Alexza Announces Preliminary Results from its AZ-104 (Staccato(R) Loxapine) Phase 2b Trial in Patients with Migraine Headache
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MOUNTAIN VIEW, Calif., Sept. 14 /PRNewswire-FirstCall/ -- Alexza Pharmaceuticals, Inc. (Nasdaq: ALXA) today announced preliminary results from its 366 patient Phase 2b clinical trial of AZ-104 (Staccato(R) loxapine) in patients with migraine headache. Both AZ-104 dose groups trended towards statistical significance, but the study did not meet its primary endpoint, which was defined as pain-relief at the 2-hour time point, compared to placebo. There were no serious adverse events in the clinical trial, and AZ-104 was generally safe and well tolerated in this patient population.

"The failure to reach statistical significance on the primary endpoint is disappointing, as we were not able to reproduce the positive clinical findings from our AZ-104 Phase 2a proof-of-concept clinical trial," said James V. Cassella, PhD, Senior Vice President, Research and Development at Alexza. "Loxapine is a drug that had not been previously studied in migraine patients, except for our earlier proof-of-concept study. As part of our collaboration with Symphony Allegro, we initiated this migraine program in 2007 to investigate whether loxapine might be a viable product candidate for migraine, due to the scientific rationale that loxapine's primary mechanism of action (dopamine antagonism) has shown effectiveness in treating migraine."

"We continue to be impressed with Staccato's ability to safely and very accurately deliver a portfolio of drugs in a simple, one-breath, patient-controlled inhalation," said Thomas B. King, President and CEO of Alexza. "The uniqueness of our Staccato technology allows us to examine medicines for both known and new indications, and we will continue to do so in a patient setting. Not every clinical trial will necessarily have positive findings. However, there is much value we can bring to patients through our Staccato technology, as evidenced by our late-stage, pre-NDA program with AZ-004 (Staccato loxapine, high dose) for the acute treatment of agitation."

AZ-104 Phase 2b Clinical Trial Design

The AZ-104 Phase 2b clinical trial was an outpatient, multi-center, randomized, double-blind, single administration, placebo-controlled study. The study was designed to evaluate the treatment of a single migraine attack of moderate to severe intensity in each of approximately 360 migraine patients, with or without aura. Two doses of AZ-104 (1.25 mg and 2.5 mg) and placebo were evaluated in the clinical trial. The study enrolled a total of 366 patients: 125 patients in the placebo dose group, 121 patients in the 1.25 mg dose group, and 120 patients in the 2.5 mg dose group.

Patients rated their headache pain using the International Headache Society (IHS) 4-point rating scale. The primary efficacy endpoint was headache pain relief (headache pain rated as mild or none) at 2 hours post-dose. Secondary efficacy endpoints for the clinical trial included various additional measurements of pain relief, as well as effects on nausea, vomiting, phonophobia and photophobia. All results were considered statistically significant at the p < 0.05 level, as compared to placebo, and all analyses were made on an intent-to-treat basis. Safety evaluations were also made throughout the clinical trial period.

Primary Efficacy Endpoint

AZ-104 was numerically superior to placebo in pain-relief at 2-hours post-dose, but these differences were not statistically significant. Pain relief was observed in 56% of patients receiving the 2.5 mg dose (p=0.11) and 54% of patients receiving the 1.25 mg dose (p=0.12), as compared to 45% of patients receiving placebo.

Another commonly used measure of efficacy in migraine studies is the percentage of patients who are pain-free at 2 hours post-dose. Again, AZ-104 was numerically superior to placebo in this measure, but the differences were not statistically significant. Pain-free responders were 31% of the patients receiving the 2.5 mg dose and 27% of the patients receiving the 1.25 mg dose, as compared to 23% of the patients receiving placebo.