Despite not meeting the primary end point, those in the early-start group showed reduced change from baseline in MDS-UPDRS-III scores compared with the delayed-start group at both weeks 52 and 104.
Treatment with prasinezumab (Roche), an investigational humanized monoclonal antibody previously known as PRX002, resulted in slight delay of motor progression, leading to more favorable trajectories in patients with Parkinson disease (PD). Investigators noted that this signal of change needs to be confirmed with additional studies.1
These results were from part 2 of the phase 2 PASADENA study (NCT03100149) and were presented at the International Parkinson and Movement Disorder Society (MDS) Virtual Congress 2021, September 17-22, by Gennaro Pagano, MD, MSc, PhD, expert medical director, Roche. Overall, 316 participants were recruited in the study, 309 of which started Part 2 and were included in the analysis. Patients included in the study had diagnosis of early PD, were drug-naïve or treated with monoamine oxidase B inhibitors.
Pagano and colleagues evaluated the efficacy of prasinezumab in an exploratory delayed-start analysis in individuals with early PD following 104 weeks of double-blind treatment. The humanized antibody is designed to bind to aggregated α-synuclein with higher selectivity over monomeric α-synuclein. By clearing a-synuclein clumps, the agent is thought to slow neurodegeneration associated with the protein’s toxic accumulation and its transmission to neighboring neurons.
Patients were randomized 1:1:1 to receive intravenous prasinezumab every 4 weeks (low dose [1500 mg] or high dose [3500 mg for body weight <65 kg or 4500 mg for body weight ≥65 kg) for 2 years (early-start group, n = 204) or placebo for 1 year, followed by prasinezumab (low or high dose) for 1 year (delayed-start group, n = 105).
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Signals of efficacy on motor progression were measured by changes in MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III score. At weeks 52 and 104, the early-start group showed an adjusted mean difference of –1.22 (standard error [SE], 1.08 [80% CI, –2.60 to 0.16]) and –1.93 (SE, 1.66 [80% CI, –4.07 to 0.20]), respectively, compared to those in the delayed-start group. Notably, digital motor score results were consistent with MDS-UPDRS Part III scores throughout the study (slope treatment interaction, 0.13 [SE, 0.067]; P = .049).
In April 2020, Roche announced that the trial had missed the primary efficacy outcome on the MDS-UPDRS, but generated positive signals on multiple secondary and exploratory end points.2 The company began a phase 2b study in patients with PD who have more advanced symptoms than that of PASADENA, called PADOVA (NCT04777331), in May 2021.3
PADOVA is enrolling 575 people who are on stable dopamine replacement medication and will use time to meaningful progression on the MDS-UPDRS Part III as the primary outcome. Patients in that study will receive prasinezumab or placebo for 18 months. Additional secondary outcome measures will assess motor function, clinical change, adverse events, pharmacokinectics, and antidrug antibodies.
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