P.376 - A series of case reports from JEWELFISH, an open-label study to investigate the safety, tolerability, and pharmacokinetics/ pharmacodynamics of RG7916 in adult and pediatric patients with spinal muscular atrophy who previously participated in a study with another SMN2-targeting therapy

Abstract

Spinal muscular atrophy (SMA) is a rare genetic disease caused by the mutation or deletion of the survival motor neuron 1 (SMN1) gene. SMA is characterized by progressive degeneration of spinal motor neurons, leading to muscle weakness and atrophy. Humans carry two, almost identical copies of SMN genes: SMN1 and SMN2. While SMN1 expresses full-length SMN protein, exon 7 is mostly skipped from SMN2 transcripts. RG7916 is a highly selective, orally available, investigational small molecule designed to modify the splicing of the SMN2 gene, resulting in the production of full-length SMN2 mRNA. JEWELFISH is a multicenter, open-label study evaluating daily oral administration of RG7916 (3 mg) in patients with SMA aged 12–55 years who have previously participated in a study with another SMN2-targeting therapy. A series of case reports from patients enrolled in this study will be presented. Data will include available safety and pharmacodynamics data. Together with the ongoing SUNFISH (SMA Type 2 and 3) and FIREFISH (SMA Type 1) studies, JEWELFISH will provide valuable insights into the safety, tolerability, and pharmacokinetics/pharmacodynamics of daily oral RG7916 treatment in SMA patients who have previously participated in a study with another SMN2-targeting therapy (i.e. RG7800 or nusinersen).