The potential for vascular risk with Endo Pharmaceuticals' Frova (frovatriptan succinate) 2.5 mg tablets could derail the company's sNDA for short-term prevention of menstrual migraine, which was deemed "not approvable" by FDA.

The company announced Oct. 1 that the agency had "identified deficiencies and asked for additional information pertaining to" the application.

FDA noted in the not approvable letter that "even though serious vascular adverse events were not observed in this drug development program, an increased risk (compared to the approved acute use) could not be ruled out," Endo said in a news release.

In addition, "while the FDA acknowledged that both pivotal efficacy trials that had been submitted as part of this sNDA met their primary endpoints in significantly improving the number of headache-free perimenstrual periods (PMPs), it questioned whether the benefit demonstrated was clinically meaningful."

Chadds Ford, Pa.-based Endo and its British partner Vernalis are seeking to be the first to secure FDA approval of a triptan for the menstrual migraine indication.

The sNDA was supported by a 427-patient Phase III study, which met its primary endpoint of number of migraine-free perimenstrual periods as well as secondary endpoints including reduction in headache intensity and reduction in rescue medication use. No serious adverse events were reported.

"We believe that the data submitted to the FDA was sufficiently compelling to warrant approval," Endo CEO Peter Lankau stated.

"Despite this, the FDA raised a number of issues that will need to be fully analyzed and then discussed with the FDA. Following this discussion with the FDA, Endo and Vernalis will decide upon the appropriate course of action."

The action date for the sNDA was twice delayed, more recently to Sept. 30 from Aug. 19 to give FDA more time to review the claim but the agency did not request any additional information or clinical trial data (¹ Also see "Frova Menstrual Migraine Claim Gets Extension" - Pink Sheet, 10 September, 2007.).

The sNDA originally had an action date of May 19, but the firms announced in March that the agency would complete the review instead by Aug. 19.

Frova has been approved since 2001 for the acute treatment of migraine attacks with or without aura in adults where a clear diagnosis of migraine has been established.

- Brooke McManus (b.mcmanus@elsevier.com)

FDA “Not Approvable” Letter Questions Benefit Of Endo’s Frova In Menstrual Migraine

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