TY - JOUR
T1 - Risdiplam in Patients Previously Treated with Other Therapies for Spinal Muscular Atrophy
T2 - An Interim Analysis from the JEWELFISH Study
AU - the JEWELFISH Study Group
AU - Chiriboga, Claudia A.
AU - Bruno, Claudio
AU - Duong, Tina
AU - Fischer, Dirk
AU - Mercuri, Eugenio
AU - Kirschner, Janbernd
AU - Kostera-Pruszczyk, Anna
AU - Jaber, Birgit
AU - Gorni, Ksenija
AU - Kletzl, Heidemarie
AU - Carruthers, Imogen
AU - Martin, Carmen
AU - Warren, Francis
AU - Scalco, Renata S.
AU - Wagner, Kathryn R.
AU - Muntoni, Francesco
N1 - Funding Information:
The authors thank Michelle B. Kim, PhD, of MediTech Media for providing medical writing support, which was funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland in accordance with Good Publication Practice (GPP3) guidelines ( http://www.ismpp.org/gpp3 ).
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/4
Y1 - 2023/4
N2 - Introduction: Risdiplam is a survival of motor neuron 2 (SMN2) splicing modifier for the treatment of patients with spinal muscular atrophy (SMA). The JEWELFISH study (NCT03032172) was designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of risdiplam in previously treated pediatric and adult patients with types 1–3 SMA. Here, an analysis was performed after all patients had received at least 1 year of treatment with risdiplam. Methods: Patients with a confirmed diagnosis of 5q-autosomal recessive SMA between the ages of 6 months and 60 years were eligible for enrollment. Patients were previously enrolled in the MOONFISH study (NCT02240355) with splicing modifier RG7800 or treated with olesoxime, nusinersen, or onasemnogene abeparvovec. The primary objectives of the JEWELFISH study were to evaluate the safety and tolerability of risdiplam and investigate the PK after 2 years of treatment. Results: A total of 174 patients enrolled: MOONFISH study (n = 13), olesoxime (n = 71 patients), nusinersen (n = 76), onasemnogene abeparvovec (n = 14). Most patients (78%) had three SMN2 copies. The median age and weight of patients at enrollment was 14.0 years (1–60 years) and 39.1 kg (9.2–108.9 kg), respectively. About 63% of patients aged 2–60 years had a baseline total score of less than 10 on the Hammersmith Functional Motor Scale–Expanded and 83% had scoliosis. The most common adverse event (AE) was upper respiratory tract infection and pyrexia (30 patients each; 17%). Pneumonia (four patients; 2%) was the most frequently reported serious AE (SAE). The rates of AEs and SAEs per 100 patient-years were lower in the second 6-month period compared with the first. An increase in SMN protein was observed in blood after risdiplam treatment and was comparable across all ages and body weight quartiles. Conclusions: The safety and PD of risdiplam in patients who were previously treated were consistent with those of treatment-naïve patients.
AB - Introduction: Risdiplam is a survival of motor neuron 2 (SMN2) splicing modifier for the treatment of patients with spinal muscular atrophy (SMA). The JEWELFISH study (NCT03032172) was designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of risdiplam in previously treated pediatric and adult patients with types 1–3 SMA. Here, an analysis was performed after all patients had received at least 1 year of treatment with risdiplam. Methods: Patients with a confirmed diagnosis of 5q-autosomal recessive SMA between the ages of 6 months and 60 years were eligible for enrollment. Patients were previously enrolled in the MOONFISH study (NCT02240355) with splicing modifier RG7800 or treated with olesoxime, nusinersen, or onasemnogene abeparvovec. The primary objectives of the JEWELFISH study were to evaluate the safety and tolerability of risdiplam and investigate the PK after 2 years of treatment. Results: A total of 174 patients enrolled: MOONFISH study (n = 13), olesoxime (n = 71 patients), nusinersen (n = 76), onasemnogene abeparvovec (n = 14). Most patients (78%) had three SMN2 copies. The median age and weight of patients at enrollment was 14.0 years (1–60 years) and 39.1 kg (9.2–108.9 kg), respectively. About 63% of patients aged 2–60 years had a baseline total score of less than 10 on the Hammersmith Functional Motor Scale–Expanded and 83% had scoliosis. The most common adverse event (AE) was upper respiratory tract infection and pyrexia (30 patients each; 17%). Pneumonia (four patients; 2%) was the most frequently reported serious AE (SAE). The rates of AEs and SAEs per 100 patient-years were lower in the second 6-month period compared with the first. An increase in SMN protein was observed in blood after risdiplam treatment and was comparable across all ages and body weight quartiles. Conclusions: The safety and PD of risdiplam in patients who were previously treated were consistent with those of treatment-naïve patients.
KW - Evrysdi
KW - Pharmacodynamics
KW - Risdiplam
KW - Safety
KW - Spinal muscular atrophy
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U2 - 10.1007/s40120-023-00444-1
DO - 10.1007/s40120-023-00444-1
M3 - Article
C2 - 36780114
AN - SCOPUS:85148078301
SN - 2193-8253
VL - 12
SP - 543
EP - 557
JO - Neurology and Therapy
JF - Neurology and Therapy
IS - 2
ER -