BioVie (BIVI) Study result summary

Study design and objectives

• SUNRISE-PD was a multicenter, randomized, double-blind, placebo-controlled phase II trial in early-stage Parkinson's disease, enrolling 57 patients naïve to dopaminergic therapy.

• The three-month, signal-finding study aimed to inform phase III design, focusing on both motor and non-motor endpoints and identifying responsive patient populations.

• Evaluated clinical scales (EPNIC-15, MDS-UPDRS Parts I-III, PDQ-39, PDSS-2) and a broad panel of 380 plasma biomarkers, including neurodegeneration and inflammation markers.

• Primary endpoint was impact on inflammation; secondary endpoints included neuronal injury, clinical outcomes, safety, and exploratory biomarkers.

• Hybrid decentralized design allowed participation from home or clinic, reducing barriers to enrollment.

Key efficacy and biomarker findings

• Bezisterim showed statistically significant improvements over placebo in both motor and non-motor symptoms, especially in patients with higher baseline inflammation.

• 283 of 380 proteins (74.5%) shifted toward a profile suggesting slowed disease progression; neurodegeneration and inflammation biomarkers improved.

• EPNIC-15 composite showed a large effect size (Cohen's d = -0.94, p = 0.0006), with 25% of treated patients meaningfully improving versus 6% on placebo.

• Statistically significant improvements were observed in neuroinflammation and systemic inflammation biomarkers, including CCL2, CHI3L1, IL-17A, IL-6, IFN-γ, and TNF-α.

• Bezisterim reduced neurodegeneration biomarkers (NfL, GFAP) and improved blood-based inflammatory markers.

Mechanistic insights and clinical impact

• Bezisterim is believed to block ERK/NFκB-mediated inflammatory signaling while preserving homeostatic function.

• Treatment led to reduced CCL2 expression, lower monocyte recruitment, and decreased monocyte-to-lymphocyte ratio, indicating reduced systemic inflammation.

• Mechanistic data support bezisterim's action on neuroinflammation and insulin resistance pathways.

• Amyloid beta and p-tau, Alzheimer's biomarkers, also trended positively.

• Clinical impact was observed on both motor and non-motor symptoms, with potential for disease modification.