Pooled safety data from the risdiplam clinical trial development program

Topic:

Clinical Trials

Poster Number: 69

Author(s):

Laurent Servais MD, PhD, Giovanni Baranello , Enrico Bertini , Claudia Chiriboga MD, MPH, Basil T Darras MD, John W Day , Nicolas Deconinck , Dirk Fischer , Nathalie Goemans MD, PhD, Janbernd Kirschner , Andrea Klein , Riccardo Masson , Maria Mazurkiewicz-Bełdzińska , Yi Wang , Silvia Bader-Weder , Ksenija Gorni MD, PhD, Birgit Jaber , Tammy McIver , Renata S Scalco , Eugenio Mercuri MD, PhD

Institutions:

1. MDUK Oxford Neuromuscular Centre, 2. The Dubowitz Neuromuscular Centre, NIHR Great Ormond Street Hospital Biomedical Research Centre, 3. Department of Neurosciences and Neurorehabilitation, Bambino Gesù Children’s Research Hospital IRCCS, 4. Columbia University Medical Center, 5. Department of Neurology, Boston Children’s Hospital, Harvard Medical School, 6. Department of Neurology, Stanford University, 7. Neuromuscular Reference Center, UZ Gent, 8. Division of Neuropediatrics, University Children's Hospital Basel, University of Basel, 9. Neuromuscular Reference Center for Children, University Hospitals Leuven, 10. Clinic for Neuropediatrics and Muscle Disease, University Medical Center Freiburg, Freiburg, Germany, 11. University Children’s Hospital Basel, 12. The Dubowitz Neuromuscular Centre, NIHR Great Ormond Street Hospital Biomedical Research Centre, 13. Department of Developmental Neurology, Medical University of Gdańsk, 14. Children’s Hospital of Fudan University, 15. Pharma Development, Safety, F. Hoffmann-La Roche Ltd, 16. PDMA Neuroscience and Rare Disease, F. Hoffmann-La Roche Ltd, 17. Pharma Development, Safety, F. Hoffmann-La Roche Ltd, 18. Roche Products Ltd, 19. Pharma Development Neurology, F. Hoffmann-La Roche Ltd, 20. Universita Cattolica del Sacro Cuore

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 is a centrally and peripherally distributed oral SMN2 pre mRNA splicing modifier that increases the levels of functional SMN protein. Risdiplam (EVRYSDI™) has been approved by the FDA for the treatment of patients with SMA, aged 2 months and older.

The risdiplam clinical development program consists of four studies in a broad population of individuals with SMA:
•FIREFISH (NCT02913482) is a two-part study assessing the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy in infants with Type 1 SMA (inclusion criteria 1–7 months at enrollment)
•SUNFISH (NCT02908685) is a two-part study assessing the safety, tolerability, PK, PD and efficacy in patients with Type 2 or 3 SMA (inclusion criteria 2–25 years at enrollment)
•JEWELFISH (NCT0302172) assesses the safety, tolerability, PK and PD in patients with SMA (inclusion criteria 6 months–60 years at enrollment) who previously received RG7800 (RO6885247), nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec-xioi (ZOLGENSMA®).
•RAINBOWFISH (NCT03779334) assesses the efficacy, safety, PK and PD in infants (inclusion criteria birth-6 weeks at first dose) with genetically diagnosed and presymptomatic SMA.

Objective:
To determine the long-term safety profile of risdiplam in individuals with SMA who have participated in the risdiplam clinical development program.

Results:
Pooled analyses from FIREFISH Parts 1 and 2, SUNFISH Part 1 and JEWELFISH showed no treatment-related safety findings leading to withdrawal from risdiplam treatment for up to 39 months in 465 patients (data-cut: 15th January 2020). Here we will present updated pooled safety analyses for the risdiplam studies.

Conclusion:
This analysis will add to the understanding of the long-term safety profile of risdiplam.