Objective: To evaluate cinpanemab (BIIB054) efficacy and safety.

Background: Aggregated alpha-synuclein (α-syn), a major constituent of Lewy bodies, is thought to play a central role in the progression of PD. Cinpanemab (BIIB054) is a monoclonal antibody that preferentially binds to aggregated forms of α-syn, possibly slowing PD progression rate.

Method: Participants in SPARK, a randomized, double-blind, placebo-controlled study (NCT03318523) with an active-treatment dose-blinded extension period, were 40 to 80 years of age, diagnosed with PD for ≤ 3 years, had a score of ≤ 2.5 on the Modified Hoehn and Yahr Scale, and showed dopamine-transporter single-photon emission computed tomography (DaT-SPECT) results consistent with neurodegenerative Parkinsonism. In Year 1, randomization (2:1:2:2) was to placebo or cinpanemab 250 mg, 1250 mg, or 3500 mg. In Years 2-4, cinpanemab recipients continued on the same dose (early start), and placebo participants were re-randomized to one of three active treatments (delayed start). Primary endpoint was change from baseline in Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) total score (Parts I, II, and III) at Week (Wk) 52 and 72. Secondary endpoints included change from baseline to Wk 52 in striatal binding ratio (SBR) in the striatum, putamen, and caudate as measured by DaT-SPECT and incidence of adverse events (AEs) and serious adverse events (SAEs).

Results: There was no statistically significant difference in change from baseline in MDS-UPDRS total or Part score at Wk 52 between placebo and any cinpanemab group or at Wk 72 between early- and delayed-start groups. No significant differences or dose-response was observed between placebo and cinpanemab groups in change from baseline to Wk 52 in DaT-SPECT quantitative SBR values across the stratum or its subdivisions. In  Year 1, the percentage of participants reporting ≥1 AE was similar: cinpanemab (211/257, 82.1%) vs placebo (80/100, 80%).  Most participants in the cinpanemab group reported AEs of mild/moderate severity (195/211, 92.4%). The percentage reporting an SAE was also similar: cinpanemab (5.4%) vs placebo (7%); most SAEs were single events without a dose-related trend. Treatment discontinuation due to AEs was low in the cinpanemab group (1.6%).

Conclusion: In this study, there was no evidence of a cinpanemab treatment effect in PD as indicated by MDS-UPDRS scores and DaT-SPECT data. The safety profile was acceptable.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cinpanemab-in-early-parkinsons-disease-phase-2-spark-study-results/