At the AD/PD 2025 International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD), Roche announced topline results of prasinezumab in patients with early PD on stable symptomatic treatment (PADOVA). The presentation highlighted prasinezumab’s potential to delay PD motor progression as assessed with time-to-event endpoints and biomarker exploratory endpoints.
At the AD/PD 2025 ‘Advances in PD Treatment’ presentation, Roche announced that prasinezumab failed to reach its primary endpoint in the PADOVA study of time to confirmed motor progression, as defined by five or more points in Movement Disorder Society-Sponsored Revision of the Unified PD Rating Scale (MDS-UPDRS) Part III OFF medicated state. At week 76, prasinezumab showed no effect on motor progression, but a trend towards a reduction of motor progression was indicated with prasinezumab at week 104. Roche has proposed that a treatment duration of longer than 18 months may be needed to measure the treatment’s effect on PD progression. The PADOVA study was not statistically powered to measure the long-term efficacy of prasinezumab, but it will be interesting to see the results of the open-label extension, which more than 90% of the patients opted to enrol on. Prasinezumab’s effect on delaying motor progression was more pronounced in the patients who received levodopa therapy, which accounted for 75% of the total participants. Additionally, prasinezumab showed promise at delaying the decline of function in patients with early PD who were on stable symptomatic treatment, as assessed by the time to three or more points on MDS-UPDRS Part II in the presence of a confirmed motor event. 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, Patient Global Impression of Change, and time to one or more points in MDS-UPDRS Part IV. Roche stated that the time-to-event endpoint approach was defined as the meaningful threshold for a patient worsening, and was used to mitigate the impact of changing symptomatic treatments. A key opinion leader (KOL) interviewed by leading data and analytics company GlobalData expressed interest in assessing the time to confirmed motor progression, as defined by five or more points in MDS-UPSRS Part III during a patient’s ON state when symptomatic treatment is working well, in addition to the OFF state evaluated by Roche. This could provide additional insight into prasinezumab’s treatment effect on PD progression when PD motor symptoms are being managed by symptomatic treatments. The utilisation of the time-to-event clinical endpoint and KOL insight highlight the challenges that Roche and other pharma companies have when investigating disease-modifying properties of PD pipeline assets.
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During the presentation, Roche presented exploratory biomarkers that involved measuring changes in neuromelanin and the accumulation of iron using magnetic resonance imaging. At week 76, prasinezumab showed a trend towards a reduction of neuromelanin loss in the substantia nigra and less iron accumulation in the putamen and substantia nigra compared with placebo. These imaging findings indicate the potential for the development of a biomarker to measure the potential impact of prasinezumab on the underlying pathology of PD.
The current medications used for the treatment of PD are limited to those providing symptomatic relief of motor symptoms. KOLs previously interviewed by GlobalData have emphasised the need for a disease-modifying therapy that can slow the progression of PD. However, 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. The time-to-event endpoints and exploratory biomarkers in the PADOVA study indicate that prasinezumab may have clinical benefit at slowing disease progression in patients with early PD who are on stable symptomatic treatment, but the translation to real-world settings, including assessment during both medication ON and OFF state, remains to be seen.
