Abstract
INTRODUCTION: Risdiplam, an oral splicing modifier for the survival motor neuron-2 gene (SMN2), is approved for treating spinal muscular atrophy (SMA). While its safety and efficacy have been demonstrated in global trials, there are limited real-world data on its safety in Japanese patients with SMA. This all-case postmarketing surveillance (PMS) study aimed to assess the safety and usage patterns of risdiplam in Japan. METHODS: This 12-month interim analysis is part of an ongoing PMS study that includes Japanese patients with SMA who have received risdiplam. The full observation period for this PMS is 24 months from the initiation of risdiplam treatment. Safety data, including adverse drug reactions (ADRs), were collected from case report forms (CRFs) submitted by participating healthcare facilities. ADRs were coded using the MedDRA/J classification. RESULTS: This study included 538 patients with SMA from 259 institutions in Japan between August 2021 and August 2022. The median age (minimum-maximum) at enrolment was 22.5 (0-83) years, and 51.5% of patients were male. SMA type II (47.2%) and III (27.9%) were the most common phenotypes. The median treatment duration was 366.0 days, and 86.1% of patients continued risdiplam treatment. ADRs were reported in 112 patients (20.8%), while serious ADRs were reported in eight patients (1.5%). The most common ADRs (classified by MedDRA System Organ Class) were gastrointestinal disorders in 86 (16.0%) patients (diarrhoea in 43 [8.0%], faeces soft in 23 [4.3%] and stomatitis in 10 [1.9%] patients). Exploratory analysis suggested that advanced age, comorbidities and concomitant medication use might be associated with an increased incidence of gastrointestinal ADRs. CONCLUSIONS: This 12-month interim analysis of PMS data indicated that risdiplam was well tolerated among Japanese patients with SMA, consistent with previous clinical trial findings. A comprehensive evaluation of the safety and efficacy of risdiplam will be provided in the final 24-month analysis.