Safety and effectiveness of nusinersen, a treatment for spinal muscular atrophy, in 524 patients: results from an interim analysis of post-marketing surveillance in Japan.

PURPOSE: Nusinersen is an antisense oligonucleotide approved for the treatment of spinal muscular atrophy (SMA). A post-marketing surveillance (PMS) has been ongoing (August 2017-August 2025) in all patients in Japan who were administered nusinersen intrathecally in real-world clinical settings. We report the interim analysis results for safety and effectiveness. METHODS: This interim analysis was conducted using data collected from 524 patients whose case report forms were obtained at least once by May 30, 2022. Collected data included patient demographics and adverse events (AEs) for safety, and motor function assessments and Clinical Global Impressions of Improvement (CGI-I) for effectiveness. RESULTS: Of the 524 patients in the safety analysis set, 522 patients who were diagnosed with SMA were included in the effectiveness analysis (infantile-onset SMA [n = 153, 29.3%], later-onset SMA [n = 369, 70.7%]). The median duration of treatment was 785.0 (range 1-1549) days. AEs occurred in 35.9% of patients (49.0% in infantile-onset SMA and 30.6% in later-onset SMA). Nusinersen treatment significantly improved Hammersmith Infant Neurological Examination scores in patients with infantile-onset SMA and Hammersmith Functional Motor Scale-Expanded scores in patients with later-onset SMA for up to nearly 3 years. Based on CGI-I assessments, 98.5-100% of patients receiving nusinersen 'improved' or remain 'unchanged'. CONCLUSIONS: This interim analysis of the large-scale, all-case PMS in patients who were administered nusinersen in Japan supports the safety and effectiveness of nusinersen. The benefit-risk balance of nusinersen treatment remains favorable.

Real-world safety of nusinersen in Japan: results from an interim analysis of a post-marketing surveillance and safety database.

PURPOSE: Nusinersen is the first disease-modifying therapy to treat spinal muscular atrophy (SMA). This report describes the safety and effectiveness of nusinersen in Japanese clinical use using two data sources: an ongoing Japanese post-marketing surveillance (PMS) and the safety database of the marketing authorisation holder, Biogen . MATERIALS AND METHODS: The PMS is evaluating the safety and effectiveness of nusinersen in all patients treated with nusinersen in Japan between August 2017 and August 2025; this interim analysis included data up to May 30, 2019. Biogen safety database data up to June 30, 2019 were also included to capture adverse events (AEs) from after the interim analysis cutoff date. Collected data included medical history, dosage and administration, and AEs. Safety assessment included AEs and serious AEs (SAEs). Effectiveness analyses included motor function assessments and clinical global impressions of improvement. RESULTS: Of 271 patients in the PMS population, 94 had SMA type I (34.7%), and 177 had SMA types II-IV (65.3%). AEs occurred in 67 patients (24.7%) and SAEs in 23 patients (8.5%). The Biogen safety database contained reports of 345 AEs; the most common were pneumonia, headache, and pyrexia, consistent with symptoms of SMA and lumbar puncture. In the analysis set, 26.2% of patients receiving nusinersen showed motor function improvements and 99.6-100.0% showed overall improvement. CONCLUSION: In this interim analysis of the PMS and Biogen safety database, nusinersen had a favourable benefit-risk profile in Japanese patients with SMA.

Real-world safety and effectiveness of nusinersen, a treatment for spinal muscular atrophy, in 401 Japanese patients: results from an interim analysis of post-marketing surveillance.

Purpose: Nusinersen is an antisense oligonucleotide for the treatment of spinal muscular atrophy (SMA). A post-marketing surveillance (PMS) has been ongoing (August 2017-August 2025) in all patients in Japan who received intrathecal nusinersen in real-world clinical settings. We report the interim analysis results of safety and effectiveness.Methods: This interim analysis was conducted using data collected from 401 patients whose case report forms were obtained at least once by 30 May 2020. Collected data included patient demographics and adverse events (AEs) for safety, and motor function assessments and Clinical Global Impressions of Improvement (CGI-I) for effectiveness.Results: All 401 patients were diagnosed with SMA and were included in the safety and effectiveness analysis (infantile-onset SMA [n = 126, 31.4%], later-onset SMA [n = 275, 68.6%]). The median duration of treatment was 330 days (range 1-823 days). The incidence proportion of AEs was 31.7% (37.3% in infantile-onset SMA and 29.1% in later-onset SMA). The most common AEs were headache (4.5%), pyrexia (4.2%), and pneumonia (3.7%). The incidence proportion of serious AEs was 11.5%. Nusinersen improved motor function scores and was assessed as 'effective' based on CGI-I in 99.7-100% of patients.Conclusions: This interim analysis of the PMS in Japanese patients treated with nusinersen found no new safety concerns, with the type of AEs consistent with the expected safety profile. The benefit-risk balance of nusinersen treatment remains favorable.