Analysts at Jefferies give Roche and Prothena’s Phase III study just a 25% to 40% probability of success.
Roche and Prothena are forging ahead to late-stage studies for their investigational Parkinson’s disease antibody prasinezumab even though it missed the bar in a mid-stage trial late last year.
In a note to investors on Monday morning, analysts at Jefferies said that while this decision could be an incremental positive for Prothena, the payout will “take patience.” Given the prior failure, the analysts aren’t optimistic about the prospects of this new late-stage trial, giving it a 25% to 40% probability of success.
Prothena’s shares rose 7.3% as the markets opened Monday, trading at $5.40 versus $5.08 at market close on Friday.
“A primary debate here is whether the antibody approach is potent enough to ‘slow the spread’ of an intra-cellular protein,” Jefferies explained. In this case, the analysts questioned whether prasinezumab, a monoclonal antibody that works outside the cell, can efficiently engage and arrest its target alpha-synuclein, a small protein that causes progressive neuron death in Parkinson’s.
The news comes after the Ireland-based biotech announced last week that it was letting go of 91 employees from its California site. The layoffs, which will take effect Aug. 1, follow a Phase III AL amyloidosis stumble in May.
In its press announcement on Monday, Roche focused on what Chief Medical Officer Levi Garraway called “efficacy signals” for prasinezumab in the mid-stage trial. In particular, the pharma maintained that Phase IIb data point to a potential clinical benefit of the investigational antibody when used on top of symptomatic treatment in the disease’s early stages.
Roche also homed in on “positive trends” in motor progression at two years, as well as biomarker evidence to support the effect of prasinezumab on Parkinson’s disease biology.
“We would note Roche continues to refine and enrich the studies to try and find the best patient population,” the Jefferies analysts wrote on Monday, adding that “by changing things each time – this also modifies risk.” The failed Phase IIb study, for instance, was conducted on a patient group that had been modified from the Phase IIa trial, yet the pharma still “got mixed results,” as per Jefferies.
Roche and Prothena have yet to disclose details regarding the timeline and design of the Phase III program.
In December 2024, the partners announced that prasinezumab fell short of its primary efficacy endpoint in the Phase IIb PADOVA study, unable to significantly improve motor progression in patients with Parkinson’s disease. However, they argued that the magnitude of effect at the time—16% with a p-value of 0.0657—showed “potential clinical effect.”
Roche bought into the potential of Prothena’s prasinezumab in December 2013 in a $600 million deal, including a $45 million upfront payment.
