Oral therapy shows encouraging results for early Parkinson’s disease
Small Phase 2 trial finds improvements in symptoms and daily functioning
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- The experimental oral therapy bezisterim is being studied for early-stage Parkinson’s disease and is designed to reduce brain inflammation and improve insulin sensitivity.
- In a subgroup with higher platelet counts, bezisterim significantly improved motor and nonmotor symptom scores compared with placebo.
- Biovie is planning a larger Phase 3 clinical trial to further evaluate bezisterim's safety and effectiveness in early-stage Parkinson's disease.
In a small proof-of-concept clinical trial, Biovie’s experimental oral therapy bezisterim was associated with significantly greater improvements in motor and nonmotor symptom scores than a placebo among people with early-stage Parkinson’s disease who had higher levels of a potential inflammation marker. The findings come from an exploratory subgroup analysis.
In the broader group of patients included in the efficacy analysis of the Phase 2 SUNRISE-PD trial (NCT06757010), those receiving bezisterim were also more likely than those given a placebo to show meaningful improvement on an exploratory measure combining Parkinson’s symptoms and daily functioning.
The findings were presented in a poster titled “Bezisterim (NE3107) in Early Parkinson’s Disease (SUNRISE-PD): Initial Results and Observations From a Phase 2 Hybrid Design Trial” at the 151st Annual Meeting of the American Neurological Association, held recently in San Diego, California.
Early findings support further Parkinson’s research
“These results provide evidence that an anti-inflammatory treatment can benefit both motor and, importantly, non-motor symptoms of Parkinson’s disease,” Clarence Ahlem, Biovie’s senior vice president and program lead for Parkinson’s disease, said in a company press release. “Because non-motor symptoms remain a significant unmet need, the breadth of activity observed with bezisterim is particularly encouraging for its development as a treatment for early Parkinson’s disease.”
The new data add to previously reported positive top-line results and support Biovie’s plans to test bezisterim in a larger Phase 3 trial. The company has requested a meeting with the U.S. Food and Drug Administration (FDA) to discuss the proposed study, which could enroll about 175 people with early-stage Parkinson’s.
Research suggests that inflammation in the brain, called neuroinflammation, may play a role in Parkinson’s by contributing to damage and the gradual loss of nerve cells that produce dopamine.
Dopamine is a chemical messenger that helps control movement. As dopamine levels fall, people with Parkinson’s may develop motor symptoms such as tremor, stiffness, and slowed movement. Parkinson’s also causes nonmotor symptoms, including sleep problems, trouble with thinking and memory, depression, and anxiety.
Studies have also found problems with how the brain responds to insulin, a hormone that helps cells use blood sugar for energy. This impaired signaling may affect how nerve cells use energy and contribute to nerve cell damage in Parkinson’s.
Oral therapy targets inflammation and insulin resistance
Bezisterim is an investigational oral therapy designed to enter the brain and reduce inflammation. It also aims to improve insulin sensitivity, which is how well cells respond to insulin. By targeting inflammation and insulin resistance, bezisterim may help address processes thought to contribute to Parkinson’s symptoms and disease progression.
SUNRISE-PD enrolled 57 people with early-stage Parkinson’s who had not previously been treated with levodopa, a commonly used medication for movement symptoms. Limited prior use of levodopa for diagnostic testing was allowed. Participants were randomly assigned to take either 20 mg of bezisterim or a placebo twice daily for 12 weeks, or about three months.
Researchers measured changes in markers of inflammation, motor and nonmotor symptoms, daily functioning, sleep, and overall clinical benefit.
The new analyses focused on a group identified before the data were analyzed: participants whose platelet counts were above 230 billion per liter of blood at the start of the trial. Platelets are small blood cell fragments that help blood clot. Higher platelet counts may be a sign of inflammation throughout the body, also called systemic inflammation.
Among the 27 patients in this subgroup, those receiving bezisterim had statistically significant improvements in motor and nonmotor symptom scores compared with those receiving a placebo.
Researchers used the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), a standard tool for assessing Parkinson’s symptoms and their effects on daily life. Its sections measure nonmotor symptoms, difficulties with daily activities, and motor symptoms. For the motor assessment, researchers used a modified version that omitted tests of muscle stiffness and postural stability. Bezisterim was associated with significantly greater improvements than placebo in nonmotor symptom scores, motor symptom scores, and the overall score.
The subgroup also showed significantly greater improvement with bezisterim than placebo on the Composite Benefit Score (CBS), an exploratory measure combining several aspects of Parkinson’s symptoms and daily functioning.
Higher platelet counts linked to stronger treatment response
“Enhanced response in non-motor, motor, and motor [activities of daily living] symptoms, with clinical motor engagement observed in those with [initial] platelet counts above the study median,” the researchers wrote in the poster. “This represents an inflammation signal that informs an enriched study population and a biomarker for future phase 3 trials.”
In the broader group of patients included in the efficacy analysis, 25% of those receiving bezisterim had clinically meaningful improvements on the CBS, compared with 4% receiving a placebo. This meant patients taking bezisterim were more than six times as likely to show meaningful improvement on this exploratory measure.
Meanwhile, 14% of patients receiving bezisterim showed clinically meaningful worsening on the CBS, compared with 46% receiving a placebo. This represented a 70% lower risk of worsening on the exploratory measure with bezisterim.
Bezisterim was generally well tolerated. No severe or serious adverse events were reported in either group.
“We believe these findings provide an important foundation for future studies and support the development of bezisterim as a treatment with the potential not only to provide symptomatic benefit, but also to impact the underlying disease process and potentially slow disease progression,” Ahlem said.
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