Remlifanserin

Mechanism of action

Potent, highly selective inverse agonist and functional antagonist at the serotonin 5-HT2A receptor (HTR2A), a Gq-coupled class-A GPCR. Nonclinical characterization reports subnanomolar affinity in 5-HT2A radioligand binding and subnanomolar inverse-agonist and antagonist potency in cell-based functional assays, with 13-fold lower affinity for 5-HT2C in binding and 30- to 100-fold lower potency at 5-HT2C in functional assays, and >1000-fold selectivity against more than 70 other targets. No appreciable agonist activity was seen at 5-HT1A/1B/1D/1E/1F, 5-HT2B, 5-HT7, alpha-1A/alpha-2A/2B/2C adrenergic, D1, D2, H1, or M1-M5 muscarinic receptors. Compared with pimavanserin it has 9-fold lower hERG inhibitory potency and lower potency at Cav1.2 and Nav1.5. It was orally active in three rodent models of schizophrenia and engaged central 5-HT2A receptors in non-human primates. The clinical hypothesis is that selective 5-HT2A inverse agonism reduces hallucinations and delusions by restoring excitatory/inhibitory balance without direct dopamine D2 blockade.

Formulations

Remlifanserin for Alzheimer's disease psychosis

Phase 3ActiveAlzheimer's disease psychosis indication →

Remlifanserin (ACP-204), a potent and highly selective serotonin 5-HT2A receptor inverse agonist, for hallucinations and delusions associated with Alzheimer's disease psychosis (ADP). This is ACADIA's lead ACP-204 indication and the follow-on to its marketed 5-HT2A inverse agonist pimavanserin (NUPLAZID, approved for Parkinson's disease psychosis). Development runs under the RADIANT master protocol (NCT06159673, ACP-204-006): three independent, seamlessly enrolling, double-blind, placebo-controlled studies — one Phase 2 dose-ranging substudy plus two near-identical Phase 3 confirmatory substudies — all testing ACP-204 30 mg and 60 mg once daily against placebo over 6 weeks with a primary endpoint of change from baseline in SAPS-H+D total score. Total registered enrollment across the master protocol is 1,074; the Phase 2 substudy was approximately 318 patients and each Phase 3 substudy approximately 378. Completers may roll into a 52-week open-label extension (NCT06194799, ACP-204-008, 752 subjects). As of 2026-07-20 ACADIA reported that Phase 2 enrollment is complete with topline expected September–October 2026, and that screening and enrollment are underway in the Phase 3 studies. FDA granted Fast Track designation for ADP on 2026-07-20. No dose-arm drops, protocol discontinuations or safety holds are publicly disclosed; both the 30 mg and 60 mg arms remain in the ClinicalTrials.gov record as of its 2026-07-24 update.

Remlifanserin for Lewy body dementia psychosis

Phase 2RecruitingLewy body dementia psychosis indication →

Remlifanserin (ACP-204) for psychosis associated with Lewy body dementia (LBDP — a term that as used by the sponsor and the registry encompasses dementia with Lewy bodies and Parkinson's disease dementia), the second indication for ACADIA's selective 5-HT2A inverse agonist. ACADIA guided at its inaugural R&D Day (2025-06-25) to a Phase 2 LBDP start in Q3 2025; the study, NCT07029581 (ACP-204-012), 'A Double-Blind, Placebo-Controlled, Phase 2, Efficacy and Safety Study of ACP-204 in Adults With Lewy Body Dementia Psychosis', started 2025-08-06 and is recruiting: approximately 180 adults aged 55–85, ACP-204 30 mg or 60 mg vs placebo over 6 weeks, primary endpoint change from baseline in SAPS-LBDP total score at Week 6. A 52-week open-label extension, NCT07095465 (ACP-204-013, 126 subjects, enrolling by invitation), started 2025-11-14; it is registered on ClinicalTrials.gov as Phase 3 but is a long-term safety extension, not a confirmatory efficacy study, so the program is recorded as Phase 2 — consistent with ACADIA's own pipeline page. No FDA designations have been announced for LBDP (the 2026-07-20 Fast Track applies to Alzheimer's disease psychosis only), and no company topline date has been guided.

Clinical trials