FDA delays Alexza’s inhaled antipsychotic on 'major’ NDA amendment
This article was originally published in Scrip
The US FDA declared Alexza Pharmaceuticals' update to its proposed risk evaluation and mitigation strategy (REMS) plan a major amendment to the firm's new drug application (NDA) for Adasuve (loxapine), an inhaled antipsychotic under investigation to treat agitation associated with schizophrenia or bipolar disorder in adults – resulting in the agency’s decision on the NDA being delayed by three months.
Regulators have moved the Prescription Drug User Fee Act for the NDA from 4 February to 4 May, the Mountain View, California firm said.
Investors reacted by pushing shares of Alexza down as low as 18.8% on 23 January, before the stock closed at 77 cents, a loss of 3 cents, or 3.8%.
Alexza said it submitted the amendment to the REMS to address issues raised during the 12 December 2011 meeting of the FDA's Psychopharmacologic Drugs Advisory Committee (PDAC), which split 9-8, with one abstention, on backing approval of the drug.
While the PDAC found no problem with Adasuve's efficacy – voting 17-1 that the drug had been shown to be effective for the proposed indication – the panel of psychiatrists, pulmonologists, pharmacists, a psychopharmacologist, a statistician, a drug safety expert and consumer and patient representatives was concerned about the potential for pulmonary toxicity with the experimental inhaled medicine, particularly in patients with pre-existing airway disease, such as asthma or chronic obstructive pulmonary disease (COPD) (scripintelligence, 13 December 2011, 9 December 2011).
Indeed, in Alexza's pulmonary safety studies, 58% of COPD and 69% of those with asthma experienced significant respiratory signs or symptoms, versus 22% and 12% for the placebo groups, respectively.
Although the company had proposed its own REMS, the FDA came up with an alternative plan.
The PDAC, which found the option of a fast-acting inhaled medication much more appealing than having a patient in an agitated state deal with the pain and discomfort of getting stuck with a needle to administer intramuscular shots of antipsychotics, voted 11-5, with two abstentions, in December that if Adasuve was limited to a single dose in 24 hours, the drug was acceptably safe to treat agitation in patients with schizophrenia or bipolar mania when used in conjunction with the REMS proposed by the FDA.
Alexza's drug is delivered with the firm's Staccato single-use, hand-held device. When a patient inhales on the device, it triggers the controlled rapid heating of a thin film of loxapine to form a drug vapor, which condenses to aerosol sized particles for delivery to the deep lung, with expectation of rapid systemic delivery. The drug has been shown to work within 10 minutes.
"We continue to believe that we are on a pathway to gain approval of Adasuve in the United States," Alexza CEO Thomas B King said.