Nusinersen effectiveness and safety in pediatric patients with Type II/III 5q-SMA: second interim analysis from a Chinese disease registry

Topic:

Clinical Trials

Poster Number: P2

Author(s):

Xiuxia Wang, The Second Hospital of Hebei Medical University, Xiaoli Yao, The First Affiliated Hospital, Sun Yat-sen University, Jing Peng, Xiangya Hospital Central South University, Rong Luo, West China Second University Hospital, Sichuan University, Hanbing Lu, Xuzhou Central Hospital, Jianmin Liang, The First Hospital of Jilin University, Xinguo Lu, Shenzhen Children's Hospital, Ruifeng Jin, Children's Hospital Affiliated to Shandong University, Liwen Wu, Hunan Children's Hospital, Jianmin Zhong, Jiangxi Provincial Children's Hospital, Lin Yang, The Second Affiliated Hospital of Xi’An Jiaotong University, Jihua Wu, Anhui Children's Hospital, Siqi Hong, MD, Children's Hospital of Chongqing Medical University, Yiyan Ruan, Maternity and Child Health Care of Guangxi Zhuang Autonomous Region, Tong Shen, Women and Children's Hospital, School of Medicine, Xiamen University, Xiaoli Zhang, The Third Affiliated Hospital of Zhengzhou University, Shanshan Mao, Children's Hospital Zhejiang University School of Medicine, Jun Hu, Fujian Medical University Union Hospital, Hua Wang, Shengjing Hospital of China Medical University, Dan Sun, Wuhan Children’s Hospital, Tongji Medical College Huazhong University of Science & Technology, Zhe Tao, Dalian Women and Children's Medical Group, Guanglu Yang, The Affiliated Hospital of Inner Mongolia Medical University, Guangbo Bian, People’s Hospital of Ningxia Hui Autonomous Region, Junlan Lv, MD, Beijing Children's Hospital, Capital Medical University, Li Zhang, Biogen Biotechnology (Shanghai) Co., Ltd, Junli Zhu, IQVIA Solutions Enterprise Management Consulting (Shanghai) Co., Ltd, Yi Wang, Children’s Hospital of Fudan University

Yi Wang is corresponding author.
Background and objective: To assess the effectiveness and safety of nusinersen for Type II/III 5q-spinal muscular atrophy (SMA) among Chinese children.

Methods: A multicenter, longitudinal registry was established to collect data retrospectively and prospectively from children with 5q-SMA across 25 sites in China. Treatment response was assessed at 6, 14 and 22 months post-nusinersen initiation based on motor measure changes. The correlation between changes in compound muscle action potential (CMAP) amplitudes and motor measures at 14 months was assessed using Spearman’s rank correlation coefficient. Safety was evaluated among participants initiating nusinersen post-enrollment.

Results: As of January 26th, 2024, a total of 513 participants with Type II (n=336) and III (n=177) 5q-SMA receiving nusinersen as the first disease-modifying therapy were included in the analysis. Consistent improvements were demonstrated in Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM) and 6-Minute Walk Test (6-MWT) over the 22-month period. The mean (SD) changes from baseline to 6, 14, and 22 months were 5.7 (6.52), 6.8 (6.65), 15.0 (8.63) in HFMSE, and 4.4 (3.50), 8.2 (3.68), 14.0 (1.73) in RULM, respectively, for sitters aged ≤ 5 years, and 3.1 (4.42), 4.1 (5.16), 4.9 (4.33) in HFMSE, and 2.7 (2.81), 3.4 (3.74), 5.2 (4.36) in RULM, respectively, for sitters aged > 5 years. Twenty-three participants with Type II 5q-SMA gained walking function post-nusinersen treatment. Regarding the changes from baseline to 14 months, a significant correlation was observed between HFMSE and RULM (ρ=0.42, p < 0.001), while no significant correlation was observed between motor measures and CMAP amplitude. Of the 131 participants with Type II/III 5q-SMA initiating nusinersen post-enrollment, two reported nusinersen-related adverse events (meningitis aseptic and myalgia), and no deaths occurred. Conclusion: Consistent with the first interim analysis, nusinersen demonstrated improvement in motor function and was generally well tolerated in Chinese children with Type II/III 5q-SMA. Disclaimer: This study was sponsored by Biogen. Writing and editorial support for the preparation of this abstract was provided by IQVIA: funding was provided by Biogen. Li ZHANG is an employee of Biogen and may hold stock in Biogen. Junli ZHU is an employee of IQVIA. Key words: Spinal muscular atrophy; Nusinersen; Pediatric; Registry