee meeting will be to make a convincing case that its product does not carry the same signal as Byetta.

As the Diabetic Investor points out, we’ve already seen this play out in the diabetes market over the cardiovascular safety issues with GlaxoSmithKline’s rosiglitazone (Avandia). As Avandia was imploding, Lilly/Takeda were asked to defend the safety profile of their thiazolidinedione drug product, pioglitazone (Actos). And in that case, they succeeded.

1 comment:

Fred Cohen said...

Your readers might be interested in a freely available comprehensive report I wrote a couple of years ago summarizing recent FDA experience reviewing NDS/BLAs, focusing on delays in approval for drugs eventually approved (i.e. "approvable" decisions).

The SSRN download is liked from my consulting website's library at

Fred Cohen