The maker of prasinezumab announced this week that the drug is moving into the critical, Phase III stage of clinical trials. If successful, the trial’s findings ultimately could be used to request approval from regulatory agencies, like the U.S. Food and Drug Administration (FDA), who would approve the drug for widespread use — potentially making prasinezumab among the first disease-modifying medications for Parkinson’s to become available to the public.
Prasinezumab targets a hallmark of Parkinson’s disease in the brain, which is the build-up of proteins that destroy dopamine neurons. The drug, being developed by the Swiss pharmaceutical company Roche, aims to stop this process. Scientists hope it could bind to those toxic alpha-synuclein proteins, limiting their damaging effects on the brain. Breaking this cycle could potentially stop the damage that causes Parkinson’s symptoms to get progressively worse over time — and even halt the disease entirely, so that symptoms could be minimized or potentially never emerge.
“Prasinezumab is at the leading edge of treatments aiming to target disease biology believed to underlie the brain cell degeneration seen in Parkinson’s disease,” said Brian Fiske, PhD, chief scientist at The Michael J. Fox Foundation (MJFF). “Success in the next clinical test of this approach would deliver a major advance in the ability to slow Parkinson’s disease progression, an option critically lacking today.”
Phase III is no small hurdle, in terms of both scale and time, and so if successful it would still be several years before the drug is available commercially. Phase III involves testing the drug in a large number of people — usually in the thousands. During this trial, researchers gauge a drug’s effectiveness, side effects and safety, and data from these trials are critical to securing FDA approval. The size of the Roche trial and its length have yet to be announced.
Roche’s Phase III trial will aim to answer the key question: Does prasinezumab achieve the goal of slowing or delaying the progression of the biology that leads to Parkinson’s symptoms, so that patients can experience slower worsening of symptoms and maintain their quality of life for longer than they would without the drug? In the best-case scenario, the drug would prove safe and effective and would be approved for widespread use in people with Parkinson’s. But even if the trial does not hit this ambitious goal, the trial process could offer important lessons into an important area of Parkinson’s research, said Sohini Chowdhury, MJFF’s chief program officer.
“This milestone trial will teach us a lot about targeting alpha-synuclein to treat Parkinson’s disease,” Chowdhury said. “We are heartened that Roche has made the decision to keep testing this first-in-class therapy and hopeful that the findings will move the field closer to the goal of a drug that can stop the disease in its tracks.”
Roche announced the decision to move forward with testing following two Phase II trials that demonstrated early signs of promise. The PADOVA trial tested the drug in people with early-stage Parkinson’s who also were receiving symptomatic treatment, such as levodopa. The PASADENA trial involved people with early-stage Parkinson’s who were not yet taking treatment for Parkinson’s symptoms.
The Michael J. Fox Foundation’s landmark longitudinal clinical study, the Parkinson’s Progression Marker’s Initiative (PPMI), played an instrumental role in supporting this testing. In one innovation, Roche used PPMI data from people with Parkinson’s at similar stages to those who were treated with prasinezumab in the Phase II PASADENA trial. In this way, PPMI participants served as a proxy control group. The comparison between people who received the drug (in PASADENA) and those who did not (in PPMI) showed that individuals treated with prasinezumab progressed more slowly. (While this is encouraging, it’s important to treat this data with cautious optimism, since it did not result from a gold-standard double-blind study.)
Drugs that target alpha-synuclein like prasinezumab are a major focus in Parkinson’s therapeutic development based on evidence that the misfolded protein plays a key role in the biology of Parkinson’s disease. Many therapies targeting alpha-synuclein are currently in clinical testing. Similar efforts in the Alzheimer’s field, targeting the beta-amyloid protein that is believed to play a fundamental role in that disease, ultimately led to the first approved drugs that reduce beta-amyloid clumps and help slow the progression of the disease.