Type 1 SMA is a debilitating neuromuscular disease, in which untreated babies require nutritional assistance, permanent ventilation, and typically die before 2 years of age. SMA is caused by reduced levels of the survival of motor neuron (SMN) protein from deletions and/or mutations in the SMN1 gene. A second SMN gene, SMN2, produces only low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates SMN2 pre-mRNA splicing to increase SMN protein levels.

To determine the event-free survival rates (defined as alive and no need for permanent ventilation) and swallowing ability in babies with Type 1 spinal muscular atrophy (SMA) receiving risdiplam in the FIREFISH Part 1 dose-finding study.

FIREFISH (NCT02913482) is an ongoing, multicenter, open-label, operationally seamless study of risdiplam in infants aged 1–7 months at enrollment with Type 1 SMA and two SMN2 gene copies. Exploratory Part 1 (n=21) assesses the safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Confirmatory Part 2 (n=40) is assessing the safety and efficacy of risdiplam.

A Part 1 interim analysis (data cut-off September 7^th 2018), showed 19/21 babies (90.5%) were event-free at 10.5 months of age compared with 50% of babies at the same age (with two SMN2 gene copies) in natural history studies.¹ In Part 1, as of September 7^th 2018, no surviving infant has required tracheostomy, reached permanent ventilation or lost the ability to swallow. Updated data on event-free survival rates and swallowing ability will be presented based on 1-year data from the trial.

In the FIREFISH Part 1 dose-finding study, event-free survival rates were improved in babies with Type 1 SMA receiving risdiplam compared with babies of the same age in natural history studies.

Reference: 1. Finkel R, et al. Neurology 2014; 83:810–818.