BioVie (NASDAQ:BIVI) said its Phase II SUNRISE-PD trial of bezisterim in Parkinson’s disease produced signals across clinical measures, inflammatory biomarkers and markers of neurodegeneration, findings the company plans to use in designing a Phase III program.
Bezisterim is an orally administered small molecule taken twice daily that crosses the blood-brain barrier, according to President and CEO Cuong Do. The company believes the drug may reduce inflammation by affecting ERK and NF-κB pathways and, in turn, TNF-α production. BioVie also said the mechanism may be relevant to insulin resistance and neurodegeneration.
Phase II Trial Findings
The study evaluated motor and non-motor Parkinson’s disease measures, including the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale, or MDS-UPDRS; sleep and quality-of-life measures; and a company-developed composite called the Early Parkinson’s Neuro-Inflammation Composite 15, or EPNIC-15.
Across the full study population, BioVie reported that patients receiving bezisterim showed smaller changes from baseline than placebo recipients on several clinical measures, though Do said those results did not achieve statistical significance. The company said a subgroup with higher baseline inflammation, defined in the presentation as platelet counts above 230, showed statistically significant advantages over placebo on MDS-UPDRS Parts I, II and III, the total score, and EPNIC-15.
Do said the higher-inflammation subgroup improved during the three-month treatment period on measures of non-motor symptoms, activities of daily living and motor function. He added that BioVie does not intend to exclude lower-platelet patients from a Phase III trial, but expects to enrich the trial population by enrolling a larger proportion of patients with higher inflammation levels.
“Enrichment simply means we over-enroll a population that we think the drug will work for,” Do said during the question-and-answer session.
Composite and Biomarker Results
BioVie said EPNIC-15 was designed to capture both motor and non-motor symptoms through 15 Parkinson’s disease domains. The company reported that 25% of bezisterim-treated patients meaningfully improved on the composite, compared with 6% of placebo patients. Meanwhile, BioVie said 14% of treated patients meaningfully worsened, compared with 46% of placebo patients.
The company also conducted a blood-plasma proteomic analysis of 380 proteins. According to Do, 283 proteins moved in what BioVie characterized as a beneficial direction. The company said seven Parkinson’s disease-related proteins, more than 90% of 36 neuronal-injury biomarkers, and more than 75% of over 150 inflammation-related biomarkers moved favorably.
BioVie highlighted neurofilament light chain, or NfL, and glial fibrillary acidic protein, or GFAP, as biomarkers associated with neurodegeneration. The company said NfL initially increased before declining in the bezisterim group, while placebo patients showed an increase in a composite of neurodegeneration biomarkers. Do said the findings suggest a potential effect on neurodegeneration but acknowledged that the company would need to test that hypothesis in a longer study.
Joseph Palumbo, BioVie’s chief medical officer, said the NfL findings were “extremely encouraging,” while emphasizing that whether bezisterim can slow disease progression remains a question for future trials.
Phase III Plans and Safety
BioVie said it plans to seek an end-of-Phase-II meeting with the FDA to discuss a Phase III design. Do outlined a potential two-part program consisting of a six-month symptomatic-treatment phase, likely using MDS-UPDRS Part III motor score as the primary endpoint, followed by an additional 12 months to assess whether the drug alters disease progression.
The company said it would also seek to include non-motor measures, such as MDS-UPDRS Parts I and II, sleep measures and potentially EPNIC-15, in the Phase III program. Mark Stacy, the William E. Murray Professor of Neurology at the Medical University of South Carolina, said a longer study should examine whether the active-treatment group shows a change in the disease-progression slope.
BioVie reported no serious adverse events, no severe events and no deaths in SUNRISE-PD. It said there were two treatment-related adverse events overall, one in the treatment arm and one in the placebo arm; the treatment-arm event was described as mild and did not cause the patient to discontinue the study.
Separately, Do said BioVie expects data from its long-COVID trial within 30 to 60 days, if development proceeds as planned. The company said it will continue analyzing the Parkinson’s data, prepare scientific presentations and publications, and resume partnering discussions.
About BioVie (NASDAQ:BIVI)
BioVie Inc is a clinical‐stage biopharmaceutical company focused on developing novel therapies for chronic liver diseases and associated neurological complications. The company’s research and development efforts center on candidates designed to address serious unmet medical needs in hepatic encephalopathy and other liver‐related disorders. BioVie advances its pipeline through controlled clinical trials and regulatory interactions in North America.
The company’s lead product candidate, BIV201, is undergoing Phase 2 clinical evaluation for the treatment of hepatic encephalopathy, a life‐threatening condition marked by elevated neurotoxins in patients with advanced liver disease.
