Pozen Inc. began the final Phase III pivotal trial of MT 300 for treatment of severe migraine, with the goal of filing a new drug application by year’s end.
Pozen, of Chapel Hill, N.C., now has two Phase III trials under way for MT 300, an injectable dihydroergotamine mesylate compound. The trial just launched is a double-blind, placebo-controlled study that will include 400 patients who suffer from acute migraine. The primary endpoint is sustained pain response, with nausea and sensitivity to light as secondary endpoints.
Separately, CEO John Plachetka said the company plans to request that the FDA allow Pozen permission to submit an NDA this year for its lead compound, MT 100, which the FDA stymied a year ago when it required that additional carcinogenicity studies be completed prior to approval. MT 100 is a proprietary formulation of two drugs already approved, a fast-release metoclopramide and naproxen sodium. Pozen had just completed an initial public offering in November 2000, and upon the news from the FDA, its stock fell 49 percent. (See BioWorld Today, Jan. 29, 2001, and Feb. 22, 2001.)
Last week, Pozen announced preliminary results from its first transgenic p53 mice carcinogenicity study in response to the FDA’s request for two additional rat studies, and Plachetka said the study indicated that MT 100 was not carcinogenic. He said the company has checked for genetic and chromosomal damage, and he said MT 100 causes neither.
The final results of the ongoing carcinogenicity study in rat will be available in 2003, he said, noting that the company needs the FDA’s permission to go forward.
“They obviously have some concerns, and from their position have a valid reason for asking us to do this work,” Plachetka said. “We never disagreed with them in a way that would reflect on their decision.”
Until then, Pozen will continue its work on MT 300, which is a new formulation.
“We changed the formulation in Phase I before we gave our drug to humans, including the pharmacokinetics and absorption,” Plachetka said. “The result is far less incidence of nausea than the old formula.”
Plachetka said the company determined in Phase II trials that the peak blood level is not what determines the efficacy, but does influence the nausea. The new formulation has a much lower peak blood level, which has improved the efficacy while limiting the side effects. Also, the Phase II trial demonstrated a less than 20 percent relapse rate.
This Phase III trial is expected to conclude during the second quarter, with data available in the third quarter.
Pozen is continuing its work on a another Phase III trial for MT 300, which involves 600 patients at 30 U.S. centers. It is scheduled for completion this quarter, with data expected to be available in the second quarter.
Pozen also has MT 400, a combination triptan and nonsteroidal anti-inflammatory, about to go into a dose-ranging Phase II trial. The company has completed a proof of concept and has two patents for this combination therapy.
Another compound, MT 500, a 5HT2b inhibitor, is at the end of its first Phase I trial.
Pozen’s stock (NASDAQ:POZN) gained 63 cents, or about 10.5 percent, to close at $6.64 on Thursday, when Pozen announced the new Phase III trial. On Friday, it fell 17 cents to close at $6.47.