Prasinezumab in Parkinson’s disease: delayed-start analysis of PASADENA trial

An efficacy signal of prasinezumab after 52 weeks in part 1 of the PASADENA study was further evaluated in an exploratory delayed-start analysis of part 2 of PASADENA. In patients with early Parkinson’s disease (PD), the difference in MDS-UPDRS Part III in the early-start versus the delayed-start group persisted after 104 weeks.

Prasinezumab is a humanised, monoclonal antibody specifically designed to target α-synucleinopathy (α-Syn) in PD. Prasinezumab demonstrated efficacy in multiple in vivo and cellular α-Syn-models. It has the potential to slow PD progression by protecting neurons from toxic α-Syn species.

The effect of prasinezumab was evaluated in the placebo-controlled, phase 2 PASADENA study (NCT03100149). The primary endpoint was the Movement Disorders Society–Unified Parkinson’s disease Rating Scale (MDS-UPDRS) sum of Parts I, II, and III at week 52. This endpoint was not met, but prasinezumab showed a favourable safety profile and a signal of reduction in clinical decline, as indicated by the MDS-UPDRS Part III bradykinesia score [1]. This persistent signal was further evaluated in early PD patients using a delayed-start analysis of part 2 (week 104) of the PASADENA study. Dr Gennaro Pagano (King’s College London, UK) presented the results [2].

Participants with early PD (diagnosis ≤2 years at screening) were randomised to intravenous prasinezumab every 4 weeks (1,500 or 4,500 mg) for 104 weeks (early-start group; n=204), or placebo for 52 weeks followed by prasinezumab (1,500 or 4,500 mg) for 52 weeks (delayed-start group; n=105).

Worsening from baseline in MDS-UPDRS Part III scores was less in the early-start group than in the delayed-start group (5.02 vs 6.25 points at week 52; 9.18 vs 11.12 points at week 104). The largest group difference was in the bradykinesia subscore. In the early-start group, fewer patients reached a ≥5-point increase in MDS-UPDRS Part III: 79.1% versus 89.5% in the delayed-start group (HR 0.77; 80% CI 0.66–0.91). Further studies will have to confirm these findings. The ongoing, phase 2b PADOVA (NCT04777331) study will further assess efficacy and safety of prasinezumab in early PD patients on stable symptomatic treatment.

1. Pagano G, et al. Mov Disord. 2020;35(suppl 1).
2. Pagano G, et al. A 104-week delayed-start analysis of PASADENA (Phase II study evaluating the safety and efficacy of prasinezumab in early Parkinson’s disease). S16.008, AAN 2022, 02–07 April, Seattle, USA.

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Posted on 2 June 202217 May 2024