Acadia unveils the positive PhIII it's taking to FDA for expanding Nuplazid's use in psychosis
Acadia Pharmaceuticals has broken out the numbers propping up Nuplazid’s surprise early win in a Phase III dementia study and, according to one analyst, it’s “as good as we could have hoped for.”
The biotech stunned investors three months ago when they announced they’re halting the HARMONY trial, having obtained enough positive data at an interim readout to make a pitch to the FDA. It came as a surprise and stirred up a rally around Acadia’s stock $ACAD, which has suffered from previous failed attempts at expanding the controversial Parkinson’s disease psychosis drug beyond the approved patient population.
Presenting at the Clinical Trials on Alzheimer’s Disease meeting — although they also enrolled patients with other types of dementia — Acadia investigators said Nuplazid (pimavanserin) reduced the risk of patients’ psychosis coming back by 2.8 fold. The hazard ratio was 0.353 for the primary endpoint, with a one-sided p-value of 0.0023.
“The magnitude of effect was strong for the HR and p-value, as the primary endpoint p-value (p=0.0023) hit well below the bar for stopping the trial early (p=0.0033),” Marc Goodman of SVB Leerink wrote in a note.
On the secondary endpoint, Nuplazid was found to have reduced the risk of discontinuation for any reason by 2.2 fold (HR=0.452, one-sided p=0.0024).
The results add up to an important advance for the 8 million patients with dementia in the US, up to 30% of whom can develop psychosis, according to trial leader Jeffrey Cummings.
“Reducing the risk of relapse of psychotic symptoms by this magnitude is an important and meaningful outcome as these are serious events which could lead to poor patient outcomes and a significant increase in caregiver burden and distress,” said Cummings, who’s also the director emeritus of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, in a statement.
While the study, which enrolled 392 patients in total, was not powered to reach conclusions about individual subgroups, Goodman saw the data as good enough to cover a broad label. Notably, Acadia execs had originally intended to focus on Alzheimer’s disease psychosis but broadened the reach to dementia with Lewy bodies, Parkinson’s disease dementia, vascular dementia and frontotemporal dementia when they finally kicked off the study in 2017. And it’s paying off.
A meeting regarding an sNDA with FDA regulators — who had granted them breakthrough therapy designation for dementia-related psychosis — is in the works for the first half of 2020, said Acadia president Serge Stankovic.
There are currently no approved treatments for dementia-related psychosis, Goodman noted, and the antipsychotics typically prescribed off-label can have poor tolerability, negatively impact cognition, and cause movement disorders.
Observations throughout nine months of treatment — for patients who were on the drug both during the initial three-month open-label portion and the subsequent double-blind, placebo-controlled segment — suggested that Nuplazid didn’t have those common side effects.
Acadia reported that 61.8% of the patients who went through open-label treatment pre-randomization graduated to the second phase.
The safety profile was in line with the current Nuplazid label in PDP, and the Nuplazid arm was similar to the placebo arm on AEs (41.0% Nuplazid, 36.6% placebo) and discontinuations due to AEs (2.9% Nuplazid, 3.6% placebo). Management highlighted that <10% of patients were treated with the lower 20mg dose, demonstrating a favorable tolerability of the 34mg dose.