Genentech's Phase IIb Study of Prasinezumab Suggests Early-Stage Parkinson's Benefit Despite Missing Primary Endpoint

Genentech, a part of the Roche Group, has shared promising findings from the Phase IIb PADOVA trial evaluating prasinezumab for early-stage Parkinson’s disease. The study encompassed 586 participants who were treated for at least 18 months while maintaining stable symptomatic treatments. Prasinezumab demonstrated potential efficacy regarding the primary goal of delaying motor progression, indicated by a hazard ratio of 0.84, though it narrowly missed statistical significance with a p-value of 0.0657. Interestingly, more pronounced effects were seen in participants concurrently taking levodopa, with a hazard ratio of 0.79. Consistent positive trends were also observed across numerous secondary and exploratory endpoints. The treatment was generally well tolerated, and no new safety concerns were reported.

Dr. Levi Garraway, Genentech's Chief Medical Officer, noted the complex and devastating nature of Parkinson’s disease, emphasizing the lack of treatments that modify disease progression. He expressed that the consistent efficacy trends observed in the Phase IIb study justify further investigation and highlighted the company’s commitment to working closely with the Parkinson’s community to decide on subsequent steps.

Both the Phase II PASADENA and the Phase IIb PADOVA studies will continue with open-label extensions to further investigate the observed effects. Genentech and Roche plan to scrutinize the data and engage with healthcare authorities to determine future directions. Detailed outcomes from the PADOVA trial are slated for presentation at an upcoming medical conference.

Prasinezumab, the investigational drug in question, is a monoclonal antibody designed to bind specifically to aggregated α-synuclein, aiming to reduce neuronal toxicity. By targeting α-synuclein accumulation in the brain, prasinezumab potentially prevents further build-up, thereby slowing disease progression. This approach is backed by substantial scientific evidence supporting the targeting of α-synuclein aggregates in Parkinson’s disease treatment.

Currently, prasinezumab is also being assessed in ongoing phases of the PASADENA and PADOVA studies. Four-year data from the PASADENA study, published in Nature Medicine, suggested a sustained slowing of motor progression when compared to a matched natural history cohort. The safety data for prasinezumab is derived from over 900 participants who have undergone treatment in various studies, with more than 500 participants receiving treatment for periods extending from 1.5 to 5 years.

Genentech and Roche have been in collaboration with Prothena since December 2013 to develop and commercialize monoclonal antibodies targeting α-synuclein, including prasinezumab, for Parkinson’s disease treatment.

The PADOVA study, a Phase IIb multicenter, randomized, double-blind trial, assessed prasinezumab against a placebo in 586 patients with early-stage Parkinson’s disease who were on stable symptomatic treatment. Participants received monthly intravenous doses of prasinezumab or placebo for a minimum of 76 weeks, followed by a two-year open-label extension phase where all participants are currently receiving active treatment.

The primary endpoint for PADOVA is the time to confirmed motor progression of Parkinson’s disease, defined as a 5-point increase in the MDS-UPDRS Part III score in an OFF medication state, which indicates significant motor progression.

Parkinson’s disease, a chronic and progressive neurodegenerative condition, affects over 10 million people worldwide, characterized by the gradual loss of dopamine-producing neurons and associated with both motor and non-motor symptoms. Although current treatments effectively alleviate motor symptoms, they do not halt disease progression, a gap that Genentech aims to address through ongoing research and development efforts.

Genentech is actively exploring various approaches to slow disease progression, including targeting α-synuclein aggregation, lysosomal dysfunction, and neuroinflammation.

As a pioneer in biotechnology, Genentech has been focusing on neuroscience, aiming to develop innovative therapies that improve the lives of people suffering from chronic and debilitating diseases. The company, headquartered in South San Francisco, continues to deepen its research in neurological disorders alongside its partners, pushing the boundaries of scientific understanding to tackle complex challenges in the field.