Alexza Pharmaceuticals, Inc announced it has completed enrolment of its second phase-3 clinical trial of AZ-004 (Staccato loxapine), treating acute agitation in patients with bipolar disorder. AZ-004 is an inhalation product candidate being developed for the treatment of acute agitation in patients with schizophrenia or bipolar disorder.

In September, Alexza announced positive results from the first of two planned AZ-004 phase-3 studies -- treating patients with schizophrenia -- showing that both the 5 mg and 10 mg doses of AZ-004 met the primary endpoint of the trial, which was a statistically significant reduction in agitation from baseline to the two-hour post-dose time point, compared with placebo. The second AZ-004 phase-3 clinical trial is similar in design and scope. Initiated in July 2008 with a target enrolment of 300 patients, 314 patients were enrolled and Alexza expects to announce top line results by the end of this year. AZ-004 is being developed through Symphony Allegro, a product development partnership formed between Alexza and Symphony Capital LLC in 2006.

"The AZ-004 programme continues to progress rapidly, efficiently and productively," said Thomas B King, Alexza president and CEO. "With our second AZ-004 phase-3 trial now enrolled, we are two years ahead of our original schedule. If data from this second phase-3 trial are also positive, we expect to submit Alexza's first NDA early in 2010."

King noted that at the time of establishing Symphony Allegro in December 2006, the AZ-004 development timeline projected an end-of-phase-2 meeting with the FDA by the end of 2009.

"AZ-004 has made remarkable progress in the clinic," King said. "Patients, physicians and nurses have embraced it, speeding our enrolment and execution of the trial protocols. Moreover, the clinical results thus far indicate that AZ-004 may have the potential to establish a new treatment paradigm for treating patients with acute agitation."

"No approved product has the three attributes the experts say are necessary to optimally treat acute agitation; onset of effect, reliability of medication delivery and patient preference (in this case, the avoidance of an injection and easy self-administration)," King continued. "AZ-004 appears to have demonstrated these key attributes in the clinic, and if it is approved, we believe it could provide a very valuable new tool for clinicians to treat acute agitation in these patient populations."

King also explained that the rapid clinical progress of AZ-004 has spurred the company to accelerate its commercial development and planning.

"With two pivotal AZ-004 Phase 3 studies initiated and completed during 2008, Alexza will sharpen its focus on AZ-004, and step up activities for commercial manufacturing, quality systems, regulatory submissions, and potential sales and marketing," he said. "Driving this product through NDA submission and, if approved, a successful product launch is our top priority."

"We believe a primary focus on AZ-004 development makes sense for the company and its stockholders," King said. "Our lead product candidate has demonstrated that Alexza's Staccato technology has clinical viability, possibly significant commercial value, and is close to the NDA goal line. We believe our technology and the product candidates we have under development can fundamentally improve, and in some cases change, the way many acute and intermittent conditions are treated. We are committed to building a broad portfolio of Staccato-based products that will capitalize on this potential. At the same time, we are critically aware of the very difficult capital markets, and the need to prioritize and focus on what we believe are key near-term value-drivers."

"In practice," King explained, "This means that over the next 12 months, in addition to our AZ-004 activities, we will continue to push forward our partnered and funded programs, with Endo Pharmaceuticals for AZ-003 (Staccato fentanyl) for breakthrough pain and with Symphony Allegro for AZ-104 (Staccato loxapine, in a low-dose form) for migraine."

Alexza recently completed an end-of-phase-2 meeting with the FDA for AZ-001 (Staccato prochlorperazine) and the company believes it has a clear understanding of the NDA requirements for this product candidate. Consistent with previous guidance, Alexza is not planning on conducting any phase-3 studies on AZ-001 without a partner, and Alexza is continuing to seek partners for our Staccato migraine product candidates, AZ-001 and AZ-104.

AZ-004 is the combination of Alexza's proprietary Staccato system with loxapine, a drug belonging to the class of compounds known generally as antipsychotics.

In December 2006, Alexza entered into a collaboration with Symphony Capital LLC, a biotech-focused private equity firm. Alexza Pharmaceuticals is an emerging specialty pharmaceutical company focused on the development and commercialization of novel, proprietary products for the treatment of acute and intermittent conditions.