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


Clinical Trials

Poster Number: 70


Claudia A. Chiriboga, MD, MPH, Columbia University Medical Center, Claudio Bruno, Translational and Experimental Myology Centre, Istituto Giannina Gaslini, Tina Duong, Department of Neurology, Stanford University, Dirk Fischer, Division of Neuropediatrics, University Children's Hospital Basel, Janbernd Kirschner, MD, Medical Center-University of Freiburg; University Hospital Bonn, Faculty of Medicine, Eugenio Mercuri, Paediatric Neurology and Centro Clinico Nemo, Catholic University and Policlinico Gemelli, Fondazion, Marianne Gerber, MD, Pharma Development, Safety, F. Hoffmann-La Roche Ltd, Ksenija Gorni, MD, PDMA Neuroscience and Rare Disease, F. Hoffmann-La Roche Ltd, Heidemarie Kletzl, Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Imogen Carruthers, Roche Products Ltd, Carmen Martin, Roche Products Ltd, Francis Warren, Roche Products, Ltd, Mariacristina Scoto, UCL & Great Ormond Street Hospital Trust

Spinal muscular atrophy (SMA) is a severe, 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 by the FDA for the treatment of patients with SMA aged 2 months and older.

JEWELFISH (NCT03032172) is a multicenter, open-label study of daily risdiplam in non-naïve patients with SMA (inclusion criteria aged 6 months to 60 years at enrollment) who had previously received RG7800 (RO6885247), nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec (ZOLGENSMA®).

JEWELFISH (N=174) assesses the safety, tolerability and pharmacokinetic/pharmacodynamic (PD) relationship of risdiplam in non-naïve patients.

The enrolled population included a broad range of ages (1–60 years), SMA types (1–3), SMN2 copy numbers (1–4) and motor functions (non-sitters, sitters and walkers). We previously presented safety data from 173 patients (data-cut: 31 July 2020) who received risdiplam for up to 41 months. One patient withdrew from the study at baseline; of the remaining patients, 13 had previously received RG7800, 76 had received nusinersen, 70 had received olesoxime and 14 had received onasemnogene abeparvovec. Risdiplam treatment led to a rapid and sustained >2-fold increase in SMN protein levels compared with baseline levels (data-cut: 1 June 2020), which was consistent with PD data from the SUNFISH study of treatment-naïve patients with Types 2/3 SMA. No drug-related safety findings leading to withdrawal were reported for any patient exposed to risdiplam in JEWELFISH. The safety profile of risdiplam was consistent with the safety profile observed in treatment-naïve patients.

Here we will present 12-month safety, PD and exploratory efficacy data from JEWELFISH (data-cut: 29 January 2021).

The JEWELFISH study is ongoing at sites across Europe and the US and will provide important data on the safety, PD and exploratory efficacy of risdiplam in a broad population of non-naïve patients with SMA.