The FDA’s Psychopharmacologic Drugs Advisory Committee voted 12 to 2 that the benefits of Acadia Pharmaceuticals’ pimavanserin (Nuplazid) outweigh the risks in treatment of Parkinson’s disease psychosis.
The drug was previously granted priority review and breakthrough therapy status, with an action date of May 1, 2016.
While the vote does not directly recommend approval, it does suggest that the committee felt the drug was efficacious and the safety profile was well-characterized.
Members of the committee expressed reservations about efficacy and safety of the drug, especially regarding off-label use, but the need for an effective treatment appeared to outweigh concerns. “… given the lack of alternatives and the poor quality of life in this condition, I think that explained the majority of endorsements for the favorable risk-benefit ratio,” said chairperson David Brent, MD, of the University of Pittsburgh.
There are currently no other approved treatments for psychosis associated with Parkinson’s disease. Typical antipsychotics including olanzapine, quetiapine, and risperidone are currently used off-label to treat symptoms, however these drugs adversely interact with dopamine, which is most commonly used to treat the motor symptoms of Parkinson’s. Alternately, Nuplazid is a once-daily selective serotonin inverse agonist that targets 5-HT2A receptors with no known adverse impacts on motor symptoms.
Committee members also expressed concerns based on the available trial data: a single, positive phase 3 pivotal trial that evaluated efficacy, tolerability, and safety, and 3 randomized controlled trials that did not reach significance for the primary endpoint. The positive trial employed the Schedule for the Assessment of Positive Symptoms- Parkinson’s Disease (SAPS-PD) to measure improvement, though the scale had not previously been deployed. Overall, there was an approximate 23% improvement in psychotic symptoms with Nuplazid compared with placebo – results that were deemed “minimal improvements” when assessed on the Clinical Global Impressions scale. Members also expressed concern for the 2-fold increase in risk of serious adverse events, including death, when taking Nuplazid compared with placebo.
“Patients need to make an informed decision, but with the data we have today they cannot,” said Almut Winterstein, PhD, RPh, of the University of Florida, who voted “yes.” “I recommend that the FDA does a phase IV study to allow patients to make that decision.”
Still, most members appeared to be swayed by the growing need for treatment for this particularly detrimental symptom, which occurs in as many as 40% of Parkinson’s patients and is associated with nursing home placement and increased morbidity and mortality risk.
“I’m persuaded that there really is nothing else,” Dr Brent said. “Although the effects are modest, we have to compare that with what’s available right now, and that’s nothing.”