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FDA rejects Alexza's NDA for inhaled antipsychotic

Friday, May 04 2012 | Comments
Evidence Grade 0 What's This?
The Food and Drug Administration sent Alexza Pharmaceuticals Inc. another complete response letter denying the company's request for approval of Adasuve (loxapine) inhalation powder for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults.

Adasuve is a novel formulation of loxapine administered via deep lung inhalation using Alexza's proprietary Staccato device. Had it been approved, Adasuve would have been the first drug based on the Staccato technology platform to make it to the market.

Alexza originally submitted the New Drug Application (NDA) for 5 mg and 10 mg doses of Adasuve in December 2009. The FDA sent a complete response letter to Alexza in October 2010 voicing concerns about pulmonary safety data from three Phase I trials that included healthy participants and patients with chronic obstructive pulmonary disease (COPD) and asthma. The company resubmitted the NDA last August with new data to address the agency's concerns, updated draft labeling and a risk evaluation and mitigation strategy (REMS).

The FDA, however, said the resubmitted application is not ready for approval in its present form, according to Alexza. The latest complete response letter states that during a recent inspection of Alexza's Mountain View, Calif., manufacturing facility, a field investigator observed deficiencies at the facility.

"Satisfactory resolution of these deficiencies is required before this application may be approved," the FDA wrote in the letter.

Alexza believes the deficiencies are "medical device specific" and can be readily addressed. The company intends to meet with the FDA to further discuss the specific deficiencies, noting that such a meeting would be scheduled "as soon as practical." 

The FDA did not identify any new clinical or safety issues and no other deficiencies were mentioned in the letter, Alexza said. The agency stated in the letter that discussions could continue on the proposed REMS after the company has submitted its response to the agency's complete response letter, and the FDA also commented on Alexza's proposed product labeling. Alexza said it believes there is substantial agreement between the company and the FDA on the REMS and product labeling.

Last December, the FDA's Psychopharmacologic Drugs Advisory Committee recommended approval of the drug as a treatment for agitation in patients with schizophrenia or bipolar disorder. The panel of experts voted 9-8, with one abstention, that Adasuve be approved for use as a single dose in 24 hours and that it be used in accordance with a REMS.

Prior to that meeting, FDA staff reviewers had warned that Adasuve might cause respiratory failure. The reviewers said the drug posed "a significant risk of bronchospasm, particularly in patients with pre-existing airway disease, such as asthma and COPD."

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