Small Molecule · RP5063

Brilaroxazine (RP5063)

Phase 3Reviva Pharmaceuticals Holdings, Inc. (RVPH)

Oral, once-daily small-molecule multimodal serotonin-dopamine modulator ('stabilizer') in development for schizophrenia and other neuropsychiatric disorders. Acts as a partial agonist at dopamine D2/D3/D4 and serotonin 5-HT1A/5-HT2A receptors and an antagonist at 5-HT2B/5-HT6/5-HT7 (with moderate 5-HT2C affinity and serotonin-transporter activity), a profile intended to balance positive, negative and affective symptoms with low EPS/metabolic/prolactin liability. Developed by Reviva Pharmaceuticals; the pivotal Phase 3 RECOVER trial met its primary endpoint, and the FDA has requested a confirmatory second Phase 3 (RECOVER-2) before NDA submission.

Also known as: RP5063, RP-5063, brilaroxazine, oxaripiprazole, 1239729-06-6, 6-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy]-4H-1,4-benzoxazin-3-one

Data current as of

Modality
Small molecule
Chemical class
benzoxazinone, arylpiperazine, dichlorophenylpiperazine
Chemistry
Achiral
Mechanism
D2 Partial agonist
Highest phase
Phase 3
Lead indication
Schizophrenia
Developer
Reviva Pharmaceuticals Holdings, Inc. (RVPH)
Trials
3 tracked · 18 sites
Next catalyst
1H 2026 start (topline thereafter) — Topline data (Schizophrenia)

Mechanism of action

Multimodal dopamine-serotonin 'stabilizer'. Partial agonist at dopamine D2 (high affinity), D3 and D4 and at serotonin 5-HT1A and 5-HT2A receptors; antagonist at 5-HT2B, 5-HT6 and 5-HT7 (with moderate 5-HT2C affinity and serotonin-transporter activity). The combination of D2/D3 partial agonism, 5-HT1A partial agonism and 5-HT2A/2B/7 antagonism is hypothesized to address positive, negative and affective symptoms of schizophrenia while limiting EPS, weight gain, metabolic effects and prolactin elevation. Functional actions per Cantillon et al. 2018 (Clin Transl Sci); numeric Ki values tabulated in secondary compilations citing Cantillon/Rajagopal 2017.

TargetActionAffinity
D2primaryDRD2Partial agonistKi 0.37 nMⓘ
5-HT1AHTR1APartial agonistKi 1.5 nMⓘ
5-HT2AHTR2APartial agonistKi 2.5 nMⓘ
5-HT2BHTR2BAntagonistKi 0.19 nMⓘ
5-HT7HTR7AntagonistKi 2.7 nMⓘ
D3DRD3Partial agonistKi 3.7 nMⓘ
D4DRD4Partial agonistKi 6 nMⓘ

Formulations

FormulationRouteRegimenPharmacokinetics
Brilaroxazine oral tablet
15, 30, or 50 mg once daily (Phase 3 RECOVER)
OralOnce dailyt½ 55 h · Tmax 5 h · F 80%

Development timeline

Phase 3Jan 2022 – Jun 2026
  1. UpcomingpendingRECOVER-2 confirmatory Phase 3 planned to initiate in 1H 2026.↗
  2. pendingFDA recommends a confirmatory second Phase 3 (RECOVER-2) before a brilaroxazine schizophrenia NDA.↗
  3. metFull 1-year RECOVER open-label extension positive: durable, dose-related efficacy with favorable long-term safety.↗
  4. Reviva reported FDA alignment on the brilaroxazine schizophrenia NDA path: two positive Phase 3 efficacy studies at Week 4 plus >=12 months of long-term safety data could support an NDA for acute treatment of schizophrenia.↗
  5. metPhase 3 RECOVER met its primary endpoint: brilaroxazine 50 mg cut PANSS total by 10.1 points vs placebo at Week 4 (p<0.001).↗
  6. Pivotal Phase 3 RECOVER trial (NCT05184335) started: 28-day randomized, double-blind, placebo-controlled study of brilaroxazine 15 mg and 50 mg vs placebo in acute schizophrenia, followed by a 52-week open-label extension.

Brilaroxazine (RP5063) for Schizophrenia

Phase 3ActiveSchizophrenia indication →

Lead program. The global pivotal Phase 3 RECOVER trial (NCT05184335; 28-day double-blind, placebo-controlled, plus a 52-week open-label extension) MET its primary endpoint at the 50 mg dose: PANSS total -10.1 vs placebo at Week 4 (brilaroxazine -23.9 vs placebo -13.8; Cohen's d 0.6; p<0.001), topline reported 30 Oct 2023. The 1-year OLE was positive with a favorable safety/tolerability profile (full dataset 2 Jun 2025). On 15 Apr 2024 Reviva reported FDA alignment that two positive Phase 3 efficacy studies at Week 4 plus >=12 months of safety data could support an NDA; a 23 Dec 2025 regulatory update confirmed the FDA recommended a second Phase 3 (RECOVER-2; global, ~450 patients, 30 mg and 50 mg, 4-week) to be initiated in 1H 2026 subject to financing. Program remains active in Phase 3; not yet filed.

