Source: GlobalData
There are currently no marketed disease-modifying therapies (DMTs) for Parkinson’s disease (PD). At the American Academy of Neurology (AAN) 2024 annual meeting, Roche presented positive four-year results from a six-year open-label extension of their Phase II “PASADENA” trial evaluating the efficacy of PRX-002 (prasinezumab), a potentially PD modifying monoclonal antibody. These latest results strengthen the hope that PRX-02 will be able to slow PD motor progression, according to GlobalData, a leading data and analytics company.
Lorraine Palmer, Pharma Analyst at GlobalData, comments: “While the first 52 weeks of the PASADENA trial were randomized, double-blind, and placebo controlled, subsequent years had all participants receiving prasinezumab in an open-label extension where long-term follow-up outcomes were presented. With no control arm present, Roche selected to use an open access dataset from the Parkinson’s Progression Marker Initiative [PPMI] observational study.”
To support the validity of the comparison to the external control, Roche applied the same inclusion and exclusion criteria to the PPMI cohort as was applied to the PASADENA cohort. Subsequently, propensity score weighting was applied to mimic the characteristics of a randomized controlled trial that compared the baseline characteristics and progression over one year of the PPMI cohort with the PASADENA placebo group from the first year.
When comparing the PPMI cohort back to the first year of the trial, there is no significant difference in PD progression between all cohorts, as measured by Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts I and II. This is in line with the PASADENA trial failing to meet its first-year primary endpoint as measured by sum of Parts I, II, III of the MDS-UPDRS. It is important to note that in this first year, there was no PD progression even in the PASADENA placebo, as measured by the MDS-UPDRS Parts I and II.
Palmer continues: “A potential treatment effect on disease progression can only be measured when participants in the placebo group progress sufficiently toward the endpoint of interest. Since this didn’t happen in the first year of PASADENA trial with the MDS-UPDRS Parts I and II secondary endpoints, these endpoints cannot be used to evaluate the effect of PRX-002 on PD progression for the first year. The reliability of the first-year readout for the primary endpoint is contentious. Additionally, positive outcomes from the first-year readout for the MDS-UPDRS Part III secondary endpoint suggested PRX-002 led to a slowing of PD progression. The inconsistencies in the year one results suggest that the open-label extension of the study to obtain longer-term outcomes was warranted.”
With the longer-term follow-up results from the open-label extension announced at AAN 2024, a significant shift can be seen in the treatment effect from three years of treatment onwards. At the three- and four- year intervals, the PRX-002 -treated cohort showed a significant reduction in PD motor progression as measured by MDS-UPDRS Part II and Part III scores, suggesting that PRX-002 slows PD motor progression in the longer-term.
Palmer adds: “Besides indicating positive outcomes with PRX-002, the results following the extension of the PASADENA trial highlight that in order to effectively measure the potential DMTs on the progression of patient-reported motor symptoms, functional activity of daily living, and the progression of non-motor symptoms, studies running for longer than one-year may be required.”
In addition, KOLs interviewed by GlobalData have stated high hopes for monoclonal antibodies targeting alpha-synuclein, such as PRX-02, for modifying-disease progression and offering neuro-protective effects.
Palmer concludes: “As an open-label exploratory extension, the results presented by Roche should still be treated as preliminary. However, considering that even prior to these latest results, PRX-002 was unanimously highly regarded by KOLs who were hopeful about its potential as a DMT offering neuroprotection, the recent results from the PASADENA extension greatly raises the anticipation for the conclusion of PADOVA, the ongoing Phase IIb trial evaluating PRX-002.”
