Abstract Details

Title Number Needed to Treat (NNT) in Spinal Muscular Atrophy Type 1 (SMA1) with AVXS-101 Relative to Nusinersen

Topic Child Neurology and Developmental Neurology

Presentation(s) P1 - Poster Session 1 (5:30 PM-6:30 PM)

Poster/Presentation
Number 7-056

Objective To assess the NNT to prevent death and use of permanent assisted ventilation, and improve motor function, with onasemnogene abeparvovec (AVXS-101) compared with nusinersen in SMA1 patients.

Background SMA1 is a rapidly progressing neurologic disease that causes loss of motor and respiratory function. Until recently, SMA1 patients faced a poor prognosis with no approved treatments for their condition. Currently, nusinersen is the only FDA-approved SMA treatment; however, treatment with AVXS-101, a new gene-replacement therapy candidate, has recently demonstrated unprecedented survival and motor function in a phase 1 clinical trial.

Design/Methods Patients with SMA1 were treated with AVXS-101 (NCT02122952; cohort 2; N=12; up to 24 months) or nusinersen (NCT02193074; N=80; up to 13 months). NNT with AVXS-101 compared with nusinersen was assessed for survival and event-free survival (absence of death and permanent assisted ventilation) at last visit, and for motor function (≥4-point increase in CHOP-INTEND score from baseline) at last visit and at a median of 9 months. The NNT to prevent 1 death, 1 event (death or use of permanent assisted ventilation), or for 1 patient to improve motor function relative to nusinersen was calculated as the reciprocal of the difference between AVXS-101 and nusinersen in event rates or motor function achievement rates.

Results Mean age at first dose was 3.4 (0.9–7.9) and 5.3 (1.7–7.9) months in the AVXS-101 and nusinersen trials, respectively. NNT analyses suggested that treating 6.2 patients with AVXS-101 instead of nusinersen would prevent 1 more death; treating 2.6 patients with AVXS-101 versus nusinersen would prevent 1 more event; and treating 3.5 patients with AVXS-101 versus nusinersen would allow 1 more patient to improve motor function.

Conclusions Efficacy in preventing death and use of permanent assisted ventilation, and improving motor function, is much higher with AVXS-101 versus nusinersen.

Authors/Disclosures
Marcus Droege PRESENTER	No disclosure on file
Omar Dabbous	Omar Dabbous has received personal compensation for serving as an employee of Novartis Gene Therapies. Omar Dabbous has received stock or an ownership interest from Novartis Gene Therapies.
Martin Cloutier, MD	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file

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