OBJECTIVES: Therapies that slow disease progression are a major unmet need in neurodegenerative diseases, such as Parkinson’s disease (PD). Disease-modifying treatment effects are usually reported in terms of differences in outcome measures which can be difficult to interpret, especially by patients. Here we aim to explore an interpretable quantification of time delay of two PD therapies rasagiline (approved symptomatic PD therapy with potential disease-modifying effects) and prasinezumab (investigational anti-α-Synuclein antibody), based on published trial results.

METHODS: Rasagiline and prasinezumab explored their potential for disease modification in two delayed-start trials (ADAGIO 36+36 weeks and PASADENA 52+52 weeks). Neither trial met primary endpoints but showed some promise for disease modification. Based on reported trial results, we calculate approximate estimates of the mean time-delay observed in the main and delayed-start parts of both trials.

We focus on Unified Parkinson's Disease Rating Scale (UPDRS) total score (ADAGIO) and Movement Disorder Society UPDRS part III (PASADENA).

RESULTS: At 36 weeks, both doses of rasagiline demonstrated delays in progression of more than 18 weeks (>50% slowing) compared to placebo representing both the symptomatic and potentially disease-modifying effect. At 72 weeks (36 weeks after delayed start of placebo group), the slowing of progression compared to the delayed-start cohort was maintained for the low dose (appx. 24 weeks), suggesting a potential disease-modifying effect, while the high dose showed no slowing.

At 52 weeks, prasinezumab slowed progression by appx. 38% (20 weeks) compared to placebo. At 104 weeks (52 weeks after delayed start of placebo group) the delay in progression was maintained (appx. 28 weeks).

CONCLUSIONS: Results from ADAGIO and PASADENA are inconclusive, due to differences in results across doses or outcomes. Regardless, estimation of time delays by methods such as the progression model for repeated measures could be helpful in quantifying disease-modifying aspects of treatments.