Acadia Advances Phase 3
Acadia Plans Phase 3 Trial for Alzheimer’s Drug Despite Missing Primary Endpoint
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Key Points
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The 60 mg dose reduced SAPS H+D scores by 12.6 points, compared with 10.4 points for placebo, for an effect size of 0.26 and a p-value of 0.0603. On the secondary measure of overall psychosis severity, the effect size was 0.37 with a nominal p-value of 0.0077.
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An analysis using somewhat higher baseline psychosis criteria retained about 80% of Phase 2 participants and increased the primary-endpoint effect size from 0.26 to 0.33, a potential basis for refining Phase 3 enrollment criteria.
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The indication has no FDA-approved therapy specifically for hallucinations and delusions associated with Alzheimer’s disease psychosis. Bristol Myers Squibb is testing COBENFY in three Phase 3 ADEPT studies; ADEPT-2 is expected to enroll about 500 patients, compared with 326 in Acadia’s RADIANT analysis.
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Acadia is also evaluating remlifanserin in a separate Phase 2 study for psychosis associated with Lewy body dementia.
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The reported safety findings included adverse events, serious adverse events and discontinuations at rates similar to placebo, with no QT signal, deaths, or observed worsening of motor function or cognition.
Acadia Pharmaceuticals' stock plunged 19% after its Phase 2 RADIANT trial of remlifanserin narrowly missed the primary goal for treating psychosis in Alzheimer's patients. The 60 mg dose reduced hallucinations and delusions by 12.6 points versus 10.4 for placebo—a gap that wasn't statistically significant at p=0.0603—but a secondary measure showed nominal improvement. Goldman Sachs cut the stock to sell with a $17 price target.
Despite the miss, Acadia plans to advance the 60 mg dose into Phase 3, potentially with tighter enrollment criteria that could boost efficacy. The company will likely drop the 30 mg dose, which showed no improvement over placebo. Safety data looked solid—adverse events matched placebo with no deaths, QT issues, or cognitive decline. Full results come at the CTAD conference in November 2026.
How Remlifanserin Almost Won—But Didn't
The RADIANT trial enrolled 326 patients with Alzheimer's-related psychosis. The 60 mg dose cut SAPS H+D scores (a standard measure of hallucinations and delusions) by 12.6 points against 10.4 for placebo. The effect size was 0.26—a modest difference. The p-value of 0.0603 fell just short of the 0.05 threshold needed for statistical significance.
However, a secondary endpoint showed promise. Overall psychosis severity improved with an effect size of 0.37 and p-value of 0.0077—both nominally significant. This mixed result left analysts divided on whether the trial truly failed or came close enough to justify moving forward.
A Phase 3 Path With Tighter Patient Selection
Acadia identified a potential fix: screening for higher baseline psychosis severity. When analysts re-ran data on patients meeting stricter entry criteria, the primary effect size jumped from 0.26 to 0.33 while retaining 80% of the study population. This tweak could improve Phase 3 odds without excluding too many patients.
The company will likely use this refined approach in Phase 3. Dropping the 30 mg dose makes sense—it showed no edge over placebo. Phase 3 enrollment could run larger than RADIANT's 326 patients, especially given competition from Bristol Myers Squibb's COBENFY, which is in three Phase 3 ADEPT trials with about 500 patients in ADEPT-2 alone.
No Safety Red Flags—A Silver Lining
Remlifanserin's safety profile was clean. Adverse events, serious adverse events, and discontinuation rates all matched placebo. No deaths occurred. No QT prolongation—a heart-rhythm signal—was detected. Motor function and cognition stayed stable in both groups.
This favorable safety data is crucial. Goldman Sachs and other skeptics cite efficacy risk, not safety concerns, as the reason for caution. A Phase 3 success in this unmet market could still be valuable—no FDA-approved drug treats Alzheimer's-related psychosis specifically.
Broader Pipeline and Lewy Body Opportunity
Beyond Alzheimer's, Acadia is testing remlifanserin in a separate Phase 2 study for psychosis linked to Lewy body dementia. Success there could diversify the pipeline and reduce dependence on Phase 3 Alzheimer's results. Lewy body dementia patients often have severe hallucinations, making the indication potentially attractive.
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