Roche's Parkinson's drug shows mid-stage promise, but misses mark

Pavan Kamat

SOURCE: https://firstwordpharma.com/story/5922642

Published : December 19, 2024

Ref: GlobeNewswire

Roche on Thursday unveiled a mixed bag of results from the Phase IIb PADOVA study of prasinezumab, an investigational treatment for early-stage Parkinson's disease, demonstrating a potential efficacy signal, whilst narrowly missing the primary endpoint. The readout was consistent with the drug's earlier mid-stage PASADENA study, which also reported mixed findings.

According to Roche, the monoclonal antibody — licensed from Prothena in 2013 — targets aggregated alpha-synuclein (α-syn) in the brain, preventing its accumulation and slowing down disease progression. This marks the second mid-stage failure for an anti-α-syn aggregate-targeting treatment in a week, after UCB's minzasolmin missed its goal in the ORCHESTRA study.

The PADOVA study enrolled 586 patients with early-stage Parkinson's disease on stable symptomatic treatment. Participants were assigned to monthly intravenous doses of prasinezumab or placebo for at least 76 weeks. The primary endpoint was time to motor progression on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale.

Hint of benefit..but misses significance

Results showed that prasinezumab demonstrated potential efficacy in delaying motor progression compared with placebo, yielding a hazard ratio (HR) of 0.84, though it marginally missed statistical significance. However, in a pre-specified analysis, the treatment effect was slightly stronger in levodopa-treated patients, with an HR of 0.79. Additionally, the company noted positive trends across several secondary and exploratory endpoints. In terms of safety, the therapy was well tolerated, with no new safety signals observed. The detailed data will be presented at a forthcoming medical conference.

Highlighting the dearth of disease modifying-treatments for Parkinson’s, Roche’s chief medical officer Levi Garraway, said "we believe the consistent efficacy trends from the Phase IIb study of prasinezumab merit further exploration." The company will continue the open-label extensions of both PASADENA and PADOVA, while discussing the findings with regulators to chart the drug's next steps.

Meanwhile, there is growing scepticism among experts that targeting α-syn can achieve disease-modifying effects in Parkinson's. Instead, gene and cell therapies — though early in development — are being viewed as more promising options. For more on the Parkinson's disease treatment landscape, read Spotlight On: The slow march towards disease modification in Parkinson’s disease.