OBJECTIVES

: Until recently, Type 1 SMA patients faced a poor prognosis with no approved treatments for their condition. Nusinersen is currently the only SMA treatment approved by the FDA; however, AVXS-101, a new gene replacement therapy candidate that has recently been evaluated in a Phase I clinical trial with promising results. The purpose of this analysis was to estimate the treatment effect of AVXS-101 relative to nusinersen for the treatment of Type 1 SMA.

METHODS

: In the absence of RCTs in both AVXS-101 and nusinersen with a common comparator, a Bayesian naïve indirect treatment comparison between AVXS-101 and nusinersen (ENDEAR trial) was conducted to compare relative efficacy and safety of AVXS-101 to nusinersen. The outcomes of interest were event-free survival (EFS), CHOP-INTEND response (≥4 point improvement), and overall and specific adverse events (AEs). Relative treatment effects were expressed as relative risk (RR), risk difference (RD) and number needed to treat/harm (NNT/NNH).

RESULTS

: At 12 months, 100% of patients on AVXS-101 were alive and not requiring ventilation, compared to 56% of patients on nusinersen, representing a 77% greater likelihood of EFS (RR of being alive and event-free 1.77, 95% CrI 1.49-2.20; RD 0.44, 95% CrI 0.19-0.39; NNT 2.30, 95% CrI 1.83-3.07). AVXS-101 also showed favorable results in terms of CHOP-INTEND response (RR 1.40; 95% CrI 1.23-1.65; RD 0.28, 95% CrI 0.18-0.40; NNT 3.52, 95% CrI 2.53-5.42). AVXS-101 and nusinersen showed similar safety profiles and rates of treatment emergent AEs (TEAE). Of the most frequently reported TEAE (vomiting, upper respiratory tract infection, cough, and constipation) none were considered AVXS-101 related, with most events related to patients’ underlying illness, not to study drug.

CONCLUSIONS

: Magnitude of the observed relative treatment effects indicates that AVXS-101 offers promising efficacy compared to nusinersen regarding EFS, reduced requirement for ventilation, and increased achievement of motor milestones.