British Journal of Psychiatry Publishes Results from Phase 3 Study of Alexza's AZ-004 for the Treatment of Agitation in Patients with Schizophrenia

AZ-004 demonstrated statistically significant reductions in agitation compared with placebo as assessed by primary and key secondary endpoints

AZ-004 was safe and well tolerated in this study

MOUNTAIN VIEW, Calif., Jan. 24, 2011 /PRNewswire/ -- Alexza Pharmaceuticals, Inc. (Nasdaq: ALXA) announced today that the British Journal of Psychiatry, a publication of the Royal College of Psychiatrists, has published the results of the pivotal Phase 3 study evaluating AZ-004 (inhaled or Staccato® loxapine) for the rapid treatment of agitation in patients with schizophrenia, in its January 2011 edition (198:51-58).

The Phase 3, randomized, double-blind, placebo-controlled, parallel-group study (ClinicalTrials.gov), conducted in 24 U.S. clinical centers, enrolled 344 patients with schizophrenia experiencing agitation.  Patients received one, two or three doses of AZ-004 (5 or 10 mg) or a placebo.  Alexza previously announced preliminary results from its two Phase 3 studies in late 2008.

"Individuals with schizophrenia are highly vulnerable to episodes of agitation.  Current treatment options are not optimal for managing these episodes," commented Dr. Michael D. Lesem, the publication's lead author, a principal investigator for the Phase 3 trial and Medical Director at Claghorn-Lesem Research Clinic, Houston, Texas.  "There is a clear need for novel anti-agitation treatments that are quick to act, safe and well tolerated, easy to administer and accepted by patients and staff.  In this study, inhaled loxapine provided a rapidly calming effect in agitated patients with schizophrenia."

The primary efficacy end-point of this study was change from baseline in PANSS (Positive and Negative Syndrome Scale) Excited Component score (also known as PEC score), measured at two hours after the first dose of study medication.  The PEC score is a summation of individual scores (from 1-7) across five items:  hostility, uncooperativeness, impulse control, tension, and excitement.  The range of possible PEC scores is 5 through 35.

PEC Scores (Mean Values)

 

Study Arm

Baseline

2-Hour Post-Dose

p-Value for change

from Baseline

vs. Placebo

 

10 mg AZ-004 (n=112)

17.6

9.0

<0.0001

 

5 mg AZ-004 (n=116)

17.8

9.8

0.0004

 

Placebo (n=115)

17.4

11.8

-

 
       


 

The key secondary end-point in the study was the Clinical Global Impression–Improvement scale (CGI–I) score, measured at two hours after the first dose of study medication.  The four-point scale measures improvement by the physician's assessment, where 1 is very much improved and 4 is no change.  A score of 2 is much improved.

CGI-I Scores (Mean Values)

 

 

 

 
 

Study Arm

2-Hour Post-Dose

p-Value

 

10 mg AZ-004 (n=112)

2.1

<0.0001

 

5 mg AZ-004 (n=115)

2.3

0.0015

 

Placebo (n=115)

2.8

-

 
     


 

Results of the study demonstrated that AZ-004 (both 5 and 10 mg) provided a statistically significant reduction in agitation compared to placebo, as assessed by the primary and key secondary end-points.  A statistically significant reduction in the PEC score was evident 10 minutes after dose one with both 5 and 10 mg doses, which was the first time point assessed in the study.  AZ-004 was well tolerated, and the most common adverse events were known effects of loxapine or minor oral effects common with inhaled medications.

"We are pleased to have this Phase 3 clinical trial published in a peer-reviewed journal of the caliber of the British Journal of Psychiatry," said Dr. James V. Cassella, Alexza Senior Vice President, Research and Development.  "Based on the results of the robust clinical development program for AZ-004 to date, we are looking forward to our planned resubmission of the AZ-004 NDA in the U.S. in July of this year and the submission of the MAA in Europe in the third quarter."

The open access article is available on the British Journal of Psychiatry's website at: http://bjp.rcpsych.org/cgi/content/full/198/1/51.

About Alexza Pharmaceuticals, Inc.

Alexza 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. (Click here to see an animation of how the Staccato system works.)

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 the AZ-004 NDA in December 2009.  In October 2010, the Company received a CRL from the FDA, regarding its NDA for AZ-004.  A CRL is issued by FDA's Center for Drug Evaluation and Research indicating that the NDA review cycle is complete and the application is not ready for approval in its present form.  The Company completed an end-of-review meeting with the FDA in late December 2010.  

The Company believes it has a clear understanding of the issues outlined in the CRL, is developing and executing a plan to address these issues and currently projects a resubmission of the AZ-004 NDA in July 2011.  

For more information about Alexza, the Staccato technology or the Company's development programs, please visit www.alexza.com.

Safe Harbor Statement

This press release includes forward-looking statements regarding the development and safety of the Company's product candidates and technologies.  Any statement describing the Company's 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.  The Company'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 forward-looking statements are based upon Alexza's current expectations.  Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of developing and commercializing drugs, including the potential of the Company's planned NDA resubmission to adequately address the issues in the CRL, the eventual prospects that AZ-004 will be approved for marketing and the timing of the Company's resubmission of the AZ-004 NDA to the FDA.  Alexza's actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks related to the uncertainty of the FDA approval process and other regulatory requirements, and the timing of completion of the steps necessary for resubmission of the NDA for AZ-004.  Alexza may be unsuccessful in resolving the issues in the CRL and it may never receive marketing approval for AZ-004 or any of its product candidates .  These and other risks concerning Alexza's business are described in additional detail in the Company's Annual Report on Form 10-K for the year ended December 31, 2009, and the Company's other Periodic and Current Reports filed with the Securities and Exchange Commission including the risks under the headings: "Regulatory authorities may not approve our product candidates even if they meet safety and efficacy endpoints in clinical trials.", "We have a history of net losses. We expect to continue to incur substantial and increasing net losses for the foreseeable future, and we may never achieve or maintain profitability.", and "We will need substantial additional capital in the future. If additional capital is not available, we will have to delay, reduce or cease operations.".  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: Derek K. Cole, Head, Investor Relations and Corporate Communications, Alexza Pharmaceuticals, Inc., +1-650-944-7373, dcole@alexza.com
 

Web Site: http://www.alexza.com
 

Posted: January 2011

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