Real-world risdiplam effectiveness in adults with spinal muscular atrophy (SMA) from the Pediatric Neuromuscular Clinical Research (PNCR) registry

Topic:

Other

Poster Number: P391

Author(s):

Divya Jayaraman, MD, PhD, Department of Neurology and Pediatrics, Columbia University Irving Medical Center, New York, NY, USA, Spyros Roumpanis, MSc, F. Hoffmann-La Roche Ltd, Basel, Switzerland, William Martens, BA, Department of Biostatistics and Computational Biology, University of Rochester, New York, NY, USA, Travis Dickendesher, PhD, Genentech, Inc., South San Francisco, CA, USA, Sheila Shapouri, PharmD, MS, Genentech, Inc., South San Francisco, CA, USA, Basil T Darras, MD, Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA, Michio Hirano, MD, Houston Merritt Neuromuscular Research Center, CUIMC, New York, NY, USA, Zarazuela Zolkipli-Cunningham, MBBCh, The Children's Hospital of Philadelphia, Philadelphia, PA, USA, Anda Gershon, PhD, Genentech, Inc., South San Francisco, CA, USA

Background
Adults currently account for ~50% of the SMA population worldwide. Historically, untreated adults with Types 2 and 3 SMA demonstrate ongoing declines in motor function.
Risdiplam (EVRYSDI®) is a centrally and peripherally distributed oral survival of motor neuron 2 (SMN2) pre-mRNA splicing modifier that increases levels of functional SMN protein. Although clinical trial data, including data from SUNFISH (NCT02908685) and JEWELFISH (NCT03032172), show motor function stabilization in adults receiving risdiplam, real-world evidence is limited.

Objectives
To investigate real-world motor function outcomes of adults with SMA treated with risdiplam.

Results
Data were collected from adults with SMA enrolled in the Pediatric Neuromuscular Clinical Research Network registry from March 2017 to August 2024. Thirty-three patients aged ≥18 years were identified who had received risdiplam monotherapy; 20 of these had reported one pre- and ≥1 post-treatment motor function assessment, including the Hammersmith Functional Motor Scale – Expanded (HFMSE; n=5), Revised Upper Limb Module (RULM; n=12) and Revised Hammersmith Scale (RHS; n=5).
Of this patient population, the median age (range) was 29.0 (18–41) years. Most patients had Type 2/3 SMA (65% and 25%, respectively), and had three or ≥4 copies of the SMN2 gene (40% and 45%, respectively).
Five patients had pre- and post-treatment assessments using the HFMSE and RHS. Mean HFMSE and RHS scores remained stable over a follow-up of 6 (n=3) and 12 months (n=2). In 12 patients with pre- and post-treatment RULM assessments, mean RULM scores remained stable for up to 36 months of follow-up.

Conclusions
Results revealed stable motor function in adults receiving risdiplam monotherapy. When compared with the decline observed in the natural history of SMA, these data suggest an ongoing treatment benefit for up to 36 months. These findings should be interpreted with caution given the small sample size and limitations of the registry.