An expanded access program of risdiplam for patients with Type 1 or 2 spinal muscular atrophy

Abstract

Objective: The US risdiplam expanded access program (EAP; NCT04256265) was opened to provide individuals with Type 1 or 2 spinal muscular atrophy (SMA) who had no satisfactory treatment options access to risdiplam prior to commercial availability. The program was designed to collect safety data during risdiplam treatment. Methods: Patients were enrolled from 23 non-preselected sites across 17 states and treated with risdiplam orally once daily. Eligible patients had a 5q autosomal recessive Type 1 or 2 SMA diagnosis, were aged ≥2 months at enrollment, and were ineligible for available and approved SMA treatments or could not continue treatment due to a medical condition, lack/ loss of efficacy, or the COVID-19 pandemic. Results: Overall, 155 patients with Type 1 (n = 73; 47.1%) or 2 SMA (n = 82; 52.9%) were enrolled and 149 patients (96.1%) completed the EAP (defined as obtaining access to commercial risdiplam, if desired). The median treatment duration was 4.8 months (range, 0.3-9.2 months). The median patient age was 11 years (range, 0-50 years), and most patients (n = 121; 78%) were previously treated with a disease-modifying therapy. The most frequently reported adverse events were diarrhea (n = 10; 6.5%), pyrexia (n = 7; 4.5%), and upper respiratory tract infection (n = 5; 3.2%). The most frequently reported serious adverse event was pneumonia (n = 3; 1.9%). No deaths were reported. Interpretation: In the EAP, the safety profile of risdiplam was similar to what was reported in pivotal risdiplam clinical trials. These safety data provide further support for the use of risdiplam in the treatment of adult and pediatric patients with SMA.

Risdiplam in Patients Previously Treated with Other Therapies for Spinal Muscular Atrophy: An Interim Analysis from the JEWELFISH Study

“…The safety profile of risdiplam in patients treated for 12 months (CCOD 29 January 2021) reported in this interim analysis is consistent with results reported in treatment-naïve individuals in the FIREFISH [ 23 , 24 ] and SUNFISH studies [ 26 ]. There were no safety signals observed across the whole JEWELFISH study population, including patients previously treated with nusinersen or onasemnogene abeparvovec.…”

“…To date, there is one report that describes the evaluation of onasemnogene abeparvovec followed by risdiplam, which was well tolerated in patients with type 1 SMA [ 22 ]. Another report from the risdiplam expanded access program showed patients treated with risdiplam who were either treatment-naïve or had been previously treated with nusinersen, onasemnogene abeparvovec, or both had a similar safety profile to those in pivotal risdiplam clinical trials [ 23 ]. Currently, there is one ongoing study (RESPOND; NCT04488133) evaluating the safety and efficacy of nusinersen in 60 patients following treatment with onasemnogene abeparvovec [ 24 ].…”

Short-term safety results from compassionate use of risdiplam in patients with spinal muscular atrophy in Germany

“…An expanded access program (EAP) in the US with 73 patients with SMA1 and 82 patients with SMA2 also reported a similar safety profile for risdiplam as seen in pivotal clinical trials and no new safety signals [ 27 ].…”

Risdiplam for the treatment of adults with spinal muscular atrophy: Experience of the Northern Ireland neuromuscular service

“…There have been two recent studies on the safety of risdiplam in both children and adults outside of clinical trials with the most commonly reported treatment related adverse events being diarrhea, constipation, nausea, rash, and headache. 17,18 The studies did not report on the efficacy of treatment.…”

“…Minor rashes have commonly been reported with 14% and 17% of patients developing rashes in the FIREFISH study and SUNFISH part 2 study respectively 9,16 There were few other reported side effects in our cohort; none of these were serious. There have been two recent studies on the safety of risdiplam in both children and adults outside of clinical trials with the most commonly reported treatment related adverse events being diarrhea, constipation, nausea, rash, and headache 17,18 . The studies did not report on the efficacy of treatment.…”