A Food and Drug Administration advisory committee review of Alexza Pharmaceuticals’ inhalable schizophrenia treatment Adasuve (loxapine) will focus on the drug’s pulmonary safety and the adequacy of a proposed Risk Evaluation and Mitigation Strategy to address this concern.
The Psychopharmacologic Drugs Advisory Committee will meet on Dec. 12 to discuss safety and efficacy issues for Adasuve, which is being proposed for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults. The FDA’s meeting notice, published in the Federal Register on Oct. 24, cites pulmonary safety concerns as a particular issue for discussion.
Loxapine is an antipsychotic approved in oral and injectable forms. Adasuve uses Alexza’s Staccato system to vaporize the drug for deep lung inhalation and rapid treatment of agitation in schizophrenic and bipolar patients. Alexza is proposing the drug be used only in medically supervised settings, such as hospitals or psychiatric facilities.
Adasuve’s novel delivery form for an antipsychotic has posed some regulatory problems.
The new drug application was the subject of an October 2010 "complete response" letter that raised pulmonary safety concerns due to data from three phase I pulmonary safety studies. In those studies, healthy subjects and subjects with asthma or chronic obstructive pulmonary disease experienced dose-related, post-dose decreases in lung function, as measured by forced expiratory volume in 1 second. Lung function decreases also were recorded in subjects given the device-only placebo control.
The letter also cited issues with stability data. The Center for Devices and Radiological Health, which is providing input on the NDA review because of the inhalation device, requested a human factors study be conducted to provide assurance that the drug can be used effectively in the proposed clinical setting.
Following a December 2010 end-of-review meeting with the agency, Alexza said it would submit a proposed Risk Evaluation and Mitigation Strategy (REMS) aimed at ensuring that the drug is not prescribed to schizophrenics who may be susceptible to pulmonary adverse events.
The NDA was resubmitted in August with a REMS that includes a communication plan and various voluntary measures, such as an information checklist for screening patients with active airway disease who are at increased risk for bronchospasm. However, the REMS lacks elements to assure safe use.
Alexza CEO and President Tom King told "The Pink Sheet" that the REMS is aimed at screening patients to ensure those with active airway disease are not prescribed the drug. However, it also contains two "safety nets" in the event that patients with preexisting pulmonary problems are inappropriately given inhalable loxapine.
The REMS calls for patients to be observed for occurrence of respiratory adverse events for 1 hour after dosing and for inhaled albuterol to be readily accessible as a rescue medication to treat adverse reactions.
This coverage is provided courtesy of "The Pink Sheet." This news organization and "The Pink Sheet" are owned by Elsevier.