Daiichi Sankyo's campaign to win approval for its atrial fibrillation drug edoxaban gained some support from regulators at the FDA who were clearly won over by the efficacy data in the NDA. But the internal review of the drug also includes recommendations for limiting its use to patients with abnormal kidney function. And they include a few cautionary notes on the competing drugs that have already made it to the market.
The lengthy FDA review, which was posted online ahead of Thursday's advisory committee meeting, concludes that Daiichi Sankyo ran a large and well designed study for edoxaban, coming up with data that supports its 60 mg dose. A 90 mg dose, they added, would raise concerns of excess bleeding. But analysts in this field have been impressed by the drug's overall safety profile.
After reviewing a few options, the regulators noted, "we are currently recommending the second option, approval of edoxaban 60 mg QD in patients with NVAF, with a limitation of use to patients with abnormal renal function (< 80 mL/min). We hope that another trial perhaps using a dose titration stategy to achieve a higher exposure level (on par with the exposure in the mild renal insufficiency subgroup) will be conducted in subjects with normal renal function. After considering the advice from the Cardiovascular Advisory Committee which will convene at the end of October, 2014, we may revise our recommendation."
One problem with edoxaban, they note, is that there are several similar therapies already on the market, including two which proved superior to warfarin--something edoxaban failed to accomplish. But…
"It is obvious to question whether edoxaban could be inferior to other approved therapies and whether this constitutes a reason not to approve," states the review. "Because edoxaban came close to achieving superiority on its primary endpoint it is not reasonable to conclude that edoxaban is inferior to dabigatran or apixaban in the overall NVAF patient population. Therefore, an approval on the basis of the overall trial results would not be inconsistent with the 1995 Shultz Federal Register notice."
The review gives Daiichi Sankyo good cause to be excited about a likely vote in its favor later in the week and an approval at the agency. But it may well need more studies to help broaden its use and refine its argument with payers.
Once on the market edoxaban would compete with Xarelto from Johnson & Johnson ($JNJ) and Bayer, Bristol-Myers Squibb ($BMY) and Pfizer's ($PFE) Eliquis, and Boehringer Ingelheim's Pradaxa, in addition to the much less expensive warfarin.
- here's the FDA's review