Bezisterim Shows Improvements in Motor, Nonmotor Symptoms in Phase 2 SUNRISE-PD Trial

BioVie has announced positive topline results from its phase 2 SUNRISE-PD trial (NCT06757010) evaluating the investigational therapy bezisterim in patients with early Parkinson disease (PD), with findings showing statistically significant improvements in both motor and nonmotor symptoms alongside favorable effects on multiple inflammatory and neurodegeneration biomarkers.¹

According to the company, bezisterim met its predefined study objectives, demonstrating improvements in inflammatory biomarkers together with favorable changes across a range of exploratory clinical and biological measures. Patients receiving bezisterim experienced greater improvements than placebo-treated participants across multiple measures of daily functioning, motor symptoms, and nonmotor manifestations of disease.

"The topline results of the SUNRISE-PD trial are encouraging and demonstrate the potential for bezisterim to address significant unmet clinical needs in Parkinson disease through a differentiated therapeutic approach that targets the underlying disease biology rather than focusing solely on symptomatic treatment provided by currently approved therapies," Cuong Do, president and chief executive officer of BioVie, said in a statement.¹

Clinical Findings

As previously reported by NeurologyLive, the randomized, double-blind, placebo-controlled proof-of-concept phase 2 study enrolled 57 patients with early-stage PD who had not previously received carbidopa/levodopa therapy. Conducted over 12 weeks, the trial was designed to evaluate the effects of bezisterim on blood-based inflammatory biomarkers while also assessing motor function, nonmotor symptoms, quality of life, and safety to help inform the design of a potential registrational phase 3 study.

The study's primary clinical endpoint centered on the exploratory EPNIC-15 composite score, which incorporates 15 clinically relevant assessments drawn from the Movement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) Parts I through III as well as the Parkinson Disease Sleep Scale-2.

Patients treated with bezisterim demonstrated significantly greater improvement than placebo on the composite endpoint, with mean changes of -0.04 versus +0.18, respectively (Cohen d = -0.94; P = .0006). Investigators also reported statistically significant improvements across MDS-UPDRS Parts I, II, and III, reflecting benefits in nonmotor symptoms, activities of daily living, and motor function.

Exploratory subgroup analyses suggested treatment effects were greatest among patients with higher baseline platelet counts, a biomarker associated with systemic inflammation. Among participants with platelet counts exceeding 230 × 10³/µL, approximately half of the enrolled population, bezisterim demonstrated statistically significant advantages over placebo across every evaluated clinical outcome, including the EPNIC-15 composite and MDS-UPDRS Parts I, II, III, and total scores.

Although treatment effects appeared more pronounced in patients with higher inflammatory status, investigators noted that clinical improvements were observed across the broader study population.

"The improvement across both motor and nonmotor domains of the MDS-UPDRS is encouraging because these measures represent clinically meaningful outcomes recognized by physicians, patients, and the FDA," Mark Stacy, MD, William E. Murray Professor of Neurology at the Medical University of South Carolina, said in a statement.¹ "The finding that treatment effects were greater in patients with higher platelet levels supports the rationale that reduction in neuronal inflammation remains an unmet need in neurodegenerative disease."

Biomarker and Proteomic Findings

In addition to clinical improvements, bezisterim was associated with statistically significant reductions in several biomarkers linked to neuroinflammation and systemic inflammation.

The composite neuroinflammatory measure favoredbezisterim over placebo (-0.28 vs +0.19; Cohen d = -1.06; P = .0018), with improvements observed across biomarkers including CCL2, CHI3L1, and VGF, as well as systemic inflammatory markers such as IL-6, IL-17A, TNF-α, interferon-γ, the monocyte-to-lymphocyte ratio, and the Systemic Inflammation Response Index.

Proteomic analyses demonstrated broad biological effects, with 283 of 380 measured proteins shifting toward a profile associated with lower inflammatory burden (binomial P = 3.2 × 10⁻²²). The company reported that this pattern aligned with previous proteomic studies linking inflammatory signatures with PD progression.

Investigators also observed favorable changes in exploratory biomarkers associated with neurodegeneration. Between weeks 4 and 12, treatment with bezisterim was associated with reductions in composite neuronal injury markers compared with placebo (Cohen d = -0.57; P = .043).

Significant reductions in neurofilament light chain (NfL) were also reported during this period (P = .008), while favorable directional changes were noted for glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCHL1), MAPT, amyloid-β42, and phosphorylated tau 217. The company emphasized that these biomarker findings remain exploratory and require confirmation in larger clinical studies.

Safety Profile

Bezisterim was generally well tolerated throughout the 12-week study. Treatment-emergent adverse events (AEs) occurred in 39.3% of patients receiving bezisterim compared with 51.7% of those receiving placebo. No severe or serious AEs were reported, and each treatment arm experienced one treatment-related adverse event. Most reported AEs were mild in severity.

Joseph M. Palumbo, MD, chief medical officer at BioVie, said the findings provide support for advancing the program into later-stage development. "We are encouraged by the clinical, biomarker, proteomic, and safety findings observed in this focused study of 57 patients over 12 weeks of treatment and look forward to presenting these results at an upcoming medical meeting," Palumbo said in a statement.¹ "These exploratory findings strengthen our confidence in bezisterim's potential to address the broad symptomatic burden of Parkinson disease and will inform the design of a future potentially registrational study."

REFERENCES
1. BioVie Announces Topline Results of Phase 2 SUNRISE-PD Trial of Bezisterim in Early Parkinson’s Disease. BioVie. News Release. August 6, 2026. Accessed: August 6, 2026. https://investors.bioviepharma.com/news/news-details/2026/BioVie-Announces-Topline-Results-of-Phase-2-SUNRISE-PD-Trial-of-Bezisterim-in-Early-Parkinsons-Disease/default.aspx