Cinpanemab fails to slow disease progression in patients with early Parkinson's disease: NEJM
Toronto: In the phase 2 SPARK study trial, cinpanemab did not show any beneficial effect concerning clinical, imaging, or quality-of-life measures as compared to placebo in patients with early Parkinson's disease. The study article was published in the New England Journal of Medicine.
Globally, Parkinson's disease is the numerically fastest growing and the second most common neurodegenerative disorder. In Parkinson's disease, dopamine replacement has a substantial benefit concerning symptoms, but it does not slow disease progression. Also, there is a risk of developing levodopa-resistant symptoms over time, thus disease-modifying therapies beyond currently existing ones are needed. Aggregated α-synuclein plays an important role in Parkinson's disease pathogenesis. Cinpanemab, a human-derived monoclonal antibody targeting aggregated α-synuclein, is being evaluated as a disease-modifying treatment for Parkinson's disease.
Phase 1 study of Cinpanemab, suggested its dose-dependent biologic activity in persons with Parkinson's disease. Anthony E. Lang, the University of Toronto, Toronto, and his research team conducted a phase 2 trial to assess the clinical effect, safety, pharmacokinetics, and pharmacodynamics of intravenously administered cinpanemab in persons with early-stage Parkinson's disease. Researchers enrolled 357 participants with early Parkinson's disease for the 52-week trial. Participants were randomly assigned in a 2:1:2:2 ratio to receive intravenous infusions of placebo (control, n-100) or cinpanemab at a dose of 250 mg(n-55), 1250 mg(n-102), or 3500 mg(n-100) every 4 weeks, followed by an active-treatment dose-blinded extension period for up to 112 weeks.
The primary endpoints were the changes from baseline in the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score (range, 0 to 236, with higher scores indicating worse performance) at weeks 52 and 72. Secondary endpoints included MDS-UPDRS subscale scores and striatal binding as assessed on dopamine transporter single-photon-emission computed tomography (DaT-SPECT).
Key findings of the trial,
• The change in the MDS-UPDRS score at 52 weeks was 10.8 points in the control group, 10.5 points in the 250-mg group, 11.3 points in the 1250-mg group, and 10.9 points in the 3500-mg group (adjusted mean difference vs. control, −0.3 points P=0.90; 0.5 points, P=0.80; and 0.1 points, P=0.97, respectively).
• The adjusted mean difference at 72 weeks between participants who received cinpanemab through 72 weeks and the pooled group of those who started cinpanemab at 52 weeks was −0.9 points, 0.6 points, and −0.8 points for the dose of 250-mg, 1250-mg and 3500-mg dose, respectively.
• Results for secondary endpoints were similar to those for the primary endpoints.
• DaT-SPECT imaging at week 52 showed no differences between the control group and any cinpanemab group.
• The most common adverse events with cinpanemab were headaches, nasopharyngitis, and falls.
Researchers had to stop the trial after the week 72 interim analysis owing to lack of efficacy.
Researchers conclude that the effects of cinpanemab on clinical measures of disease progression and changes in DaT-SPECT imaging did not differ from those of placebo over 52 weeks in participants with early Parkinson's disease. Also, the adverse events in cinpanemab-treated participants were mostly mild to moderate in severity.
Reference:
Lang, Anthony E.,Siderowf Andrew D.,Macklin Eric A.,Werner Poewe et al. Trial of Cinpanemab in Early Parkinson's Disease New England Journal of Medicine 2022. doi: 10.1056/NEJMoa2203395
