Roche's Parkinson's hope fails second clinical trial

An experimental therapy for Parkinson's disease being developed by Roche and Prothena has missed the mark in a phase 2b trial, leaving them sifting through the data for signals of efficacy.

The PADOVA trial of alpha-synuclein-targeting antibody prasinezumab wasn't able to show a statistically significant extension in the time to motor progression in patients with early-stage Parkinson's compared to placebo, missing its primary endpoint.

The disappointing result comes after prasinezumab flunked an earlier phase 2 trial called PASADENA that focused on global or imaging measures of Parkinson's progression, and also after another alpha-synuclein drug tested in the disease – Biogen's cinpanemab – was abandoned in 2021 after failed mid-stage trial.

There was another disappointment for the class earlier this year when Lundbeck's alpha-synuclein-targeting Lu AF82422 failed to reach statistical significance in patients with multiple system atrophy (MSA), another neurodegenerative disease with symptoms similar to Parkinson's.

Roche has accentuated the positive in the new, 586-subject study, pointing to a numerical delay in motor progression, as well as "positive trends" on as-yet-undisclosed secondary and exploratory endpoints. The company said it will present the data in full at a future medical congress.

"Parkinson's is complex and devastating, with no disease-modifying treatment options available for the millions of people impacted," commented Levi Garraway, Roche's chief medical officer and head of global product development.

"We believe the consistent efficacy trends from the phase 2b study of prasinezumab merit further exploration," he added. "We will continue our close collaboration with the Parkinson's community as we further evaluate the data to determine next steps."

Alpha-synuclein is a protein that tends to get misfolded and accumulates into clumps in the brains of patients with MSA and other diseases including Parkinson's, and is somewhat analogous to amyloid protein in Alzheimer's disease – which also led to a number of cul-de-sacs in clinical development before generating approved therapies.

Other clinical-stage drugs in the category include: Annovis Bio's buntanetap, an oral drug targeting alpha-synuclein, amyloid, and tau proteins that generated preliminary positive results in a phase 3 trial earlier this year; Takeda's antibody TAK-341 which disappointed in a phase 2 trial in Parkinson's, but remains in development for MSA; and Novartis and UCB's oral candidate minzasolmin, which is in phase 2.

Photo by Miikka Luotio on Unsplash