Valeant announces Alexza's receipt of FDA CRL for AZ-004 NDA

Valeant Pharmaceuticals International, Inc. (NYSE: VRX) (TSX: VRX) announced today that Alexza Pharmaceuticals, Inc. (Nasdaq: ALXA) has received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) regarding Alexza's New Drug Application (NDA) for AZ-004 (Staccato® loxapine) submitted as Adusuve™ Staccato® (loxapine) inhalation aerosol, 5 mg and 10 mg.  Valeant's subsidiary, Biovail Laboratories International SRL (BLS), entered into a collaboration and license agreement with Alexza Pharmaceuticals, Inc. in February 2010 for the U.S. and Canadian rights to commercialize AZ-004.  AZ-004 is being developed for the rapid treatment of agitation in patients with schizophrenia or bipolar disorder.  

A CRL is issued by the FDA's Center of Drug Evaluation and Research indicating that the NDA review cycle is complete and that the application is not ready for approval.  In the CRL received by Alexza, the FDA stated that their primary clinical safety concern was related to data from three Phase I pulmonary safety studies with AZ-004.  This concern was based on observed, dose-related post-dose decreases in forced expiratory volume in one second, or FEV1, a standard measure of lung function, in healthy subjects, and in subjects with chronic obstructive pulmonary disease (COPD) and asthma.  Alexza intends to meet with the FDA in the near future to discuss steps necessary to address this FDA concern.  Alexza has previously reported that there were no serious or severe respiratory adverse events in these trials or reported in the two Phase III clinical trials of AZ-004.  All respiratory symptoms that developed after treatment in Phase I subjects with COPD and asthma were either self-limiting or readily managed with an inhaled bronchodilator.

The CRL also raised issues relating to the suitability of the stability studies undertaken by Alexza and certain other items relating to the FDA's recently completed pre-approval manufacturing inspection.  Because AZ-004 incorporates a novel delivery system, the CRL also included input from FDA's Center for Devices and Radiological Health (CDRH).  CDRH requested a human factors study and related analysis to validate that the product can be used effectively in the proposed clinical setting.  CDRH also requested further bench testing of the product under an additional "worst-case" manufacturing scenario.