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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 810-818 |
| Number of pages | 9 |
| Journal | Annals of clinical and translational neurology |
| Volume | 9 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2022 |
Funding
The authors would like to thank all the patients and families who participated in the risdiplam expanded access program, the program sites, and staff members. A full list of members of the EAP Working Group, who served as clinical investigators in the risdiplam EAP, is available in the Supplement Appendix . This program was funded by Genentech, Inc. The authors also thank Michelle B. Kim, PhD, of MediTech Media for providing medical writing support, which was funded by Genentech, Inc in accordance with Good Publication Practice (GPP3) guidelines ( http://www.ismpp.org/gpp3 ). JMK was a site principal investigator for the risdiplam EAP; she is currently the site principal investigator for Novartis clinical trials for which her institution receives research funding for clinical trial coordination. She has served on an SMA medical advisory board for Scholar Rock, Inc. NK serves on medical advisory boards for Astellas, Biogen, Novartis, Roche, Sarepta, and PTC Therapeutics. KJS has received research grant support from Biogen. AV has received compensation for ad‐hoc advisory boards/consulting activity with Biogen, Novartis, AveXis, Sarepta Therapeutics, PTC Therapeutics, Scholar Rock, and Fibrogen; and research/grant support from Muscular Dystrophy Association, Parent Project Muscular Dystrophy, Sarepta, Pfizer, Fibrogen, Genentech, Octapharma, Impax Laboratories, Lilly Pharmaceuticals, and Teva Pharmaceuticals. VKR has received personal fees from AveXis, Biogen, Genentech‐Roche, Scholar Rock, PTC Therapeutics, NSPharma, Regenxbio, Sarepta Therapeutics, France Foundation, Cure SMA, and MDA outside of the submitted work. BA, SBW, TLD, JH, HL, and YY are employees and shareholders of Genentech/F. Hoffmann‐La Roche. KA, HCP, and CS have no COIs to disclose.
ASJC Scopus subject areas
- General Neuroscience
- Clinical Neurology
