Pozen Inc.'s injected migraine drug, MT300, achieved its primary endpoint - sustained relief of pain - in its second pivotal trial and, although the drug did not do as well meeting secondary endpoints during the two hours after dosing, it showed statistical significance in providing relief of those symptoms on a sustained basis.
And that's what matters most, said Andrew Finn, executive vice president of product development for Chapel Hill, N.C.-based Pozen.
"This is a point that the FDA has advocated - that we go beyond the two-hour time point," he said. "If you look at [sustained relief] for pain, why not look at it for the secondary symptoms, as well?"
Other researchers "haven't looked at the secondary symptoms this way at all, and it's very early for other companies to be looking at pain in sustained response," he added.
The second Phase III study, like the first, compared MT300, which is a new formulation of dihydroergotamine targeting various serotonin receptors, to placebo in 550 acute-migraine patients. (In all, 610 were dosed, but data from patients at one site had to be discarded because protocol was not followed.)
Sustained relief was the primary endpoint, defined as relief within two hours of dosing and no relapse or re-use of medicine during the next 22 hours. In this regard, MT300 did better than placebo: 34 percent as compared with 21 percent. For pain relief at two hours, the numbers for the drug and placebo were 48 percent and 36 percent, respectively.
Secondary endpoints measured nausea and sensitivity to light and sound. Here, MT 300 was not statistically superior to placebo over the two-hour, post-dose period. But a statistically significant greater number of patients treated with MT 300 did get sustained relief in those categories as well.
"We hit on two of three and just barely missed the third," Finn said.
In sensitivity to light, 26 percent of drug patients got sustained relief compared to 17 percent on placebo. In sensitivity to sound, the numbers were 33 percent vs. 24 percent. The difference between MT 300 and placebo in the sustained relief of nausea was 36 percent vs. 29 percent (p=0.075).
As for adverse events, injection site reaction was the most common, showing up in 30 percent of drug subjects and 22 percent of placebo. Other adverse events included dizziness (5 percent with drug vs. 3 percent with placebo), diarrhea (4 percent vs. 1 percent), nausea (3 percent vs. 1 percent), abdominal pain (3 percent vs. less than 1 percent), and limb pain (3 percent vs. less than 1 percent).
In July, the first pivotal Phase III study of MT300, dosing 619 patients, showed the sustained response was statistically significant compared to the rate for placebo - 37 percent vs. 19 percent (p<0.001). The drug also provided quicker relief to patients, helping more migraine sufferers at two and four hours after dosing, and gave statistically significant relief vs. placebo in the secondary endpoint measurements. (See BioWorld Today, July 23, 2002.)
Pozen expects to file a new drug application by the end of this year, and MT300 could be on the market by the end of next year, said Matt Czajkowski, chief financial officer of the company. The data are "complete, as far as we're concerned," he said.
MT300 would compete with two others in the migraine space, most notably London-based GlaxoSmithKline plc's Imitrex (sumatriptan succinate), which is selling about $200 million annually.
Another treatment is Basel, Switzerland-based Novartis AG's injected DHE-45 (dihydroergotamine mesylate), also sold in an inhalable version called Migranal. Finn said MT300 represents an improvement over both.
"The advantage we think we have over Imitrex is a much cleaner cardiovascular profile," Finn said. Compared to DHE-45, MT300 causes less nausea. Also, it's "in a pre-filled syringe, rather than a glass ampule that must be broken open" and the medicine withdrawn from - all while the patient is in the throes of the migraine, he noted.
Injectable drugs in general are less preferred by patients than oral treatments, of course, and Pozen has two oral treatments for migraine in late-stage development: MT100, for which Phase III studies have been completed and rat carcinogenicity data are being prepared, with the company planning to file a new drug application in the first half of next year; and MT400, for which Phase III trials are expected to begin in the first quarter of next year.
Czajkowski said that "currently, those are the only active clinical trials we're conducting, but we are looking at a range of other potential products that would be beyond the migraine area," such as pain and central nervous system disorders.
Pozen's stock (NASDAQ:POZN) rose 18 cents Friday to close at $5.10.