ADELPHI, MD. – A Food and Drug Administration advisory panel on Dec. 12 narrowly recommended approval of an inhaled, rapidly acting formulation of the antipsychotic loxapine for the treatment for agitation in patients with schizophrenia or bipolar disorder.
The FDA’s Psychopharmacologic Drugs Advisory Committee voted 17-1 that the inhaled formulation of loxapine, an antipsychotic that was approved in 1975, had been shown to be effective for the proposed indication: the acute treatment of agitation associated with schizophrenia or bipolar disorder in adults.
But the panel voted 9-8 with 1 abstention, that inhaled loxapine should be approved for use as a single dose in 24 hours with an FDA-proposed risk management plan that addresses the increased risk of treatment-associated bronchospasm, particularly in patients with asthma. Those voting in favor of approval said they felt comfortable with the FDA’s proposed risk management plan and cited the need for such a treatment in patients with schizophrenia and bipolar disorder. Those voting against approval, however, expressed concern about safety – even when treatment was restricted to one dose over 24 hours and with the Risk Evaluation and Mitigation Strategy (REMS) proposed by the FDA – and said that more real-world safety data in emergency departments were needed before approval.
In two phase III studies of almost 800 acutely agitated patients with long-standing bipolar disorder or schizophrenia, treatment with loxapine had a significantly greater impact on reducing agitation within 2 hours than did placebo, with an effect that was first noticeable within 10 minutes of administration, according to the manufacturer, Alexza Pharmaceuticals. In the study, which did not include patients with pulmonary diseases, four patients in the treatment group had airway-related adverse reactions, compared with none in the placebo group
Pulmonary safety studies in patients with asthma and COPD showed that pulmonary function, as measured with spirometry, was reduced in loxapine-treated patients, compared with placebo-treated patients, particularly among those with asthma.
Concerns that bronchospasm in agitated patients could go unrecognized and could progress in patients who were successfully treated, prompted the FDA to propose a REMS that would limit the drug’s use to settings capable of providing advanced airway management, along with other requirements that were more stringent than the REMS plan proposed by Alexza.
If loxapine is approved, Alexza plans to market it as Adasuve inhalation powder. Several injectable formulations of antipsychotics are approved for agitation in these populations; Adasuve would be the first inhaled treatment for agitation in this population.
The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists were cleared of potential conflicts of interest related to the topic of the meeting.