PMID- 38189761
OWN - NLM
STAT- MEDLINE
DCOM- 20240312
LR  - 20240330
IS  - 2214-3602 (Electronic)
IS  - 2214-3599 (Print)
IS  - 2214-3599 (Linking)
VI  - 11
IP  - 2
DP  - 2024
TI  - Risdiplam in Spinal Muscular Atrophy: Safety Profile and Use Through The Early 
      Access to Medicine Scheme for the Paediatric Cohort in Great Britain.
PG  - 361-368
LID - 10.3233/JND-230162 [doi]
AB  - BACKGROUND: Spinal muscular atrophy (SMA) is a progressive neuromuscular disease 
      caused by mutations in Survival motor neuron 1 (SMN1) gene, leading to reduction 
      in survival motor neuron protein (SMN), key for motor neuron survival and 
      function in the brainstem and spinal cord. Risdiplam is an orally administered 
      SMN2-splicing modifier which increases production of functional SMN protein. 
      Risdiplam was offered in the UK under early access to medicines scheme (EAMS) to 
      SMA type 1 and 2 patients aged 2 months and older, not suitable for authorised 
      treatments from September 2020 to December 2021. OBJECTIVE: To describe the 
      largest paediatric European real-world set of data on patients' characteristics 
      and short-term safety for risdiplam in Great Britain through EAMS. METHODS: We 
      collated data from SMA REACH UK a national clinical and research network for all 
      patients enrolled onto EAMS and assessed all submitted adverse events. RESULTS: 
      Of the 92 patients; 78% were Type 2 SMA, mean age 10.9 years, range 0-17 years. 
      56 were treatment naive, 33 previously treated; of these 25 had received 
      nusinersen, 3 previous treatment unknown. Sixty adverse events (AEs) were 
      reported occurring in 34 patients. The commonest were respiratory tract 
      infections and gastrointestinal disturbance. Four life-threatening events were 
      reported with 2 deaths and permanent cessation of risdiplam in 3 
      patients.Overall, 38/60 AEs were considered unrelated to risdiplam, 10/60 related 
      to risdiplam and for 12/60 causality not specified. CONCLUSIONS: This study found 
      a safety profile similar to clinical trials with no new safety concerns 
      identified. With the restricted eligibility of onasemnogene abeparvovec and 
      complications of nusinersen administration, EAMS allowed access or continued 
      treatment to naive patients or patients no longer suitable for approved 
      medications. Collection of longitudinal data for this complex population is 
      needed, to provide greater insights into risdiplam's role in addressing patients' 
      needs into the future.
FAU - Cornell, Nikki
AU  - Cornell N
AD  - The Dubowitz Neuromuscular Centre, Developmental Neuroscience Research and 
      Teaching Department, UCL Great Ormond Street Institute of Child Health, NIHR 
      Great Ormond Street Hospital Biomedical Research Centre & Great Ormond Street 
      Hospital NHS Foundation Trust, UCL Great Ormond Street Institute of Child Health, 
      London, UK.
FAU - Childs, Anne-Marie
AU  - Childs AM
AD  - Leeds Royal Infirmary, Leeds, UK.
FAU - Wraige, Elizabeth
AU  - Wraige E
AD  - Evelina London Childrens Hospital, London, UK.
FAU - Munot, Pinki
AU  - Munot P
AD  - The Dubowitz Neuromuscular Centre, Developmental Neuroscience Research and 
      Teaching Department, UCL Great Ormond Street Institute of Child Health, NIHR 
      Great Ormond Street Hospital Biomedical Research Centre & Great Ormond Street 
      Hospital NHS Foundation Trust, UCL Great Ormond Street Institute of Child Health, 
      London, UK.
FAU - Ambegaonkar, Gautam
AU  - Ambegaonkar G
AD  - Addenbrookes Hospital, Cambridge, UK.
FAU - Chow, Gabriel
AU  - Chow G
AD  - Queen's Medical Centre Nottingham, Nottingham, UK.
FAU - Hughes, Imelda
AU  - Hughes I
AD  - Royal Manchester Children's Hospital, Manchester, UK.
FAU - Illingworth, Marjorie
AU  - Illingworth M
AD  - University Hospital Southampton, Southampton, UK.
FAU - Majumdar, Anirban
AU  - Majumdar A
AD  - Bristol Royal Hospital for Children, Bristol, UK.
