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Inhaled, fast-acting loxapine to treat schizophrenia agitation to be reviewed by US FDA: Alexza

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Tuesday, December 15, 2009, 11:13 This news item was posted in health category and has 0 Comments so far.

Agitation episodes are currently treated with oral antipsychotics and  intra-muscular injections

An inhaled schizophrenia drug Staccato loxapine to control violent agitation in patients by Alexza Pharmaceuticals, Inc, may well be around the corner.

Alexza Pharmaceuticals has submitted its New Drug Application (NDA) for investigational Staccato loxapine titled AZ-004 to the US Food and Drug Administration, the company announced.

Staccato loxapine, a drug belonging to the class of compounds known generally as antipsychotics, is an inhalation product candidate being developed for the rapid treatment of agitation in patients with schizophrenia or bipolar disorder.

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.

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, according to Alexa.

Schizophrenia and bipolar 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.

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.

The Investigational New Drug (IND) for Staccato loxapine was filed with the FDA in August 2005.

Alexza’s proprietary Staccato system with loxapine. 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.

Staccato loxapine has established consistent safety and efficacy profile in treating patients with agitation, revealed 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,” he stated in a company release.

Staccato loxapine could be cleared for sale in US markets by 2010, hoped Alexza.

Staccato loxapine has been studied for efficacy and safety data in more than 1600 patients and subjects in thirteen different clinical trials.

Alexza started two pivotal Phase 3 clinical trials for Staccato loxapine in 2008. In these studies, both doses of Staccato loxapine (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 Staccato loxapine 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 Staccato loxapine was generally safe and well tolerated.

In 2009, Alexza initiated and completed five non-pivotal safety and NDA-supporting studies for AZ-004.

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.

AZ-004 (Staccato loxapine) is Alexza’s lead program. 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.

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