Alexza Pharmaceuticals, Inc., a wholly-owned subsidiary of Ferrer Therapeutics, Inc., has announced that its supplemental New Drug Application (sNDA) seeking certain changes in the product label and modifications to the Risk Evaluation Mitigation Strategy (REMS) Program for ADASUVE®(loxapine) inhalation powder (10mg) has been approved by the U.S. Food and Drug Administration (FDA). ADASUVE is the first and only orally inhaled medicine for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults.
ADASUVE is administered through Alexza's innovative proprietary Staccato® single-use, hand held drug delivery technology system. The Staccato system allow for rapid systemic delivery by inhalation of a thermally-generated aerosol of loxapine, a first generation antipsychotic, to the lung. Administration of ADASUVE results in rapid absorption of loxapine, with a maximum plasma concentration achieved in approximately 2 minutes.
The original FDA approval of ADASUVE was based on the clinical efficacy of inhaled loxapine, demonstrated in two pivotal clinical trials of treating acute agitation: one in patients with schizophrenia and one in patients with bipolar I disorder. Patients receiving ADASUVE experienced a statistically significant reduction in agitation at two hours, the primary endpoint of the studies. These studies demonstrated a 49% reduction in agitation symptoms from baseline in schizophrenia patients, as compared to 33% in patients receiving placebo; and a 53% reduction from baseline in bipolar I patients, as compared to 27% in patients receiving placebo. In these two studies, reduction of agitation was rapidly achieved at 10 minutes post-dose, the first time point studied in the trials, with a 19% reduction in agitation from baseline in schizophrenia patients and a 23% reduction in bipolar I patients, both as compared to 10% in patients receiving placebo.
The approved sNDA includes changes to the prescribing information and modifications to the ADASUVE REMS. The approved product label changes and corresponding REMS modifications include removal of the requirement for immediate access on-site to equipment and personnel trained to manage acute bronchospasm, including advanced airway management (intubation and mechanical ventilation). As modified by the sNDA, the updated ADASUVE label and REMS require that certified Health Care Settings must have immediate access on-site to supplies and personnel trained to manage acute bronchospasm and ready access to emergency response services. Facilities must have a short-acting bronchodilator, including a nebulizer and inhalation solution, for immediate treatment of bronchospasm.
The labeling changes consist of revisions to the Boxed Warning and Warning and Precautions sections of the Prescribing Information.