FAU - Marini-Bettolo, Chiara
AU  - Marini-Bettolo C
AD  - John Walton Muscular Research Centre, Newcastle University and Newcastle upon 
      Tyne Hospitals NHS Foundation trust.
FAU - Parasuraman, Deepak
AU  - Parasuraman D
AD  - University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
FAU - Spinty, Stefan
AU  - Spinty S
AD  - Alder Hey Children's Hospital, Liverpool, UK.
FAU - Willis, Tracey
AU  - Willis T
AD  - The Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, UK.
FAU - Scoto, Mariacristina
AU  - Scoto M
AD  - The Dubowitz Neuromuscular Centre, Developmental Neuroscience Research and 
      Teaching Department, UCL Great Ormond Street Institute of Child Health, NIHR 
      Great Ormond Street Hospital Biomedical Research Centre & Great Ormond Street 
      Hospital NHS Foundation Trust, UCL Great Ormond Street Institute of Child Health, 
      London, UK.
FAU - Baranello, Giovanni
AU  - Baranello G
AD  - The Dubowitz Neuromuscular Centre, Developmental Neuroscience Research and 
      Teaching Department, UCL Great Ormond Street Institute of Child Health, NIHR 
      Great Ormond Street Hospital Biomedical Research Centre & Great Ormond Street 
      Hospital NHS Foundation Trust, UCL Great Ormond Street Institute of Child Health, 
      London, UK.
CN  - Paediatric UK Risdiplam EAMS Working Group
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - J Neuromuscul Dis
JT  - Journal of neuromuscular diseases
JID - 101649948
RN  - 76RS4S2ET1 (Risdiplam)
RN  - 0 (Pyrimidines)
RN  - 0 (Azo Compounds)
SB  - IM
MH  - Humans
MH  - Child
MH  - Infant, Newborn
MH  - Infant
MH  - Child, Preschool
MH  - Adolescent
MH  - United Kingdom
MH  - *Muscular Atrophy, Spinal/drug therapy/genetics
MH  - *Spinal Muscular Atrophies of Childhood/drug therapy
MH  - Pyrimidines/adverse effects
MH  - *Azo Compounds
PMC - PMC10977425
OTO - NOTNLM
OT  - Spinal muscular atrophy
OT  - adverse events
OT  - risdiplam
OT  - safety
OT  - treatment
COIS- GB is PI of clinical trials Sponsored by Roche, Novartis, Sarepta, Pfizer, NS 
      Pharma, Reveragen, Scholar Rock, and has received speaker and/or consulting fees 
      from Sarepta, PTC Therapeutics, Pfizer, Biogen, Novartis Gene Therapies, Inc. 
      (AveXis), and Roche, and grants from Sarepta, Roche and Novartis Gene Therapies. 
      NC has received sponsorship to attend conferences from Roche AC has led symposia 
      and participated in Ad boards for Roche and Biogen in the last 3 years and is PI 
      for the Sapphire Study (Scholar Rock). EW has undertaken consultancy for Roche 
      and sponsored to attend meetings IH has received Honoraria from Roche DP is PI 
      for Jewelfish study at UHB Birmingham and has been on temporary advisory board 
      for Roche and sponsored to attend meetings by Roche. TW has been on an advisory 
      board for Roche MS is involved as principal investigator in clinical trials from 
      Roche, Biogen and Novartis. Receiving honoraria for the participation in 
      Scientific Advisory boards and teaching initiatives for Roche, Novartis and 
      Biogen. Co- principal investigator of the SMA REACH UK network, currently funded 
      by Biogen and Roche PM, SS, CM, MI, GC AM, GA have no conflicts of interest.
EDAT- 2024/01/08 12:42
MHDA- 2024/03/12 06:42
PMCR- 2024/03/28
CRDT- 2024/01/08 10:33
PHST- 2024/03/12 06:42 [medline]
PHST- 2024/01/08 12:42 [pubmed]
PHST- 2024/01/08 10:33 [entrez]
PHST- 2024/03/28 00:00 [pmc-release]
AID - JND230162 [pii]
AID - 10.3233/JND-230162 [doi]
PST - ppublish
SO  - J Neuromuscul Dis. 2024;11(2):361-368. doi: 10.3233/JND-230162.