Prasinezumab Misses Primary Endpoint in Roche’s Phase IIb Study, but Has Potential in Treating Early Stage Parkinson’s Disease

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Editor's note: this story was originally published on BioPharmInternational.com.

Roche announced results on Dec. 19, 2024 from a Phase IIb study (PADOVA) where prasinezumab, an investigational monoclonal antibody (mAb), failed to achieve statistical significance, missing the study’s primary endpoint. The study involved 586 patients with early stage Parkinson’s disease (PD) who were treated for a minimum of 18 months while on stable symptomatic treatment. Prasinezumab demonstrated potential clinical efficacy in the primary endpoint, which was time to confirmed motor progression, with a hazard ratio (HR)=0.84 [0.69-1.01] and p=0.0657, missing statistical significance, according to a company press release (1). The effect of prasinezumab, as evaluated in a pre-specified analysis, was more pronounced in the patients (75% of the participants) who were treated with levodopa, with results showing a HR=0.79 [0.63-0.99]. It was also observed that consistent positive trends occurred across multiple secondary endpoints as well as exploratory endpoints.

Prasinezumab also remains well tolerated and no new safety signals were observed in the study. Roche is evaluating the data further and will work together with health authorities to determine what steps to take next.

“Parkinson’s is complex and devastating with no disease modifying treatment options available for the millions of people impacted,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, Roche, in the press release (1). “We believe the consistent efficacy trends from the Phase IIb study of prasinezumab merit further exploration. We will continue our close collaboration with the Parkinson’s community as we further evaluate the data to determine next steps.”

Both a Phase II study (PASADENA) and this Phase IIb study (PADOVA) will continue to give Roche a chance to explore the observed effects in both studies. Full results from the Phase IIb (PADOVA) study are expected to be presented at an upcoming medical meeting.

Prasinezumab is part of a licensing, development, and commercialization agreement that Roche entered into with Prothena, an Ireland-based late-stage clinical biotechnology company with expertise in protein dysregulation. Under the agreement, formed in December 2013 (1), the companies aim to develop and commercialize mAbs that target α-synuclein, a presynaptic neuronal protein that is genetically and neuropathologically linked to PD (2). Prasinezumab targets the build-up of α-syn protein in the brain, which can potentially prevent further accumulation and spreading between cells. This action can slow down the progression of the disease (1).

“The results from the Phase [IIb] PADOVA study are a significant step forward to potentially bring the first disease-modifying treatment option to the millions of individuals living with Parkinson’s disease and their families,” said Gene Kinney, PhD, president and chief executive officer, Prothena, in that company’s press release (3). “As pioneers in developing the first anti-alpha synuclein targeting antibody, we look forward to Roche presenting the results from the PADOVA study at an upcoming medical conference and sharing with health authorities to determine the most appropriate path forward.”

References

1. Roche. Roche’s Phase IIb Study of Prasinezumab Missed Primary Endpoint, but Suggests Possible Benefit in Early-Stage Parkinson’s Disease. Press Release. Dec. 19, 2024.
2. Stefanis, L. α-Synuclein in Parkinson's Disease. Cold Spring Harbor Perspect. Med. 2012, 2 (2), a009399. DOI: 10.1101/cshperspect.a009399.
3. Prothena. Roche’s Phase IIb Study of Prasinezumab Missed Primary Endpoint, but Suggests Possible Clinical Benefit in Early-Stage Parkinson’s Disease. Press Release. Dec. 19, 2024.