P.065 AVXS-101 gene-replacement therapy (GRT)) in presymptomatic spinal muscular atrophy (SMA): study update

Abstract

patients and after treatment initiation for nusinersen-treated patients. Results: A total of 349 SMA1 patients (median age=1 year; 55.6% female) with median follow-up of 7.9 months were included. The proportion of patients receiving mechanical ventilation, nutritional support, and physical therapy/rehabilitation was 46.4%, 46.1%, and 22.6%. Patients had, on average, 59.4 days with medical visits/year (14.1 inpatient, 13.4 respiratory failure-related). The 45 nusinersentreated patients had, on average, 56.6 days with medical visits/year (4.6 inpatient, 11.4 respiratory failure-related). Excluding nusinersenrelated costs, mean healthcare costs PPPY were $137,627 (median: $43,167) for all patients and $92,618 ($29,425) for nusinersen-treated patients. Mean nusinersen-related costs were $191,909 ($144,487) per month for the first 3 months post-initiation and $36,882 ($16,132) per month thereafter. Conclusions: HRU and costs associated with SMA1 are substantial, even among patients treated with nusinersen.Background: SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. Methods: SUNFISH (NCT02908685) is an ongoing multicenter, double-blind, placebo-controlled, operationally seamless study (randomized 2:1, risdiplam:placebo) in patients aged 2-25 years, with Type 2/3 SMA. Part 1 (n=51) assesses safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Pivotal Part 2 (n=180) assesses safety and efficacy of the risdiplam dose level selected based on Part 1 results. Results: Part 1 results showed a sustained, >2-fold increase in median SMN protein versus baseline following 1 year of treatment. Adverse events were mostly mild, resolved despite ongoing treatment and reflected underlying disease. No drug-related safety findings have led to withdrawal (data-cut 06/17/18). SUNFISH Part 1 exploratory endpoint results and Part 2 study design will also be presented. Conclusions: To date, no drug-related safety findings have led to withdrawal. Risdiplam led to sustained increases in SMN protein levels.