Prasinezumab slows motor progression, misses main trial goal
Roche evaluating data as difference vs placebo not statistically significant
Treatment with investigational antibody therapy prasinezumab tended to slow the progression of motor symptoms in people with early-stage Parkinson’s disease in a Phase 2b trial, with particularly pronounced benefits among those also receiving levodopa.
However, the difference between prasinezumab and a placebo in the overall study population didn’t reach statistical significance — meaning it’s not certain that the outcome is not due to chance — so the trial failed its main goal.
Roche, which is developing prasinezumab in collaboration with Prothena Biosciences, reported that the treatment was safe and showed positive trends across other secondary and exploratory endpoints.
Because these findings from the Phase 2b PADOVA trial (NCT04777331) suggested a benefit of the investigational therapy, Roche believes prasinezumab still holds promise as a Parkinson’s treatment. The company said it plans to continue evaluating the trial data and will work with health authorities to determine the next steps for the therapy’s development. It will also present full PADOVA results at an upcoming conference.
“Parkinson’s is complex and devastating with no disease modifying treatment options available for the millions of people impacted,” Levi Garraway, MD, PhD, Roche’s chief medical officer and head of global product development, said in a company press release. “We believe the consistent efficacy trends from the Phase IIb study of prasinezumab merit further exploration. We will continue our close collaboration with the Parkinson’s community as we further evaluate the data to determine next steps.”
Slowing motor symptom progression
Parkinson’s disease is characterized by the toxic accumulation in nerve cells of the alpha-synuclein protein, which is believed to contribute to neurodegeneration. Prasinezumab is an antibody-based therapy designed to bind to these harmful clumps of alpha-synuclein and prevent them from further spreading throughout the brain, thereby slowing disease progression.
Results from the previous Phase 2 PASADENA trial (NCT03100149) showed that a year of prasinezumab failed to significantly slow the progression of Parkinson’s symptoms compared with a placebo, as assessed by the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS).
However, longer-term data from the study’s open-label extension (OLE) have since indicated that the treatment may be able to slow the progression of motor symptoms.
PADOVA enrolled 586 adults, ages 50-85, with early-stage Parkinson’s disease who were on stable regimens of symptomatic Parkinson’s treatments (levodopa or monoamine oxidase-B inhibitors).
They were randomly assigned to receive infusions into the bloodstream of prasinezumab (1,500 mg) or placebo once every four weeks on top of their symptomatic treatments for a minimum of 1.5 years.
The main goal was to evaluate the time to reach a confirmed and clinically meaningful progression of Parkinson’s motor symptoms. That was defined as at least a 5-point increase in the MDS-UPDRS Scale Part 3, assessed when patients were off of their symptomatic medications.
Roche reported that prasinezumab was associated with 16% lower odds of motor progression compared with a placebo, even though the results did not reach statistical significance and the trial failed its main goal.
In a pre-specified analysis involving the 75% of study participants who were being treated with levodopa, the effect of prasinezumab in delaying motor progression was more pronounced. There, the investigational therapy reduced the risk of motor progression by 21%.
Other measures of disease progression and safety were collected as secondary trial goals. Roche reported that consistent positive trends favoring prasinezumab were observed across multiple secondary and exploratory endpoints, but did not provide any details.
The treatment was well tolerated with no new safety signals observed.
After the main study, PADOVA participants could enter an ongoing OLE in which all are receiving prasinezumab for two years. Roche will use data from this study and the ongoing PASADENA OLE to further explore the possible benefits of prasinezumab.
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