Acadia’s remlifanserin Phase 2 trial narrowly missed its primary endpoint but showed a nominally significant secondary result, supporting Phase 3 development.
Written By: Aasritha Thippavajjala, PharmD
Reviewed By: Pharmacally Editorial Team
Acadia Pharmaceuticals announced topline results from the Phase 2 portion of the RADIANT clinical trial program evaluating remlifanserin for hallucinations and delusions associated with Alzheimer’s disease psychosis (ADP). The 60 mg once-daily dose narrowly missed the primary endpoint of change in SAPS-H+D at week 6 (p=0.0603) but showed a nominally significant improvement on the key secondary CGI-S-ADP endpoint (p=0.0077).
Based on these findings, Acadia plans to continue its Phase 3 program with the 60 mg dose while removing the 30 mg arm. Detailed results are expected to be presented at the Clinical Trials on Alzheimer’s Disease (CTAD) conference in Boston on November 16–19, 2026.
Primary Endpoint Narrowly Missed
The primary endpoint was change from baseline at week 6 in the Scale for the Assessment of Positive Symptoms-Hallucinations and Delusions (SAPS-H+D). The 60 mg dose produced a −12.6 change compared with −10.4 for placebo, with a standardized effect size of 0.26 and p=0.0603.
The primary endpoint therefore was not met. However, the treatment difference between 60 mg remlifanserin and placebo increased through the six-week treatment period. The 30 mg dose showed minimal improvement compared with placebo across endpoints.
Endpoint | 60 mg Remlifanserin | Placebo | Standardized Effect Size | P-Value / Status |
Primary: SAPS-H+D change from baseline at Week 6 | −12.6 | −10.4 | 0.26 | p=0.0603; primary endpoint not met |
Key secondary: CGI-S-ADP change from baseline at Week 6 | −1.3 | −0.9 | 0.37 | nominal p=0.0077; nominally significant |
Key Secondary Endpoint Shows Nominal Significance
On the Clinical Global Impression-Severity scale for ADP (CGI-S-ADP), the 60 mg group showed a −1.3 change from baseline versus −0.9 for placebo. The standardized effect size was 0.37, with a nominal p-value of 0.0077.
Because the supplied topline results do not describe the statistical testing hierarchy or adjustment for multiple comparisons, the nominal secondary-endpoint finding should be interpreted cautiously and does not establish confirmatory efficacy. All analyses were performed in the prespecified modified full analysis set (mFAS1) population.
Favorable Safety Profile
Remlifanserin showed a favorable topline safety and tolerability profile across both doses. Rates of adverse events, serious adverse events, and discontinuations due to adverse events were similar to placebo.
Acadia reported no signal of QT prolongation versus placebo and no deaths in the remlifanserin treatment arms. The dataset also suggested no negative impact on motor symptoms or cognition, although these topline findings do not establish the absence of such risks.
Phase 3 Program to Continue at 60 mg
Acadia plans to continue enrollment in its two ongoing Phase 3 studies in ADP while amending the program to remove the 30 mg dose arm. The source does not specifically state that the 30 mg efficacy findings were the reason for this decision.
Jeffrey Cummings, M.D., Sc.D., director of the Chambers-Grundy Center for Transformative Neuroscience at the University of Nevada, Las Vegas, said the findings provide encouraging evidence that 60 mg once-daily remlifanserin may reduce hallucinations and delusions in patients with Alzheimer’s disease. He highlighted the need for an efficacious, well-tolerated and convenient treatment compatible with the multiple concomitant medications commonly used by these patients. He also described the absence of observed negative effects on motor symptoms and cognition as encouraging.
RADIANT and Next Steps
RADIANT is a global, multicenter, randomized, double-blind, placebo-controlled, operationally seamless Phase 2/3 program. The Phase 2 portion evaluated 60 mg and 30 mg once-daily remlifanserin against placebo, with an option for participants to enter a long-term open-label extension.
Remlifanserin is a novel, highly selective 5-HT2A receptor inverse agonist being developed for ADP and Lewy body dementia psychosis. A separate Phase 2 study is evaluating its efficacy, safety and tolerability in Lewy body dementia psychosis.
Acadia plans to present detailed Phase 2 safety and efficacy results at CTAD in Boston on November 16–19, 2026. The detailed dataset will provide further information on the consistency and magnitude of the observed efficacy signals and the safety profile of the 60 mg dose.
Reference
Acadia Pharmaceuticals Announces Phase 3 Enabling Topline Results from Phase 2 RADIANT Study of Remlifanserin for the Treatment of Alzheimer’s Disease Psychosis (ADP), Acadia Pharmaceuticals, 24 September 2026
ACP-204 in Adults with Alzheimer’s Disease Psychosis, ClinicalTrials.gov ID NCT06159673
About the Writer
Aasritha Thippavajjala (Linkedin) is a pharm D student and aspiring medical writer with medical writing, clinical training experience and a strong interest in clinical research and patient safety She has hands-on exposure to clinical pharmacy activities including medication profile assessment, clinical case review, identification of potential drug-related problems, ADR awareness, patient counselling, and clinical documentation. She has also gained experience in medical literature review, evidence synthesis, and scientific communication through her published review article on digital twin-based patient simulation and her poster presentation at the 74th Indian Pharmaceutical Congress. Certified in ICH Good Clinical Practice (E6(R3)) and Scientific Writing in Health Research, she is passionate about applying her clinical knowledge and research skills to medical writing ,clinical research and contributing to accurate, evidence-based healthcare.