by Isabella Colonna
For September we have selected two papers:
- Lang AE et al; SPARK Investigators. Trial of Cinpanemab in Early Parkinson’s Disease. N Engl J Med. 2022 Aug 4;387(5):408-420. doi: 10.1056/NEJMoa2203395.
- Pagano G et al; PASADENA Investigators; Prasinezumab Study Group. Trial of Prasinezumab in Early-Stage Parkinson’s Disease. N Engl J Med. 2022 Aug 4;387(5):421-432. doi: 10.1056/NEJMoa2202867.
Aggregated α-synuclein has been shown to play an important role in the pathogenesis of Parkinson’s disease. Here, we report the results of two phase 2 trials investigating α-synuclein-binding antibodies as potential disease-modifying treatment of Parkinson’s disease.
The first one, conducted by Lang et al., investigated Cinpanemab, a human-derived monoclonal antibody targeting extracellular α-synuclein versus placebo. This 52-week, multicentre, randomised, double-blind, placebo-controlled, phase 2 trial enrolled 357 patients with early-stage Parkinson’s disease. Participants were randomly assigned to receive placebo or cinpanemab at a dose of 250mg, 1250mg, or 3500mg, administered intravenously every four weeks. The trial was followed by an active-treatment, dose-blinded extension period (for a total period of up to 112 weeks). This study failed to show any benefit of treatment with cinpanemab as compared to placebo with regard to progression of motor and non-motor function, performing of activities of daily living, quality of life, or imaging biomarkers (DaT-SPECT).
The second trial, conducted by Pagano et al., investigated prasinezumab, a humanised monoclonal antibody binding aggregated α-synuclein at its C-terminal. This study reports the results of the first two parts (each one performed over 52 weeks) of the phase 2 trial of Anti α-Synuclein Antibody in Early Parkinson’s Disease (PASADENA), assessing the efficacy and safety of low-dose (1500mg) or high-dose (4500mg) prasinezumab, administered intravenously every four weeks, in 306 patients with early-stage Parkinson’s disease. The first part was double-blind and placebo controlled, while the second was a blinded extension in which all the individuals received active treatment. Part 3 is an ongoing, five-year open-label extension. The results of these two first parts of the trial did not show any benefit of treatment with prasinezumab over placebo on one-year disease progression assessed by the MDS-UPDRS score and on 123I-ioflupane SPECT imaging.
Although these two trials did not report any benefit of α-synuclein-binding antibodies in limiting the clinical progression of patients, further larger studies are needed in order to investigate a potential disease-modifying role of these molecules in patients with Parkinson’s disease.