Acadia Pharmaceuticals said Monday that it is ending a trial of Nuplazid in dementia-related psychosis early on the recommendation of the study’s data-monitoring committee, based on clear signs of effectiveness. The company said it will ask the Food and Drug Administration to add this indication to the product’s label in 2020.The product is approved as the only drug for Parkinson’s disease-related psychosis and, if approved in the new indication, it would be the only one for dementia patients. However, Nuplazid failed in a broad trial in schizophrenia in July.Shares in the San Diego, California-based biotech jumped 65% Monday, trading at $39.27 apiece. They peaked at $48.75 in July 2015.
While Alzheimer’s disease and other types of dementia remain stubbornly resistant to disease-modifying therapies, Acadia’s Nuplazid (pimavanserin) at least appears to have been able to treat one side effect of the neurodegenerative condition. Patients with dementia can experience hallucinations and delusions, estimated to occur in around 41% of Alzheimer’s patients, which can hasten admission to nursing homes.
With an approval already in the bag for the treatment of hallucinations and delusions from Parkinson’s disease psychosis, Acadia has been working to expand the number of indications on Nuplazid’s label. Treating schizophrenia in patients who don’t respond well to antipsychotic therapy was one target, though a Phase 3 study ultimately misfired.
However, treating hallucinations and delusions in Alzheimer’s patients turned out more successful, and that may not have been a surprise given the similarities to Parkinson’s disease psychosis.
The Phase 3 HARMONY trial first stabilized patients over 12 weeks by treating them with 34 mg of pimavanserin daily, the same as the Parkinson’s disease dose, and then randomizing responders to either continue on the drug or move to placebo. Patients were then followed for signs of relapse, defined as hospitalization, increase in symptoms, withdrawal from treatment or use of standard antipsychotic medication.
At an interim review, HARMONY’s data monitoring committee ruled that the trial met statistical criteria to stop early because of clear signs that pimavanserin delayed relapses.
Pimavanserin has gained breakthrough therapy designation with the FDA, a status that could speed its regulatory review. The early trial stop may add a persuasive case to agency reviewers, given the high statistical standard necessary for a data monitoring committee to make such a decision.
Still, Stifel analyst Paul Matteis cautioned that the FDA may want more data. “In other psychiatric indications we’ve been unable to find precedent where a single relapse-prevention [Phase 3] study is enough for a drug approval,” he wrote in a Sept. 9 note to clients.
Acadia has two other active programs for pimavanserin. A Phase 2 trial that completed enrollment in April is testing the drug as an adjunct treatment for the “negative symptoms” of schizophrenia. Another, Phase 3 study is looking at whether pimavanserin works as an adjunct treatment in major depressive disorder.
