While Acadia Pharmaceuticals’ candidate has missed the main goal of a Phase 2 trial, the company is still moving forward with the anti-psychosis candidate in Alzheimer’s disease as well as Lewy body dementia.
Acadia Pharmaceuticals’ investigational Alzheimer’s disease psychosis asset did not significantly improve hallucinations and delusions—a result the biotech called a narrow miss—but will move forward anyway on the strength of secondary endpoint results.
“This is a highly Phase 3–enabling set of data,” Acadia CEO Catherine Owen Adams said on a Thursday investor call reviewing the data.
The ongoing RADIANT Phase 2/3 trial is evaluating remlifanserin, a 5HT2A receptor inverse agonist, for hallucinations and delusions associated with Alzheimer’s disease psychosis (ADP).
In the Phase 2 portion of the trial, remlifanserin failed to significantly improve hallucinations and delusions, as measured by an industry scale. The biopharma said the outcome on the study’s higher 60-mg dose “narrowly missed,” with a 12.6-point drop recorded compared to a 10.4 reduction for placebo. Acadia touted the p-value of 0.0603 for the result as close to the desired p-value of 0.05 or less.
The company also pointed to a secondary endpoint of a clinician-rated severity scale for ADP; on this measure, remlifanserin achieved statistical significance for the 60-mg cohort. A 30-mg dose was also tested and showed “minimal improvement across endpoints compared to placebo,” according to Acadia.
Given the findings, the San Diego biopharma plans to remove the 30-mg dosage arm from the ongoing Phase 3 RADIANT program. When asked on the call if Acadia plans to change the primary endpoint in the late-stage trial, Owen Adams said, “at this point, we’re not proposing that.”
Analysts expect Acadia’s stock to take some hit from today’s readout but weren’t entirely bearish on the continued prospects of the drug. As of market open, Acadia’s stock slid nearly 10%, resting at $23 per share.
This “is definitely not the worst case outcome,” Stifel analysts wrote Thursday, citing the actions Acadia can take, such as dropping the low dose, to increase the study’s power.
“But for us, there isn’t a path to conviction here,” Stifel continued, adding that ADP is a tough condition and the Phase 3 findings are still a ways off.
BMO analysts said “some encouraging signals” support future development of remlifanserin, citing the “nearly significant benefit” on the primary endpoint combined with significant improvement on the secondary endpoint.
Owen Adams underscored significant unmet need for patients with ADP. More than 7 million Americans currently live with Alzheimer’s disease and about 30% of those patients experience psychosis. This July, remlifanserin secured Fast Track status from the FDA in this indication.
Remlifanserin demonstrated a favorable safety profile, with rates of adverse events similar to that of placebo. No signals of QT prolongation—a delay in the heart’s electrical reset after each beat—or motor symptoms were observed, which reads positively for the future development of the asset in the separate indication of psychosis associated with Lewy body dementia (DLB), according to BMO.
Acadia is continuing remlifanserin’s mid-stage development in this indication, a progressive brain disorder caused by a buildup of protein in the brain. The Phase 2 trial is expected to read out in early 2028, according to ClinicalTrials.gov.
“This indication is high risk because there is very little clinical trial precedent in DLB, but it is a disease where the mechanistic rationale of 5HT2a inverse agonism/antagonism is, at least on a theoretical level, stronger, making this an interesting catalyst for the stock,” Stifel wrote.
