Objective: Evaluate efficacy and safety of prasinezumab following 52 weeks of treatment in participants with early Parkinson’s disease (PD).

Background: Prasinezumab is a humanized monoclonal antibody designed to target α-synuclein with the aim of slowing PD progression.

Method: PASADENA Part 1 (NCT03100149) was a 52-week multicenter, randomized, double-blind, placebo-controlled study evaluating intravenous prasinezumab (low [1500 mg] or high dose [4500 mg/3500 mg based on body weight]) versus placebo, in early PD (diagnosis ≤2 years at screening; Hoehn & Yahr Stages I–II, drug-naïve or treated with monoamine oxidase B inhibitors and not expected to require dopaminergic therapy for at least 52 weeks). The primary endpoint was change from baseline to Week 52 in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) total score (Parts I, II and III) versus placebo (using a mixed-effect model for repeated measures and including participants until the last visit before symptomatic treatment initiation). Secondary endpoints included change from baseline in MDS-UPDRS Part III and dopamine transporter imaging with single photon emission computed tomography (DaT-SPECT) in the putamen ipsilateral to the clinically most affected side.

Results: 316 participants were enrolled (Table: Baseline characteristics). The study did not meet the primary endpoint (–21.5% Low dose: –2.02 80% CI= –4.21–0.18; –6.6% High dose: –0.62 80% CI= –2.82–1.58). Signals of efficacy were observed in change from baseline in MDS-UPDRS Part III (–34% Low dose: –1.88 80% CI= –3.49 to –0.27; –18% High dose: –1.02 80% CI=–2.64–0.61) (Figure). Exploratory analyses, including MDS-UPDRS Part III central rating, digital endpoints and time to worsening of motor symptoms, supported this signal. DaT-SPECT signal changes showed no differences between groups, but there was limited progression (<11%) in placebo and treated participants. Prasinezumab was generally well tolerated with a favorable safety profile, no life-threatening adverse events or immunogenicity concerns.

Conclusion: PASADENA Part 1 did not reach the primary endpoint but prasinezumab showed a favorable safety profile and signal of efficacy on MDS-UPDRS Part III. PASADENA Part 2, a 52-week blinded extension assessing effects of prasinezumab on disease progression, is ongoing.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/pasadena-a-phase-2-study-to-evaluate-the-safety-and-efficacy-of-prasinezumab-in-early-parkinsons-disease-part-1-week-52-results/