Adasuve

Treatment for Agitation, Schizophrenia, Bipolar Disorder

Update: Adasuve (loxapine) Now FDA Approved - December 21, 2012

NDA Submitted for AZ-004 (Staccato Loxapine)

Alexza Announces Submission of AZ-004 (Staccato Loxapine) NDA

MOUNTAIN VIEW, Calif., Dec. 14 /PRNewswire-FirstCall/ -- Alexza Pharmaceuticals, Inc. 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.

About AZ-004 (Staccato loxapine)

AZ-004 is an anti-agitation therapeutic that combines Alexza's proprietary Staccato system with loxapine, a drug belonging to the class of compounds known generally as antipsychotics. Loxapine is currently available in an oral formulation in the United States for the management of the manifestations of schizophrenia. The Staccato system is a hand-held, chemically-heated, single-dose inhaler that delivers a pure drug aerosol to the highly vascularized tissues of the deep lung.

As an easy-to-use, patient-controlled, and highly reliable therapeutic that provides rapid reduction in agitation, the Company believes that AZ-004 meets the three key attributes for the treatment of acute agitation as specified in the American Association of Emergency Psychiatrists' Expert Consensus Guidelines for the Treatment of Behavioral Emergencies: speed of onset, reliability of medication delivery and patient preference.

About Alexza Pharmaceuticals, Inc.

Alexza Pharmaceuticals is a pharmaceutical company focused on the research, development and commercialization of novel, proprietary products for the acute treatment of central nervous system conditions. Alexza's technology, the Staccato system, vaporizes unformulated drug to form a condensation aerosol that, when inhaled, allows for rapid systemic drug delivery through deep lung inhalation. The drug is quickly absorbed through the lungs into the bloodstream, providing speed of therapeutic onset that is comparable to intravenous administration, but with greater ease, patient comfort and convenience.

AZ-004 (Staccato loxapine) is Alexza's lead program, which is being developed for the rapid treatment of agitation in schizophrenic or bipolar disorder patients. Alexza has completed and announced positive results from both of its AZ-004 Phase 3 clinical trials, and submitted a New Drug Application submission in December 2009.

Alexza has completed an end-of-Phase 2 meeting with the FDA for AZ-001 (Staccato prochlorperazine) and has completed two Phase 2 studies with AZ-104 (Staccato loxapine, low-dose). Both product candidates are being developed for the acute treatment of migraine headache.

AZ-002 (Staccato alprazolam) has completed Phase 1 testing and one Phase 2a proof-of-concept clinical trial. Product candidates that have completed Phase 1 testing are AZ-003 (Staccato fentanyl) for the treatment of breakthrough pain, and AZ-007 (Staccato zaleplon) for the treatment of insomnia. More information, including this and past press releases from Alexza, is available online at www.alexza.com.

Safe Harbor Statement

This press release includes forward-looking statements regarding the development, therapeutic potential and safety of AZ-004. Any statement describing a product candidate or Alexza's goals, expectations or beliefs is a forward-looking statement, as defined in the Private Securities Litigation Reform Act of 1995, and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of developing and commercializing drugs. Alexza's forward-looking statements also involve assumptions that, if they prove incorrect, would cause its results to differ materially from those expressed or implied by such forward-looking statements. These and other risks concerning Alexza's business are described in additional detail in Alexza's Annual Report on Form 10-K for the year ended December 31, 2008, and Alexza's other Periodic and Current Reports filed with the Securities and Exchange Commission, including the risks under the headings: "We will need substantial additional capital in the future. If additional capital is not available, we will have to delay, reduce or cease operations.", "Regulatory authorities may not approve our product candidates even if they meet safety and efficacy endpoints in clinical trials." and "If we do not establish strategic partnerships, we will have to undertake development and commercialization efforts on our own, which would be costly and delay our ability to commercialize any future products". Forward-looking statements contained in this announcement are made as of this date, and we undertake no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

Source: Alexza Pharmaceuticals, Inc.

CONTACT: Thomas B. King, President & CEO, +1-650-944-7634, tking@alexza.com, or August J. Moretti, Senior Vice President and CFO, +1-650-944-7788, amoretti@alexza.com, both of Alexza Pharmaceuticals, Inc.

Web Site: http://www.alexza.com/

Posted: December 2009

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