JEWELFISH: 24-month safety, pharmacodynamic and exploratory efficacy data in non-treatment-naïve patients with SMA receiving treatment with risdiplam


Clinical Trials

Poster Number: 151


Claudia A. Chiriboga, MD MPH FAAN, Department of Neurology, Columbia University Medical Center, New York, NY, USA, Claudio Bruno, MD, Center of Translational and Experimental Myology, IRCCS Istituto Giannina Gaslini, Genoa, Italy, Tina Duong, PhD, Stanford University, Dirk Fischer, MD, Division of Neuropediatrics, University Children's Hospital Basel, Basel, Switzerland, Janbernd Kirschner, PhD, University Medical Center Freiburg, Mariacristina Scoto, MD PhD, Great Ormond Street Institute of Child Health UCL, & GOSH Hospital Trust, London, UK, Eugenio Mercuri, MD, PhD, Department of Paediatric Neurology and Nemo Clinical Centre, Catholic University, Marianne Gerber, MD, Pharma Development, Safety, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Ksenija Gorni, MD PhD, Roche, Heidemarie Kletzl, PhD, Pharmaceutical Research, Roche Innovation Center Basel, Basel, Switzerland, Imogen Carruthers, Roche Products Ltd, Welwyn Garden City, UK, Carmen Martin, PhD, Roche Products Ltd, Welwyn Garden City, UK, Teresa Gidaro, PhD, Development Neurology, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Francesco Muntoni, MD, UCL Institute of Child Health and Great Ormond Street Hospital for Children

Spinal muscular atrophy (SMA) is a progressive neuromuscular disease that affects individuals with a broad age range and spectrum of disease severity. Risdiplam (EVRYSDI®) is a centrally and peripherally distributed, oral survival of motor neuron 2 (SMN2) pre‑mRNA splicing modifier that has been approved in more than 90 countries worldwide.

JEWELFISH (NCT03032172) is a multicenter, open-label study of daily risdiplam in non-treatment-naïve patients with SMA (inclusion criteria: aged 6 months–60 years at enrollment) who were previously enrolled in the MOONFISH study (RG7800) or previously treated with nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec (ZOLGENSMA®).

To determine the safety, tolerability, pharmacokinetics and pharmacodynamics (PD) of risdiplam in non-treatment-naïve patients with SMA.

The enrolled population (N=174) included a broad range of ages (1–60 years), SMA types (1–3), SMN2 copy numbers (1–4) and motor functions (non-sitters/sitters/walkers). Of the 174 patients enrolled, 13 patients were previously enrolled in MOONFISH (three patients were treatment naïve as they had received placebo and never switched to RG7800), 76 received nusinersen, 70 received olesoxime and 14 received onasemnogene abeparvovec. One patient withdrew from the study at baseline. Risdiplam treatment led to a >2-fold increase in SMN protein versus baseline within 4 weeks, irrespective of previous treatment. No drug-related safety findings leading to withdrawal were reported for any patient. The safety profile of risdiplam was consistent with the safety profile in treatment-naïve patients treated with risdiplam in the FIREFISH (NCT02913482) and SUNFISH (NCT02908685) studies. Based on the exploratory efficacy analysis, an overall stabilization of motor function was observed following 24 months of risdiplam treatment in patients aged 2–60 years as assessed by the 32-item Motor Function Measure and Revised Upper Limb Module scales (data-cut: 31 January 2022).

JEWELFISH is ongoing at sites across Europe and the USA and is providing important data on the safety, PD and exploratory efficacy of risdiplam in a broad population of non-treatment-naïve patients with SMA.