5-year safety update: Risdiplam clinical trial program for spinal muscular atrophy (SMA)

Topic:

Clinical Trials

Poster Number: 230 M

Author(s):

Carol Jean Guittari, PhD, RPh, Genentech, Giovanni Baranello, MD, PhD, UCL Gt Ormond St Inst Child Health, London, UK, Laurent Servais, MD PhD, University of Oxford, Basil Darras, MD, Boston Children's Hospital, John Day, MD, PhD, Stanford, Nicolas Deconinck, Neuromuscular Reference Center, Michelle Farrar, MD, UNSW Sydney, Richard Finkel, MD, St Jude Children's Research Hospital, Enrico Bertini, MD, Bambino Gesù Children’s Research Hospital IRCCS, Rome, Italy, Janbernd Kirschner, MD, Medical Center-University of Freiburg, Freiburg, Germany, Riccardo Masson, MD, Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy, Maria Mazurkiewicz-Bełdzińska, MD, Department of Developmental Neurology, Medical University of Gdańsk, Gdańsk, Poland, Silvia Bader-Weder, MD, Pharma Development, Safety, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Ksenija Gorni, MD, PhD, PDMA Neuroscience, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Valerie Schlegel, MD, Pharma Development, Safety, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Yue Li, PhD, Pharma Development, Data Sciences, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Renata S Scalco, MD, PhD, Pharma Development Neurology, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Eugenio Mercuri, MD, PhD, Paediatric Neurology, Catholic University, Rome, Italy, Centro Clinico Nemo, IRCCS, Rome, Italy

Background
Risdiplam (EVRYSDI®) is a centrally and peripherally distributed, oral survival of motor neuron 2 (SMN2) pre‑mRNA splicing modifier approved for the treatment of SMA.

The risdiplam clinical development program consists of four clinical trials:
• RAINBOWFISH (NCT03779334) in infants with presymptomatic SMA (inclusion criteria [IC]: birth–6 weeks of age at first dose)
• FIREFISH (NCT02913482) in infants with Type 1 SMA (IC: aged 1–7 months at enrollment)
• SUNFISH (NCT02908685) in patients with Types 2/3 SMA (IC: aged 2–25 years at enrollment)
• JEWELFISH (NCT03032172) in patients with SMA (IC: aged 6 months–60 years at enrollment) who previously received RG7800 (RO6885247), nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec (ZOLGENSMA®)

Objectives
To determine the long-term safety profile of risdiplam in patients with SMA who have participated in risdiplam clinical trials.

Results
Previous analyses of 465 patients with symptomatic SMA from FIREFISH, SUNFISH and JEWELFISH (clinical cut-off dates [CCODs] November 22, 2022, September 6, 2022, and February 8, 2023, respectively) and 26 patients with presymptomatic SMA from RAINBOWFISH (CCOD February 20, 2023) showed that long-term treatment with risdiplam has a favorable safety profile. In patients with symptomatic SMA, the adverse event (AE) profiles of both the Type 1 and Types 2/3 SMA pools over the long-term remained consistent with a positive benefit–risk profile. In presymptomatic patients, the AE profile, aside from COVID-19 events, was consistent with their age.

Conclusion
The FIREFISH, SUNFISH, and JEWELFISH trials are complete. The full 5-year safety data will be reported in this safety update, adding to the understanding of the long-term safety profile of risdiplam. RAINBOWFISH safety data up to 3 years into the study will also be included.