Prasinezumab (PRX002/RG7935), an antibody designed to eliminate the toxic clumps of alpha-synuclein in Parkinson’s disease patients, did not lessen the progression of motor and non-motor symptoms over one year, compared with a placebo, findings from a Phase 2 clinical trial show.
While the results mean that the PASADENA study (NCT03100149) did not achieve its primary goal, Roche — which is developing the therapy in collaboration with Prothena — said that prasinezumab has showed signs of efficacy on multiple secondary and exploratory measures.
The company will continue to evaluate the data to determine the next steps of prasinezumab’s development. An update is expected later this year, Prothena said in a press release.
Prasinezumab is designed to selectively eliminate the alpha-synuclein aggregates that contribute to Parkinson’s progression by inducing an immune response against these toxic protein clumps.
After being deemed safe and well-tolerated, and seen to efficiently lower alpha-synuclein in the blood of Parkinson’s patients, in a prior Phase 1b trial (NCT02157714), Roche launched the PASADENA study to determine whether prasinezumab also could prevent the progression of disease symptoms in patients.
The two-part trial included 316 patients diagnosed within the past two years, who were not on dopaminergic therapy and were not expected to need it for at least one year. Participants were recruited at 65 clinical sites across the U.S., France, Germany, Austria, and Spain.
In PASADENA’s first part, patients were assigned randomly to a high prasinezumab dose (4,500 or 3,500 mg, depending on body weight), a low treatment dose (1,500 mg), or a placebo, administered via intravenous (into-the-vein) infusions once every four weeks for one year.
Those who finished the one-year treatment then were eligible to enter the trial’s second part, in which all patients received prasinezumab for one more year. In this ongoing part, patients previously on prasinezumab are receiving the same dose as in part one, while those on prior placebo are assigned randomly to the high or low dose of prasinezumab.
The main goal of PASADENA is to determine if prasinezumab slows the progression of motor and non-motor symptoms over the first year – measured as changes in the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) total score (sum of Parts I, II, and III) from study start to end of part one.
Secondary goals include clinical and patient-reported measures of effectiveness. The level of neurodegeneration of dopamine-producing neurons, cognitive function, and need for dopaminergic therapy also will be evaluated.
Roche recently reported initial data from PASADENA’s participants, showing they represent a wide population of Parkinson’s disease patients, which makes them suitable to investigate therapies acting on disease progression.
Shortly after, in a sales update, the company reported that the trial did not meet its primary objective, meaning that prasinezumab was no better than a placebo at slowing the progression of Parkinson’s disease symptoms, but that signals of efficacy were nonetheless seen in other measures.
As in the Phase 1b trial, prasinezumab also was well-tolerated by patients in PASADENA and showed a favorable safety profile.
The extension part of PASADENA is ongoing, but Prothena announced that due to the COVID-19 pandemic some patients have been missing assessments. The full extent of disruptions caused by this outbreak, however, is yet to be determined.
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