Readouts

  • 1H 2026 start (topline thereafter)AnticipatedTopline datapending

    RECOVER-2 confirmatory Phase 3 planned to initiate in 1H 2026. ↗

  • 2025-12-23ReportedRegulatorypending

    FDA recommends a confirmatory second Phase 3 (RECOVER-2) before a brilaroxazine schizophrenia NDA. ↗

  • 2025-06-02ReportedFull resultsmetNCT05184335

    Full 1-year RECOVER open-label extension positive: durable, dose-related efficacy with favorable long-term safety. ↗

  • 2023-10-30ReportedTopline datametNCT05184335

    Phase 3 RECOVER met its primary endpoint: brilaroxazine 50 mg cut PANSS total by 10.1 points vs placebo at Week 4 (p<0.001). ↗

Clinical trials

NCT05184335RVP-30-001 (RECOVER)Phase 3Completedn=412

Phase 3, Randomized, 28 Days, Double-blind, Placebo-controlled, Multicenter Study to Assess the Safety and Efficacy of Brilaroxazine (RP5063) in Subjects With Schizophrenia, Followed by a 52-Week Open-label Extension

Started Jan 2022· Primary completion Sept 2023· 📍 18 sites across 1 country (United States)

metprimaryPANSS total score change from baseline to Week 4 (Day 28), 50 mg vs placebo — LSMD -10.1 (brilaroxazine 50 mg -23.9 vs placebo -13.8; Cohen's d 0.6) (<0.001)

Primary endpoint met at the 50 mg dose; the 15 mg dose was numerically superior to placebo but not statistically significant. ~412 patients randomized to 15 mg, 50 mg or placebo once daily for 28 days.

metsecondaryCGI-S change from baseline to Week 4, 50 mg vs placebo — ~1-point improvement (Cohen's d 0.5) (<0.001)

Key secondary endpoint met; positive symptoms -2.8 (d 0.5, p<0.001) and negative symptoms -2.0 (d 0.4, p=0.003) also improved vs placebo at 50 mg.

metsecondary52-week open-label extension: PANSS total change and long-term safety/tolerability — Pooled ~-18 point PANSS improvement at 12 months; ~1.5 kg mean weight change (<0.001)

1-year OLE positive: durable, dose-related symptom improvement (15/30/50 mg) with low TEAE burden, minimal akathisia/EPS and a favorable metabolic profile. Full dataset reported 2 Jun 2025.

Phase 3Activen=450

RECOVER-2: A Global, Randomized, Double-blind, Placebo-controlled, Multicenter 4-Week Study to Assess the Safety and Efficacy of Brilaroxazine in Patients With Acute Schizophrenia

RECOVER-2Phase 3Activen=450

RECOVER-2: A Global, Randomized, Double-blind, Placebo-controlled, Multicenter 4-Week Study to Assess the Safety and Efficacy of Brilaroxazine in Patients With Acute Schizophrenia

Related compounds

Other D2 compounds

Identifiers

Sources

  1. Cantillon, Ings & Bhat 2018 — Initial Clinical Experience of RP5063 (brilaroxazine): multimodal D2/3/4 + 5-HT1A/2A/2B/7 receptor profile and functional actions — Clinical and Translational Science (PMC)
  2. Pharmacokinetics of RP5063 Following Single Doses to Normal Healthy Volunteers and Multiple Doses Over 10 Days to Stable Schizophrenic Patients — PubMed / NCBI
  3. Reviva Announces FDA Alignment on Brilaroxazine Clinical Trials for NDA in Schizophrenia (15 Apr 2024) — Reviva Pharmaceuticals / IR
  4. Reviva Announces Positive Full Dataset for 1-Year Phase 3 RECOVER Open-Label Extension Study Evaluating Brilaroxazine in Schizophrenia (2 Jun 2025) — Reviva Pharmaceuticals / IR
  5. Reviva Announces Positive Topline Results from Global Pivotal Phase 3 RECOVER Trial of Brilaroxazine in Schizophrenia (30 Oct 2023) — Reviva Pharmaceuticals / IR
  6. Reviva Announces Regulatory Update Regarding the Development of Brilaroxazine for the Treatment of Schizophrenia — FDA recommends second Phase 3 (RECOVER-2) (23 Dec 2025) — Reviva Pharmaceuticals / IR
  7. Safety and Efficacy of Brilaroxazine (RP5063) in Schizophrenia (oral once-daily 15/30/50 mg) — ClinicalTrials.gov