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.

Safety and Effectiveness of Natalizumab: First Report of Interim Results of Post-Marketing Surveillance in Japan.

INTRODUCTION: Natalizumab, a humanized anti-α4 integrin monoclonal antibody, received marketing approval in Japan in 2014 for the treatment of multiple sclerosis (MS). Because the previous large-scale clinical trials of natalizumab were mainly conducted in Europe and North American countries, and data in patients with MS from Japan were limited, we conducted an all-case post-marketing surveillance of natalizumab-treated MS patients from Japan to investigate the safety and effectiveness of natalizumab in a real-world clinical setting in Japan. Here, we report the results of an interim analysis. METHODS: During the observation period of 2 years, all patients who were treated with natalizumab subsequent to its approval in Japan were followed. The effectiveness of natalizumab was assessed by examining the changes in expanded disability status scale (EDSS) score and annualized relapse rate (ARR) from baseline. Safety was assessed by analyzing the incidence of adverse drug reactions (ADRs). RESULTS: The safety analysis included 106 patients (mean age 39.3 years; women 62.3%) whose data were collected until the data lock point (February 7, 2016). The effectiveness analysis included 75 patients. The majority of patients had relapsing-remitting MS (93/106 patients; 87.7%). The mean length of treatment exposure in the present study was 6.6 months. During the 2-year observation period, no significant change in the EDSS was observed, while the ARR decreased significantly from baseline (72.9% reduction, p = 0.001). ADRs and serious ADRs were observed in 11.3% and 3.8% of patients, respectively; however, no new safety concerns were detected. No patient had progressive multifocal leukoencephalopathy (PML) during the present study period. CONCLUSION: The safety and effectiveness of natalizumab were confirmed in Japanese patients with MS in clinical practice. Nevertheless, potential risks including PML require continuous, careful observation. FUNDING: Biogen Japan Ltd (Tokyo, Japan).

Safety and effectiveness of interferon ß-1a intramuscular therapy: results of the postmarketing drug surveillance in Japan.

To investigate the safety and effectiveness of the interferon ß-1a intramuscular injection under clinical conditions in Japan, we conducted an all-case postmarketing surveillance with a 2-year follow-up of patients who were registered during the period between November 2006 (product launch) and December 2010. Case reports were collected from 397 institutions. The safety analysis included 1,476 patients, and the effectiveness analysis included 1,441 patients. Of the patients included in the safety analysis, 86.3% had relapsing-remitting multiple sclerosis. The most common adverse drug reaction was pyrexia (19.24%). Serious adverse events included multiple sclerosis relapse (26 cases) and abnormal hepatic function (10 cases). In the effectiveness analysis, the annualized relapse rate improved significantly from 1.07 to 0.29 (P < 0.001). There was also a significant improvement in in the expanded disability status scale from 3.08 to 2.94 (P < 0.001). The results of the safety and effectiveness profile were consistent with those in previous reports.