SUNRISE-PD
Phase 2b Randomized, Double-Blind, Placebo-Controlled Study of Bezisterim in Early, Levodopa-Naïve Parkinson's Disease (SUNRISE-PD)
Clinical Question
In early, levodopa-naïve Parkinson's disease, does the oral anti-inflammatory bezisterim reduce systemic inflammation and improve clinical outcomes versus placebo?
Study Overview
Objective
Evaluate whether bezisterim reduces systemic/neuro-inflammation and improves motor and non-motor measures in early, levodopa-naïve Parkinson's disease.
Study Summary
- Phase 2b, randomized 1:1, double-blind, placebo-controlled; 57 levodopa-naïve early-PD patients; bezisterim 20 mg BID vs placebo × 12 weeks.
- PRIMARY endpoint was PHARMACODYNAMIC (hematologic inflammatory indices — NLR, MLR, SIRI, SII, PLR, AISI + composite) and was MET — i.e., an anti-inflammatory mechanism readout, not a clinical-efficacy endpoint.
- Exploratory clinical composite EPNIC-15 favored bezisterim (−0.04 vs +0.18; Cohen's d −0.94; p=0.0006); MDS-UPDRS Parts I–III improved, most in the ~50% with baseline platelets >230×10³/µL.
- Neurofilament light (NfL) rise slowed (p=0.008); Aβ42 (p=0.09) and pTau-217 (p=0.13) only trends; broad anti-inflammatory proteomic shift (283/380 proteins).
- Well tolerated — AEs 39.3% vs 51.7% placebo, no serious AEs. A platelet-enriched, potentially pivotal Phase 3 is planned. ⚠ Company topline press release — not peer-reviewed.
Intervention
Bezisterim 20 mg orally twice daily vs matching placebo for 12 weeks.
Patients per Arm
57 total, randomized 1:1
Bottom Line
Bezisterim met its pharmacodynamic (anti-inflammatory biomarker) primary endpoint and showed exploratory clinical and neurodegeneration-biomarker signals (EPNIC-15 p=0.0006; slowed NfL p=0.008) in early levodopa-naïve PD, with placebo-like tolerability. Encouraging but early: clinical efficacy is exploratory in a small 12-week study, and the responder finding (platelets >230k) is a post-hoc enrichment. Topline press-release data.
Major Points
- Primary endpoint was an inflammatory-biomarker (pharmacodynamic) composite — MET; clinical outcomes were secondary/exploratory.
- EPNIC-15 exploratory clinical composite favored bezisterim (Cohen's d −0.94, p=0.0006).
- MDS-UPDRS Parts I, II, III improved, most in the ~50% with baseline platelets >230×10³/µL.
- NfL rise slowed (−0.0148 vs +0.0095 log2/week; p=0.008); Aβ42 and pTau-217 only trends.
- Safety comparable to placebo (AEs 39.3% vs 51.7%; no SAEs). Phase 3 with platelet enrichment planned.
Design
Study Type: Phase 2b, randomized, double-blind, placebo-controlled
Randomization: 1:1
Blinding: Double-blind, matching placebo
Treatment Duration: 12 weeks (20-week total program)
Setting: Multicenter, hybrid decentralized
Inclusion Criteria
- Early-stage Parkinson's disease
- Naïve to carbidopa/levodopa
Arms
| Field | Bezisterim | Placebo |
|---|---|---|
| Intervention | Bezisterim 20 mg orally twice daily × 12 weeks | Matching placebo × 12 weeks |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Change in hematologic inflammatory indices (NLR, MLR, SIRI, SII, PLR, AISI) and composite | Primary | Met prespecified endpoints | |||
| EPNIC-15 clinical composite | Secondary | Bezisterim −0.04 vs placebo +0.18; Cohen's d −0.94; p=0.0006 | |||
| MDS-UPDRS Parts I–III | Secondary | Significant improvement; greatest in baseline platelets >230×10³/µL (~50%) | |||
| Neuroinflammation composite | Secondary | −0.28 vs +0.19; Cohen's d −1.06; p=0.0018 | |||
| NfL (neurodegeneration) | Secondary | −0.0148 vs +0.0095 log2/week; Cohen's d −0.746; p=0.008 | |||
| Aβ42 / pTau-217 | Secondary | Favorable trends only (p=0.088 / p=0.127) | |||
Criticisms
- Primary endpoint was a pharmacodynamic biomarker, not a clinical outcome.
- Small sample (n=57) and short (12-week) duration.
- Clinical benefits (EPNIC-15, MDS-UPDRS) were secondary/exploratory; EPNIC-15 is a novel composite.
- High-platelet responder subgroup is a post-hoc enrichment signal.
- Company topline press release — not peer-reviewed; full data pending.
Funding
BioVie Inc.
Based on: SUNRISE-PD (Company press release (topline; not yet peer-reviewed), 2026)
Authors: BioVie Inc. (sponsor) — topline results
Citation: BioVie Inc. Topline Results of Phase 2 SUNRISE-PD Trial of Bezisterim in Early Parkinson's Disease. Press release, 2026.
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