Prasinezumab was originally developed by Prothena, an Irish biotech company, but licensed to Roche in December 2013. The big pharma has paid $135 million to Prothena so far for the drug candidate and for various development milestones including the start of the phase 1 and 2 trials.
The phase 2b PADOVA study assessed the efficacy of prasinezumab, a monoclonal antibody designed to bind to alpha synuclein in the brain and stop its aggregation and resulting neuronal toxicity, in 586 people with early-stage Parkinson’s disease.
The participants were on stable levodopa or monoamine oxidase-B inhibitor monotherapy for more than three months before enrollment. Study participants received prasinezumab or placebo every 4 weeks for at least 76 weeks during the study, before joining an ongoing open-label extension study where all participants received prasinezumab.
The trial did not meet its primary endpoint of change in time to confirmed motor progression. Prasinezumab did extend the time to motor progression by 16% versus placebo but this result just missed statistical significance (p=0.066).
Despite this, Roche stated that the drug candidate did meet several secondary and exploratory endpoints. It was also more effective in a sub-analysis of people taking levodopa who had a 21% increase in time to motor progression.
The side effect profile of prasinezumab remains good and it was well tolerated by participants of this study with no new safety concerns reported.
“Parkinson’s is complex and devastating with no disease modifying treatment options available for the millions of people impacted,” said Levi Garraway, Roche’s Chief Medical Officer and Head of Global Product Development, in a press statement.
“We believe the consistent efficacy trends from the phase 2b 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.”
A difficult disease to treat
Parkinson’s disease is a chronic neurodegenerative disease affecting more than 10 million people around the world where loss of dopamine producing neurons leads to both motor and non-motor symptoms.
Like other neurological and neurodegenerative diseases, Parkinson’s has proved challenging to treat. A study published in 2021 showed that less than 50% of potential Parkinson’s therapies developed since 1999 have managed to move from phase 2 to 3 and less than 15% have been approved.
Alpha-synuclein builds up in the brain of people with Parkinson’s and research has suggested it is a good target for therapeutics, but succeeding in this space has proved challenging. Earlier this week, it was announced that another potential candidate therapy targeting alpha synuclein called minzasolmin, developed by UCB and Novartis, also failed at phase 2. Earlier failures at targeting alpha synuclein include Biogen’s cinpanemab, which also failed at phase 2 in 2021.
Whether Roche will continue with prasinezumab development long term remains to be seen. The company says it is “further evaluating the data and will work together with health authorities to determine next steps.” It also stated that the phase 2 and phase 2b PASADENA open-label extension studies will continue.
