Alexza Pharmaceuticals submits its NDA for Staccato loxapine to FDA

Alexza Pharmaceuticals, Inc. (Nasdaq: ALXA) today announced that it has submitted its New Drug Application (NDA) for Staccato® loxapine (AZ-004) to the US Food and Drug Administration (FDA). AZ-004 is an inhalation product candidate being developed for the rapid treatment of agitation in patients with schizophrenia or bipolar disorder. The IND for Staccato loxapine was filed with the FDA in August 2005.

"AZ-004 has delivered a predictable and consistent safety and efficacy profile in treating patients with agitation," said James V. Cassella, PhD, Senior Vice President, Research and Development at Alexza. "We believe that AZ-004, if approved, has the potential to change the treatment practices for acute agitation, as the only product able to meet both the patients' desire for quickly and comfortably gaining control, and the clinicians' goal of rapidly and reliably calming an agitated patient."

"The data we have seen from the Staccato loxapine trials are compelling," said Michael Lesem, MD, Executive Medical Director, Claghorn-Lesem Research Clinic, Houston, TX. "The product exhibits a rapid and predictable reduction in agitation, and appears to have a favorable safety profile in these patient populations."

"We once again exceeded our corporate goal timeline with the AZ-004 NDA submission," said Thomas B. King, President and CEO of Alexza. "The continued concentrated effort of the entire Alexza team throughout 2009 has been nothing short of remarkable and allowed us to complete this landmark milestone for the company. We eagerly look forward to 2010, as we work toward the approval of this product candidate."

"When Alexza was founded, I had the vision that its proprietary technology had the potential to improve the therapeutic value of drugs," said Alejandro C. Zaffaroni, PhD, Chairman Emeritus and Co-Founder of Alexza. "It is splendid that Alexza has reached its first NDA so quickly and is on the doorstep of its first Staccato-based product, Staccato loxapine."

AZ-004 Clinical Results Summary

The AZ-004 NDA contains efficacy and safety data from more than 1600 patients and subjects who have been studied in thirteen different clinical trials. In 2008, the Company successfully initiated and completed two pivotal Phase 3 clinical trials. In these studies, both doses of AZ-004 (5 and 10 mg) met the primary and key secondary endpoints of the studies, with highly statistically significant reductions in agitation, as compared to placebo. Additionally, the 10 mg dose of AZ-004 exhibited a rapid onset of effect, with statistically significant reductions in agitation at 10 minutes post-dose, the first time point measured. The reduction of agitation was sustained through the 24-hour study period. In both studies, the administration of AZ-004 was generally safe and well tolerated.

In 2009, Alexza initiated and completed five non-pivotal safety and NDA-supporting studies for AZ-004. Alexza believes these data, along with data from the other efficacy and safety trials conducted with AZ-004, adequately demonstrate the efficacy and safety of AZ-004 for the proposed indication.

Agitation Market Opportunity

Episodes of agitation afflict many people suffering from major psychiatric disorders, including schizophrenia, which affects approximately 2.4 million adults in the United States, and bipolar disorder, which affects approximately 5.7 million adults in the United States. More than 90% of these patients will experience agitation in their lifetime.

Agitation generally escalates over time with patients initially feeling uncomfortable, tense and restless. As the agitation intensifies, their behavior appears more noticeable to others as they become threatening and potentially violent, especially if the agitation is not treated. While patients seek treatment at different points along this agitation continuum, those with the most severe symptoms generally require treatment with injectable drugs in emergency medical settings, and currently are thought of to represent the agitation market. Alexza, however, believes the therapeutic market for agitation is broader than only this limited perspective of patients in severe crisis -- many more are in need of treatment for an agitation episode.

Alexza's primary market research indicates that approximately 50% of treated acute agitation episodes are treated in emergency settings. Another approximately 35% of the treated agitation episodes suffered by schizophrenic and bipolar patients are treated in an inpatient setting (hospital and long-term residential settings), and approximately 15% are treated in a physician's office.

Alexza's market research studies with schizophrenia patient caregivers and bipolar patients indicate these patients currently experience an average of 11 to 12 episodes of acute agitation each year.

Agitation episodes are currently treated about 55% of the time with oral antipsychotics and about 45% of the time with intra-muscular, or IM, injections. Oral medications work relatively slowly, but are easy to administer, painless and are less threatening to patients. IM injections have a faster onset of action and a higher predictability of drug effect, but because they are invasive and can be frightening to patients, IM injections are usually the treatment option of last-resort. Currently, no non-invasive therapies are available that work faster than 30 minutes to help agitated patients in need of treatment.