PADOVA Trial Reports Prasinezumab Results in Early Parkinson Disease

Key Takeaways

• The primary endpoint was not met, although motor progression showed a directional difference favoring prasinezumab over placebo.
• Serious adverse events were similar between groups, and recorded deaths were considered unrelated to study drug.
• The authors said prespecified exploratory findings suggested clinical activity and supported continued evaluation in phase 3 PARAISO.

In the PADOVA phase 2b trial, median time to confirmed motor progression was 61.1 weeks with intravenous prasinezumab and 49.7 weeks with placebo in early Parkinson disease. That directional signal emerged in participants already receiving stable symptomatic medication. PADOVA tested the antibody in early-stage disease within a broader treated population than earlier treatment-naive or MAO-B inhibitor studies. The prespecified primary endpoint, however, was time to confirmed motor progression rather than the median estimate alone, and that endpoint was not met.

PADOVA was a multicentre, randomised, double-blind, parallel-group, placebo-controlled superiority trial conducted at 110 centres in nine countries across Europe and North America. Eligible participants were aged 50 to 85 years, were 3 months to 3 years from diagnosis, had Hoehn and Yahr stage 1 or 2 disease, and were receiving stable symptomatic medication. Between May 5, 2021, and March 22, 2023, investigators screened 787 people, randomly assigned 586, and reported 550 completed double-blind treatment. Participants, investigators, and clinical assessors were masked, and 1:1 assignment was to prasinezumab 1500 mg IV or placebo every 4 weeks for at least 76 weeks until target events. The prespecified primary endpoint was time to a confirmed motor progression event, defined by a 5-point increase in off-medication MDS-UPDRS Part III score.

In the primary analysis of the full analysis set, prasinezumab did not achieve statistical significance versus placebo for delaying confirmed motor progression. The hazard ratio was 0.84, with a 95% CI of 0.69 to 1.01 and a p value of 0.066. The estimates were directionally consistent with later progression in the active-treatment group, but the interval included no clear difference. The result therefore reflected a non-significant delay in motor progression rather than a positive primary efficacy finding.

Serious adverse events occurred in 34 of 292 participants, or 12%, with prasinezumab and in 34 of 290 participants, or 12%, with placebo. Three deaths occurred overall, including one in the prasinezumab group and two in the placebo group, and all were considered unrelated to study drug. The authors said prespecified exploratory findings suggested clinical activity and supported continued investigation in the ongoing phase 3 PARAISO trial.