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Phase 2 SUNRISE-PD Trial to Test Investigational Bezisterim as Disease-Modifying Therapy for Parkinson
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Bezisterim has shown potential in improving non-motor symptoms like fatigue and sleep issues, with promising results from previous studies.
Mark Stacy, MD
At the 3rd Annual Advanced Therapeutics in Movement and Related Disorders (ATMRD) Congress, held by the PMD Alliance from June 22-25, in Washington, DC, investigators presented an outline of the pivotal phase 2 SUNRISE-PD trial, a study assessing BioVie’s bezisterim, an oral, blood-brain barrier-permeable molecule in development for Parkinson disease (PD). The hope is that this hybrid study will provide important information on the benefits of this investigational agent, which would provide the foundation for a study of disease-modifying activity.1
Bezisterim, formerly known as NE3107, has anti-inflammatory and insulin-sensitizing activities via inhibition of inflammatory ERK and nuclear factor kappa B (NF-kB) activation and tumor necrosis factor-alpha (TNF-a) signaling. Pro-inflammatory cytokines, particularly TNF-a, may also have a role in sleep regulation and fatigue in patients with PD. Prior to SUNRISE-PD, it demonstrated promise in ameliorating specific non-motor symptoms of PD, particularly issues with fatigue and restlessness of the legs.
SUNRISE-PD is expected to included 60 patients who will be randomized to bezisterim 20 mg BID or matched placebo capsules 20 mg BID for a 16-week treatment period, with a 4-week follow-up. The trial, which comprises those with PD who are naïve to carbidopa/levodopa treatment, assesses the efficacy of bezisterim on motor symptoms of PD, explained through the modified Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III score. Of note, this primary end point will exclude rigidity and postural stability.
Presented by Mark Stacy, MD, a neurologist at the Medical University of South Carolina (MUSC), the study will include those age 45-80 years old with a diagnosis of idiopathic PD no more than 18 months prior to screening. Eligible patients must have mild unilateral or bilateral involvement without impaired balance, otherwise a Hoehn and Yahr stage of less than 3. If a patient enters while on medications for glycemic control, medicines must be stable for at least 3 months prior to the study and remain stable during the study. Notably, glucagon-like peptide-1 receptor agonists are not permitted.
Other secondary outcomes of the study include the impact of bezisterim on non-motor symptoms of PD and on overall symptoms of PD as assessed by the clinician. In addition, the study will also observed its effects on other aspects of PD using change in MDS-UPDRS combined and sub-domain scores. Patient-reported outcomes such as the Parkinson’s Disease Questionnaire and the Parkinson’s Disease Sleep Scale will also be utilized as exploratory end points.
Patients in the study may also participate completely from their home or a clinical site. If participating from home, a study nurse will visit the patient’s home and complete study assessments with the assistance of a neurologist who will join the home visit remotely by video. If the results of the study are positive, participants may be eligible to enter a longer-term open-label safety study at a future date.
The previously completed phase 2a study featured 46 patients with PD who had a history of motor fluctuations, bradykinesia, and motor response to levodopa who were randomly assigned 1:1 to either bezisterim 20 mg twice a day with immediate-release (IR) carbidopa/levodopa or placebo plus IR C/L for 27 days. In the bezisterim + C/L group, investigators observed changes of –18.6 and –15.6 on MDS-UPDRS-Part III at hours 2 and 3, respectively, in comparison to –16.2 and –12.8 with levodopa alone. These improvements were even greater among those aged less than 70 years old (bezisterim + levodopa: –20.2 and –17.0; levodopa: –16.3 and –12.3). For context, around 50% of the total patient population was less than 70 years old.2
Additional findings showed that more bezisterim-levodopa combination treated patients who experienced an OFF state at baseline experienced a morning ON state prior to dosing on day 28. All told, 6 of the 20 (30%) of those on the combination approach had ON state vs 0 of 19 placebo-treated patients (0%). This difference was considered statistically significant (P = .02). Within the bezisterim group, patients saw a –2.4 change (improvement) in Non-Motor Symptom Scale (NMSS) Sleep/Fatigue domain score, in comparison with those on placebo, who worsened by 1.0 points (P = .0159; cohen’s d = –0.5). Notably, sleep/fatigue domain improvements significantly correlated with motor score improvements (r = .51; P = .0259).
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