Alexza Pharmaceuticals Inc. (ALXA)’s inhaled antipsychotic drug may put some patients at risk for respiratory failure, according to U.S. regulators considering whether to approve the treatment for sale.
While Adasuve is effective as a fast-acting treatment for agitation among patients with schizophrenia and bipolar disorder, it can cause bronchial spasms that may be fatal in people with conditions such as asthma, Food and Drug Administration staff said today in a report. Outside advisers to the agency plan to meet Dec. 12 to evaluate the findings.
Adasuve would be the first product for Mountain View, California-based Alexza. The therapy uses an inhalation device developed by the company to deliver a vaporized form of the antipsychotic medication loxapine to the lungs for rapid absorption into the bloodstream. The FDA aims to decide on the product by Feb. 4.
“It is likely that, even with adequate screening for pulmonary risk factors, some patients will require respiratory support post-dose, and some patients will be at risk for respiratory failure and death,” FDA staff said.
The drug, if approved, should only be administered by professionals who have intubation tubes and ventilators “readily available,” according to the report.
Adasuve failed to win FDA approval in October 2010, because the agency was concerned about risks of pulmonary toxicity, particularly in patients with asthma or chronic obstructive pulmonary disorder.
Risk Mitigation Plan
Alexza resubmitted its application in August with a proposed risk-mitigation strategy that includes screening patients to identify those at risk for lung problems and monitoring people who take Adasuve for an hour after treatment.
Those proposals didn’t resolve FDA reviewers’ concerns because it may be difficult for health-care providers to monitor psychiatric patients for early signs of bronchial spasms, the report said.
“Psychotic and agitated patients who develop respiratory symptoms may not be able to notify health-care personnel in a timely manner, and respiratory distress may be confused with acute agitation to the casual observer,” agency staff said. The drug’s sedating effect “may also mask respiratory signs and symptoms while causing further respiratory suppression.”
The FDA asked its Psychopharmacologic Drugs Advisory Committee to weigh in on Adasuve’s effectiveness and safety, and on whether Alexza’s risk-mitigation proposal is sufficient to ensure the benefits of the drug justify its risks.
A company-funded study published in January in the British Journal of Psychiatry found that Adasuve started to work within 10 minutes of inhalation and was more effective than a placebo in cutting agitation levels within two hours.
There haven’t been any studies directly comparing Adasuve with other drugs approved to treat agitation in patients with schizophrenia and bipolar disorder, the FDA reviewers said.
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