On April 22, 2020, the pharmaceutical company Roche announced results from the first part of the PASADENA study, a Phase II clinical trial (human study) of its potential Parkinson’s treatment prasinezumab. This therapy, a monoclonal antibody, is one of many targeting the protein alpha-synuclein. Alpha-synuclein is the subject of intense interest by Parkinson’s researchers and the patient community, because it forms clumps in the brain that are suspected to be toxic and give rise to Parkinson’s disease. Thus, therapies that target these toxic forms of alpha-synuclein might protect brain cells and slow progression of Parkinson’s disease.
Though PASADENA did not meet its primary objective, it did show signs of providing benefit to study participants on multiple tests that were part of the study. Based on those positive signals, Roche is evaluating the data and exploring next steps for prasinezumab.
Prasinezumab is being developed through a collaboration between Roche and Prothena. To better understand these results and what the future holds for this potential therapy, we talked with Dr. Hanno Svoboda, Project Leader for prasinezumab at Roche, and Dr. Wagner Zago, Prothena’s Chief Scientific Officer, about the study.
The Michael J. Fox Foundation (MJFF): Can you give us a brief overview of the PASADENA study and the therapy it is testing?
Roche/Prothena (R/P): First, we’d like to thank the 316 individuals and their families who are participating in the PASADENA study and also the investigators. Their contribution enables us to advance the science that will hopefully lead to better therapies for people with Parkinson’s disease.
PASADENA is a Phase II study of prasinezumab, a therapy being studied for its potential to slow the progression of Parkinson’s disease. Phase II studies are typically designed to learn about a medicine’s safety and to estimate its potential benefit. Phase II studies test new medicines in fewer people with Parkinson’s before larger Phase III studies are initiated to ultimately confirm safety and efficacy that is required before a new therapy can be approved. Prasinezumab is an antibody that preferentially targets the toxic forms of alpha-synuclein believed to be associated with the onset and progression of Parkinson’s disease.
MJFF: The primary endpoint — or the predetermined measure of success in the trial — was a change over one year in the combined Parts I, II and III of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score, which measures both movement and non-movement symptoms. What did the study find?
R/P: The PASADENA study was designed for detection of potential signals of efficacy. While the study did not reach the prespecified level of statistical significance for the primary endpoint, it did show signals of efficacy on multiple prespecified secondary and exploratory clinical endpoints — predetermined measures that were also included to evaluate efficacy as part of the study. The study also demonstrated that prasinezumab was generally well-tolerated. At this time, we are continuing to evaluate the data to determine the possible next steps, including further clinical studies. We also plan to present the data at a medical conference.
MJFF: A year-long extension of the Pasadena Study is still underway. What data are participants providing now?
R/P: In Part two of the study, patients from the placebo arm of the study are now receiving prasinezumab. This part of the study is designed to give us further information about the long-term safety and efficacy of prasinezumab.
MJFF: Based on the results to date, what next steps are you considering for prasinezumab?
R/P: Prasinezumab is being developed to slow the progression of Parkinson’s disease. There are currently no treatments that target the underlying cause of the disease and can slow or stop disease progression. Developing new kinds of medicines requires the implementation of novel approaches and input from experts with a variety of scientific and medical perspectives. As part of our ongoing clinical development planning, we are talking with multiple stakeholders about what we have learned from PASADENA and how this data informs and supports our next steps.
MJFF: What would you tell patients and families who have been following this study with interest? Are you optimistic about the future of alpha-synuclein therapies for Parkinson’s disease?
R/P: Based on years of scientific research around alpha-synuclein and the combined evidence from animal studies, genetic clues and early clinical studies in humans, including the PASADENA study, we continue to be optimistic about the potential for therapies that target alpha-synuclein to provide a meaningful difference in the lives of people living with Parkinson’s disease and their caregivers. Both Roche and Prothena remain focused and dedicated to advancing treatments that have the potential to meet this goal and we look forward to sharing more information on prasinezumab as soon as possible.