ACP-204 · program
Remlifanserin for Alzheimer's disease psychosis
- FDA Fast Track (Alzheimer'S Disease Psychosis; Granted 2026-07-20)
Indications for ACP-204: Alzheimer's disease psychosis · Phase 3 Lewy body dementia psychosis · Phase 2
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.
Development timeline
- UpcomingClinicalTrials.gov estimated primary completion of the full RADIANT master protocol (NCT06159673), which covers both Phase 3 confirmatory substudies: January 2028 (estimated study completion February 2028).
- UpcomingTopline results from the Phase 2 RADIANT substudy of remlifanserin (ACP-204) 30 mg and 60 mg vs placebo in Alzheimer's disease psychosis (primary endpoint: change from baseline in SAPS-H+D at Week 6), expected September–October 2026.↗
- First dated public confirmation that the program is in Phase 3: ACADIA stated that enrollment in the Phase 2 portion of RADIANT is complete, that topline is expected September–October 2026, and that screening and enrollment are underway in the Phase 3 studies. The same release announced FDA Fast Track designation for remlifanserin in ADP. ACADIA has not disclosed the exact date the Phase 3 substudies opened, so this date is an upper bound — the true transition is on or before 2026-07-20.↗
- 52-week open-label extension NCT06194799 (ACP-204-008) started, enrolling by invitation from the RADIANT substudies (752 subjects; primary outcome treatment-emergent adverse events). Registered on ClinicalTrials.gov as Phase 3, but it is a long-term safety extension rather than a confirmatory efficacy study, so it is not treated here as the Phase 3 advance.
- RADIANT master protocol NCT06159673 (ACP-204-006) started per ClinicalTrials.gov: a seamless Phase 2/Phase 3 program in Alzheimer's disease psychosis. ACADIA announced initiation of the Phase 2 substudy on 2023-11-27 (~318 patients, ACP-204 30 mg or 60 mg vs placebo, 6 weeks, primary endpoint change from baseline in SAPS-H+D at Week 6; two ~378-patient Phase 3 substudies planned with near-identical design).
Readouts
- January 2028AnticipatedRegistry resultsNCT06159673
ClinicalTrials.gov estimated primary completion of the full RADIANT master protocol (NCT06159673), which covers both Phase 3 confirmatory substudies: January 2028 (estimated study completion February 2028).
- September to October 2026AnticipatedTopline dataNCT06159673
Topline results from the Phase 2 RADIANT substudy of remlifanserin (ACP-204) 30 mg and 60 mg vs placebo in Alzheimer's disease psychosis (primary endpoint: change from baseline in SAPS-H+D at Week 6), expected September–October 2026. ↗
Clinical trials in Alzheimer's disease psychosis
NCT06194799ACP-204-008Phase 3Recruitingn=752
A 52-Week, Open-Label Extension Study of ACP-204 in Adults With Alzheimer's Disease Psychosis
NCT06159673ACP-204-006Phase 2/3Recruitingn=1074
A Master Protocol for Three Independent, Seamlessly Enrolling, Double-blind, Placebo-controlled Efficacy and Safety Studies of ACP-204 in Adults With Alzheimer's Disease Psychosis
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| Remlifanserin oral capsule (30 mg / 60 mg once daily) 30 mg or 60 mg PO once daily in the Phase 2/3 RADIANT master protocol (ACP-204-006) and the ACP-204-008 open-label extension (60 mg QD initial dose, then flexible 30 or 60 mg QD); 30 mg and 60 mg QD in the Phase 2 Lewy body dementia psychosis study NCT07029581. Phase 1: single ascending oral doses 10-180 mg; multiple ascending doses up to 60 mg (healthy elderly) and 120 mg (healthy adults) for 10 days; the food-effect study used a 60 mg oral capsule. | Oral | Once daily | t½ 19.8 h · Tmax 5.98 h |
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.
| Target | Action | Affinity |
|---|---|---|
| 5-HT2AprimaryHTR2A | Inverse agonist | —ⓘ |
| 5-HT2CHTR2C | Inverse agonist | —ⓘ |
← Full ACP-204 compound page (identity, identifiers, all indications)
Sources
- Acadia Pharmaceuticals Receives FDA Fast Track Designation for Remlifanserin in Alzheimer's Disease Psychosis (2026-07-20) — Fast Track is ADP-only; no designation for LBDP — ACADIA Pharmaceuticals Inc.
- Burstein ES, et al. Nonclinical characterization of ACP-204, a novel selective serotonin 5-HT2A receptor inverse agonist. J Pharmacol Exp Ther. 2026;393(6):104932 — Journal of Pharmacology and Experimental Therapeutics (ASPET) / PubMed
- Darwish M, et al. Effect of Food Consumption on the Pharmacokinetics of ACP-204, a Novel 5-HT2A Receptor Selective Antagonist/Inverse Agonist. Alzheimer's & Dementia. 2025 — Alzheimer's & Dementia (Wiley) via PubMed Central
- NCT06159673 (ACP-204-006) — A Master Protocol for Three Independent, Seamlessly Enrolling, Double-blind, Placebo-controlled Efficacy and Safety Studies of ACP-204 in Adults With Alzheimer's Disease Psychosis — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT06194799 (ACP-204-008) — A 52-Week, Open-Label Extension Study of ACP-204 in Adults With Alzheimer's Disease Psychosis — ClinicalTrials.gov (U.S. National Library of Medicine)