130P Real-life outcome data on Risdiplam therapy for spinal muscular atrophy

Abstract

Risdiplam is an orally administered novel small molecule approved for the treatment of spinal muscular atrophy (SMA), a rare and debilitating neuromuscular disorder. Risdiplam acts as a survival motor neuron (SMN) 2 splicing modifier, promoting the production of functional SMN protein, which is crucial for motor neuron survival and function. By increasing SMN protein levels, risdiplam compensates for the deficiency caused by SMN1 gene mutations, the underlying genetic cause of SMA. We collected the clinical outcome data of all individuals with SMA treated with risdiplam at the SMA clinic in a large tertiary hospital. The study participants included 22 individuals who received risdiplam between 5 months and 24 years of age (median age 15 years, interquartile range [IQR] 12-21) and whose median follow-up duration was 16 ([IQR] 9.3-19.1) months. Of these patients, 18 were previously treated with intrathecal nusinersen and 4 patients were treatment naive. Compared to baseline, in SMA type 1 patients, Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) scores were stable or slightly increased by a median of 0.4 points at last follow-up, while in SMA types 2-3 patients Hammersmith Functional Motor Scale Expanded (HFMSE) scores showed a mild increase by a median of 2 points at last follow-up and Revised Upper Limb Module (RULM) scores showed an increase of 1 point. No changes in ventilatory status or bulbar function were noted during risdiplam follow-up. Five out of 22 patients had mild adverse effects, including headache, vomiting, nausea and rash which resolved within days. Overall, risdiplam was well tolerated, easy to handle and led to stable or slightly improved motor function outcomes in SMA patients.