BioVie’s stock fell by nearly 50% as the biotech claimed victory in a mid-stage Parkinson’s disease trial using an alternative endpoint to the one submitted to the FDA.
BioVie declared that the SUNRISE-PD Phase 2 study was a success based on a combined analysis of observed improvements in motor and non-motor symptoms.
But results for the primary outcome, a measure of motor function, were not presented. Company execs consistently referred to the results as “exploratory” in prepared remarks, and BioVie noted that the findings will help build the design of a future Phase 3 trial.
“These exploratory results suggest that bezisterim may have the potential to become the first drug candidate to improve clinical outcomes in Parkinson’s disease beyond motor symptoms,” BioVie CEO Cuong Do said in a prepared statement about the trial, which was designed to primarily measure motor symptoms.
Investors sent BioVie’s stock spiraling on the murky update, with shares down nearly 50% to around $1 since the market opened on Thursday.
The study enrolled 57 patients with early-stage Parkinson’s disease who had not received previous carbidopa/levodopa (sold as Rytary) treatment. The double-blind, placebo-controlled trial centers around bezisterim, formerly called NE3107, an oral small molecule designed to cross the blood-brain barrier and serve as both an anti-inflammatory and insulin-sensitizing agent.
The study’s only primary endpoint, as per ClinicalTrials.gov, is the change from baseline over 12 weeks on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). The tool examines both motor and non-motor measures across four parts, with SUNRISE-PD using MDS-UPDRS III to examine motor function as its main endpoint. The first two parts—non-motor experiences of daily living and motor experiences of daily living—are listed as secondary endpoints.
“Patients treated with bezisterim demonstrated statistically significant improvements compared to placebo on both motor and non-motor symptoms, as assessed by MDS-UPDRS Parts I, II and III, as well as a composite endpoint comprising 15 clinically relevant measures,” BioVie said Thursday.
But BioVie didn’t share any specifics—like statistical significance or lack thereof—tied to the MDS-UPDRS III primary endpoint. Instead, the biotech combined 15 motor and non-motor measures—including MDS-UPDRS I, II, III and MDS-UPDRS total—together for a composite endpoint dubbed EPNIC-15.
“The majority of patients treated with bezisterim showed improvement on EPNIC-15,” the company said.
BioVie also touted several exploratory biomarker improvements and shared figures for several of the findings that were statistically significant. The main pharmacodynamic assessment included in BioVie’s statistical analysis plan submitted to the FDA focused on changes in a panel of blood-based inflammatory markers, according to the company.
“The trial successfully met prespecified endpoints and achieved its objectives, with topline results showing that bezisterim improved blood based inflammatory markers of disease, along with a broad range of biological markers associated with overall cellular health and nerve cell damage,” BioVie said.
The biotech notably didn’t specify which endpoints—primary or secondary—were met, but declared that patients who received the therapy had greater improvements in clinical outcome measures of daily living, motor symptoms and non-motor symptoms than those who got placebo. The company also suggested that patients with higher levels of inflammation at the start of the trial fared better. “Collectively, these results highlight bezisterim’s potential to represent a meaningful advance in Parkinson’s disease treatment and provide a strong foundation for its continued clinical development,” Do added.
As for safety, BioVie said bezisterim was well tolerated, with 51.7% of adverse events reported in patients who received placebo compared to 39.1% on the experimental drug. No severe or serious adverse events were recorded, but a treatment-related adverse event was reported in both placebo and bezisterim groups.
The biotech has set up a conference call next week to discuss the results.
Bezisterim is BioVie’s main asset, with clinical programs evaluating the candidate in Alzheimer’s disease and long COVID. This May, the company completed enrollment for a Phase 2 study testing bezisterim for the neurological symptoms of long COVID. The Phase 2 study is fully funded by the U.S. Department of War (formerly the Department of Defense).
In a previous mid-stage Alzheimer’s study, bezisterim failed to significantly move the needle for multiple measures of cognitive and functional performance when compared to placebo.
In late 2023, the company shared an analysis from a Phase 3 Alzheimer’s study that had enrolled 493 patients but had to disqualify data from almost half of the 39 sites due to “trial violations,” leaving only 57 patients evaluable.
