By Matthew Willett

Shadowed by carcinogencity study requests from the FDA that could delay development by up to 18 months, Pozen Inc. said its lead candidate for migraine, MT 100, met its final Phase III trial primary endpoints.

The Chapel Hill, N.C.-based company said the pain-relief formulation that combines a fast-release metoclopramide and an extended-release naproxen sodium proved more efficacious than either of its components individually.

Pozen CEO John Plachetka said the completion of clinical testing for MT 100 has produced a powerful regulatory package.

"MT 100 has performed at a very high level," Plachetka told BioWorld Today. "It's met or exceeded our expectations throughout the clinical trial program, and now we have a package of clinical trials we feel fulfills all the requirements the FDA had of this combination product."

The 2,500-patient study is the last of five Phase III studies. In other studies MT 100 demonstrated significant relief over placebo in pain and associated symptoms including nausea, light sensitivity and sound sensitivity.

Pozen's executive vice president of product development, Andrew Finn, told BioWorld Today the final Phase III results have held the compound to a higher standard than typical migraine investigations.

"In both [studies comparing MT 100 to its components] we've shown MT 100 to be superior to naproxen and metoclopramide," Finn said. "That was using an outcome measurement we've pioneered, one we call 'sustained relief.' It measures headache relief by two hours from administration and no recurrence over 22 hours, measuring an entire 24-hour period. That's a little different than the standard migraine outcome that just looks at whether it offers relief within two hours. We've taken a step forward, and it's a higher hurdle, but we think it's appropriate."

He added that the drug is as potent as Imitrex, GlaxoSmithKline plc's market-leading migraine therapeutic, without the cardiovascular risks triptans carry.

"We've shown it superior to its components in two studies in sustained relief, and also that its better than placebo in sustained relief," he said. "In one study the comparison group was Imitrex, and we showed a single tablet is as effective as Imitrex and two tablets produced a better response rate than Imitrex. From an efficacy perspective it's better than its components and better than placebo and at least as good as Imitrex."

Late last month Pozen saw its share price cut nearly in half - to $6.625 - on news that the FDA would require carcinogenicity studies related to MT 100. The company had requested a waiver that would have allowed it to file for approval without those tests. (See BioWorld Today, Jan. 29, 2001.)

Pozen's stock (NASDAQ:POZN) rose 68.75 cents Wednesday to close at $8.25.

Finn said discussions with the FDA on the design of carcinogenicity studies are ongoing. The studies could delay regulatory filing for the migraine therapeutic by as much as 18 months. He said the company would like to reach a middle ground with the FDA concerning the carcinogenicity studies.

"There are multiple options. It could be one study and no two-year study, or one study and a two-year study as a post-approval study," he said. "It could be a one-year study and another where we do a midpoint analysis. There are multiple iterations, and there's a lot of room between no study and a two-year study all before submission."

Pozen's most advanced drug aside from MT 100 is MT 300, an injectable dihydroergotamine mesylate compound for severe migraine pain, which is in Phase II testing. It should enter Phase III in the third quarter.

MT 400, a combination triptan and nonsteroidal anti-inflammatory, is in Phase II studies. Data are expected from that proof-of-concept study in the middle of this year, Finn said. MT 500, an in-licensed 5HT2b inhibitor, is slated to go into a Phase II proof-of-concept study later this year. n