JEWELFISH: Safety and pharmacodynamic data in non-naïve patients with spinal muscular atrophy (SMA) receiving treatment with risdiplam (RG7916)


Clinical Trials

Poster Number: 32


Claudia A. Chiriboga, MD, MPH, Claudio Bruno, John Day, MD, PhD, Tina Duong, Dirk Fischer, Janbernd Kirschner, Francesco Muntoni, MD, Sabine Fuerst-Recktenwald, Marianne Gerber, MD, Ksenija Gorni, MD, PhD, Heidemarie Kletzl, Francis Warren, Wai Yin Yeung, Eugenio Mercuri, MD


1. Columbia University Medical Center, New York, USA, 2. Translational and Experimental Myology Centre, Istituto Giannina Gaslini, Genoa, Italy, 3. Stanford, 4. Stanford University, Palo Alto, CA, USA, 5. University Children's Hospital Basel, University of Basel, Basel, Switzerland, 6. University Hospital Bonn, Faculty of Medicine, Bonn, Germany, 7. Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK, 8. Pharma Development Neurology, F. Hoffmann-La Roche Ltd, Basel, Switzerland, 9. Roche Innovation Center Basel, Basel, Switzerland, 10. PDMA Neuroscience and Rare Disease, F. Hoffmann-La Roche Ltd, Basel, Switzerland, 11. Roche Innovation Center Basel, Basel, Switzerland, 12. Roche Products Ltd, Welwyn Garden City, UK, 13. Roche Products Ltd, Welwyn Garden City, UK, 14. Department of Paediatric Neurology,Catholic University, Rome

on behalf of the JEWELFISH Study Group
Background: Spinal muscular atrophy (SMA) is a severe, progressive neuromuscular disease caused by reduced levels of survival of motor neuron (SMN) protein due to deletions and/or mutations of the SMN1 gene. A second SMN gene, SMN2, produces only low levels of functional SMN protein. Risdiplam (RG7916) is an orally administered, centrally and peripherally distributed SMN2 pre-mRNA splicing modifier that increases the levels of functional SMN protein.
JEWELFISH (NCT03032172) is an ongoing, multicenter, open-label study evaluating the safety, tolerability and pharmacokinetic/pharmacodynamic relationship of daily oral risdiplam in non-naïve patients with SMA.

To present data on safety and SMN protein levels in whole blood from patients in the JEWELFISH trial.

JEWELFISH participants, aged 6 months to 60 years, previously received RG7800 (RO6885247), nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec-xioi (ZOLGENSMA®).

Results and conclusions
We have previously presented safety data from 45 patients with SMA (data-cut, 28th June 2019) who received risdiplam for up to 28.9 months (nine patients previously received RG7800, 24 patients received nusinersen and 12 patients received olesoxime). No drug-related safety findings leading to withdrawal were reported. In an earlier analysis of SMN protein in whole blood, while patient numbers were limited (n=18), the magnitude of SMN protein increase (>2-fold) was comparable to that in SUNFISH Part 1 (NCT02908685) in patients with Type 2 and 3 SMA who had not previously received an SMN2-targeting therapy. The JEWELFISH study is currently recruiting in sites across Europe and the US.