After mid-stage Parkinson's failure, UCB remains upbeat for next two shots on goal

Elizabeth S. Eaton

SOURCE: https://firstwordpharma.com/story/5922159

Published : December 17, 2024

Ref: UCB

UCB said Monday that its Novartis-partnered Parkinson's disease hopeful missed the primary and key secondary endpoints of the Phase IIa ORCHESTRA study, notching another black mark against alpha-synuclein aggregate-targeting treatments.

The 18-month ORCHESTRA trial enrolled more than 450 patients with early-stage Parkinson's disease to receive either 180-mg or 360-mg daily doses of UCB's minzasolmin (UCB0599) or placebo. The company reported that the experimental treatment failed to slow progression on the Movement Disorder Society-Unified PD Rating Scale significantly more than placebo.

The oral alpha-synuclein misfolding inhibitor was the focus of a co-development deal inked with Novartis in 2021 potentially worth more than $1.5 billion. The Swiss pharma paid $150 million upfront to jointly advance the candidate with UCB, and also gained an option for the anti–alpha-synuclein monoclonal antibody (mAb) UCB7853 (see – ViewPoints: Novartis throws its hat in the alpha-synuclein ring).

Still pursuing alpha-synuclein

While UCB will be terminating an extension portion of the ORCHESTRA study, the company on Monday affirmed its commitment to UCB7853, along with glovadalen (UCB0022), an oral, brain-penetrant dopamine D1 receptor positive allosteric modulator (PAM). The mAb has completed a Phase I safety study, and glovadalen is in Phase II testing for Parkinson's.

"By leveraging the latest biological evidence, UCB's strategy includes investigating mechanisms to inhibit the misfolding and propagation of alpha-synuclein — processes believed to underlie the spread of neurodegeneration," said UCB's Chief Scientific Officer Alistair Henry. "Alongside this, we are advancing research into innovative therapies for symptom control, recognising the diverse needs of each patient throughout their disease trajectory."

However, experts have grown increasingly sceptical that targeting alpha-synuclein can produce disease-modifying effects in patients with Parkinson's. Gene and cell therapies, though further behind in development, may have a better chance of benefitting patients. For more on the Parkinson's disease treatment landscape, see Spotlight On: The slow march towards disease modification in Parkinson’s disease.