Ten months after a surprising FDA rejection and after at least three subsequent meetings, Acadia Pharmaceuticals is back with a refiling of antipsychotic drug Nuplazid. This time, it’s seeking approval for a smaller patient population—but even that constraint is riddled with regulatory uncertainties.
Instead of a broad indication for dementia-related psychosis, Acadia is now seeking the FDA’s blessing for Nuplazid specifically for hallucinations and delusions associated with Alzheimer’s disease psychosis, the company said Wednesday.
The resubmission came after a complete response letter last April, prompting the company to lament a sudden about-face from the FDA. Despite a prior agreement centered on a clinical trial analysis for the overall psychosis population, the agency instead asked Acadia to prove Nuplazid’s effect in patient subgroups, the company said.
But instead of running any new clinical trials, Acadia is taking a second shot at the indication based on an analysis of existing data in a narrower label.
Still, the company’s new Alzheimer’s disease psychosis pursuit marks a “robust opportunity” as it's the largest subtype of dementia-related psychosis, with about 70% representation, RBC Capital Markets analyst Gregory Renza, M.D., said in a December note. But that approach still leaves some questions behind.
Since the rejection, the FDA has advised Acadia that the best path forward is to conduct an additional clinical trial in each of the patient subgroups. That’s because the phase 3 trial Acadia used, dubbed Harmony, wasn’t statistically powered to run formal subgroup calculations.
Nevertheless, according to Acadia, the agency did say it was open to reviewing a new application based on additional analyses of existing data from Harmony and a phase 2 trial specifically done in patients with Alzheimer’s disease psychosis (ADP). Those studies now form the basis of Acadia’s resubmission.
In an exploratory analysis of the ADP subgroup in the Harmony trial, Nuplazid takers were about 40% less likely to experience a relapse of psychotic symptoms compared with the placebo group. Again, the number doesn’t carry the rigor of statistical significance.
The FDA now has 30 days to decide whether to accept the new application package. Accepting an application for review isn’t a guarantee for approval.
“[W]e continue to sense that humble confidence from [Acadia] regarding the FDA interaction takeaways and the reviewability of the data package in ADP—a cautious optimism but deliberate approach on this refile,” Renza wrote in a Wednesday note.