AveXis, Inc., Bannockburn, IL, USA.
Precision Xtract, Oakland, CA, USA.
Adv Ther. 2019 May;36(5):1164-1176. doi: 10.1007/s12325-019-00923-8. Epub 2019 Mar 16.
Infants with spinal muscular atrophy (SMA) type 1 typically face a decline in motor function and a severely shortened life expectancy. Clinical trials for SMA type 1 therapies, onasemnogene abeparvovec (AVXS-101) and nusinersen, demonstrated meaningful improvements in efficacy (e.g., overall survival) but there were no head-to-head clinical trials assessing comparative efficacy. This study estimated the treatment effects of AVXS-101 relative to nusinersen for the treatment of SMA type 1.
Overall survival, event-free survival (no death or need to use permanent assisted ventilation), improvement in motor function [increase of ≥ 4 points in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score from baseline], and motor milestone achievements (head control, rolling over, and sitting unassisted) reported in the onasemnogene abeparvovec (AVXS-101-CL-101; NCT02122952) and nusinersen (ENDEAR; NCT02193074) clinical trials were indirectly compared using frequentist and Bayesian approaches.
Among symptomatic infants with SMA type 1, the number needed to treat (NNT) to prevent one more death with AVXS-101 instead of nusinersen was 6.2 [95% confidence intervals (CI) = 4.1-12.2], and the probability of preventing death was 20% higher for patients treated with AVXS-101 than nusinersen [risk ratio (RR) = 1.2, 95% CI 1.1-1.3]. For event-free survival, the NNT to prevent one more event was 2.6 (95% CI 2.0-3.6) and RR was 1.6 (95% CI 1.4-1.9). For improvement in motor function, NNT was 3.5 (95% CI 2.6-5.3) and RR was 1.4 (95% CI 1.2-1.6). For milestone achievements, the NNTs were 1.4 (95% CI 1.1-1.9), 1.5 (95% CI 1.1-2.5), and 1.2 (95% CI 1.0-1.5); RRs 4.2 (95% CI 2.6-6.7), 7.8 (95% CI 3.6-17.0), and 11.2 (95% CI 5.1-24.5) for head control, rolling over, and sitting unassisted, respectively. Results were similar using the Bayesian approach.
This indirect comparison (AVXS-101-CL-101 vs. ENDEAR) among symptomatic SMA type 1 infants suggests that AVXS-101 may have an efficacy advantage relative to nusinersen for overall survival, independence from permanent assisted ventilation, motor function, and motor milestones.
AveXis.
患有脊髓性肌萎缩症（SMA）1 型的婴儿通常会出现运动功能下降和预期寿命显著缩短。SMA 1 型疗法的临床试验，onasemnogene abeparvovec（AVXS-101）和 nusinersen，显示出在疗效方面的显著改善（例如，总生存率），但没有头对头的临床试验来评估比较疗效。本研究估计了 AVXS-101 相对于 nusinersen 治疗 SMA 1 型的治疗效果。
总体生存率、无事件生存率（无死亡或需要使用永久性辅助通气）、运动功能改善（费城儿童医院婴儿神经肌肉疾病测试（CHOP-INTEND）评分从基线增加≥4 分）和运动里程碑成就（头部控制、翻身和独坐）在 onasemnogene abeparvovec（AVXS-101-CL-101；NCT02122952）和 nusinersen（ENDEAR；NCT02193074）临床试验中进行了报告，并使用频率论和贝叶斯方法进行了间接比较。
在患有 SMA 1 型的有症状婴儿中，用 AVXS-101 替代 nusinersen 预防一人死亡的所需治疗人数（NNT）为 6.2[95%置信区间（CI）=4.1-12.2]，用 AVXS-101 治疗的患者死亡概率比用 nusinersen 治疗的患者高 20%[风险比（RR）=1.2，95%CI=1.1-1.3]。对于无事件生存率，预防一次事件的 NNT 为 2.6（95%CI=2.0-3.6），RR 为 1.6（95%CI=1.4-1.9）。对于运动功能的改善，NNT 为 3.5（95%CI=2.6-5.3），RR 为 1.4（95%CI=1.2-1.6）。对于里程碑成就，NNTs 分别为 1.4（95%CI=1.1-1.9）、1.5（95%CI=1.1-2.5）和 1.2（95%CI=1.0-1.5）；RR 分别为 4.2（95%CI=2.6-6.7）、7.8（95%CI=3.6-17.0）和 11.2（95%CI=5.1-24.5），分别为头部控制、翻身和独坐。使用贝叶斯方法得到的结果相似。
在患有 SMA 1 型的有症状婴儿中进行的这项间接比较（AVXS-101-CL-101 与 ENDEAR）表明，与 nusinersen 相比，AVXS-101 可能在总生存率、免于永久性辅助通气、运动功能和运动里程碑方面具有疗效优势。
AveXis。
