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

Abstract

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.

Keywords:

• Spinal muscular atrophy
• nusinersen
• post-marketing surveillance
• safety
• effectiveness

Acknowledgments

We thank all patients and healthcare professionals involved in the surveillance.

Authors’ contributions

All authors participated in the interpretation of surveillance results, and in the drafting, critical revision, and approval of the final version of the manuscript. Ryusuke Sato and Haruki Makioka were involved in the surveillance design and were responsible for the oversight of data collection and statistical analysis.

Prior presentation

The contents were presented at the 65th Annual Meeting of the Japanese Society of Child Neurology, May 25–27, 2023, Okayama, Japan and the 64th Annual Meeting of the Japanese Society of Neurology, May 31–June 3, 2023, Chiba, Japan.

Disclosure statement

All authors are employees of Biogen Japan.

Data availability statement

The data that support the findings of this surveillance are available from the corresponding author, Yosuke Tachibana, upon reasonable request.

Additional information

Funding

This work was supported by Biogen Japan (Tokyo, Japan). The sponsor was involved in the surveillance design, data collection, statistical analyses, and preparation of this manuscript. Medical writing assistance was provided by Yukiko Homma, MPharm, CMPP, and Rebecca Lew, PhD, CMPP, of ProScribe – Envision Pharma Group, and was funded by Biogen Japan. The manuscript, including ProScribe’s services, complied with international guidelines for Good Publication Practice.