At the recently held AD/PD 2025 International Conference on Alzheimer’s and Parkinson’s Diseases (PD), Roche announced topline results of prasinezumab in patients with early Parkinson’s disease (PD) on stable symptomatic treatment (PADOVA [NCT04777331]). The presentation highlighted the potential of prasinezumab at delaying PD motor progression as assessed with time-to-event endpoints, says GlobalData.
Christie Wong, Managing Neurology Analyst at GlobalData, comments, “While prasinezumab failed to reach primary endpoint of time to confirmed motor progression, as defined by ≥5 in MDS-UPDRS Part III OFF medicated state, the alpha-synuclein inhibitor has shown promise of delaying the decline of function in patients with early-PD on stable symptomatic treatment, as measured by the time to ≥3 points in MDS-UPDRS Part II. Furthermore, when compared to the patients who received placebo, the patients treated with prasinezumab took longer to reach meaningful worsening in Clinician Global Impression of Change (CGI-C), Patient Global Impression of Change (PGI-C), and time to ≥1 in MDS-UPDRS Part IV.”
In addition, a trend towards the reduction of motor progression was indicated with prasinezumab at week 104 but prasinezumab showed no effect at week 76. The effect of prasinezumab on delaying motor progression was more pronounced in the patients who received levodopa therapy, which accounted for 75 per cent of the total participants.
Wong adds, “The PADOVA study was not statistically powered to measure the long-term efficacy of prasinezumab and Roche has proposed that a treatment duration of longer than 18 months may be needed to measure the treatment effect on PD progression. As such, it will be interesting to see the open label extension results where more than 90 per cent of the patients opted to enroll into.”
A key opinion leader interviewed by GlobalData expressed interest in assessing the time to confirmed motor progression, as defined by ≥5 in MDS-UPSRS Part III during patients’ ON state, when symptomatic treatment is working well, in addition to the OFF state evaluated by Roche. This could provide additional insight into the treatment effect of prasinezumab on PD progression when PD motor symptoms are being managed by symptomatic treatments.
Wong notes, “The utilisation of the time-to-event clinical endpoint highlights the challenges Roche and other pharma companies have when investigating pipeline assets for PD modification.”
The current medications used for the treatment of PD are limited to those providing symptomatic relief of motor symptoms. The KOLs previously interviewed by GlobalData have emphasised the need for a disease-modifying therapy that can slow the progression of PD. But the development of pipeline assets that aim to slow PD progression is halted by the lack of clinical endpoints and biomarkers to evaluate disease progression.
Wong concludes, “The time-to-event endpoints in the PADOVA study hint that prasinezumab may have clinical benefit at slowing disease progression in patients with early PD on stable symptomatic treatment but the translation to real-word settings including assessment during both medication ON and OFF state remain to be seen.”