Efficacy and safety of onasemnogene abeparvovec in children with spinal muscular atrophy type 1: real-world evidence from 6 infusion centres in the United Kingdom.
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Gowda Vasantha, Atherton Mark, Murugan Archana, Servais Laurent, Sheehan Jennie, Standing Emma, Manzur Adnan, Scoto Mariacristina, Baranello Giovanni, Munot Pinki, McCullagh Gary, Willis Tracey, Tirupathi Sandya, Horrocks Iain, Dhawan Anil, Eyre Michael, Vanegas Maria, Fernandez-Garcia Miguel A, Wolfe Amy, Pinches Laura, Illingworth Marjorie, Main Marion, Abbott Lianne, Smith Hayley, Milton Emily, D'Urso Sarah, Vijayakumar Kayal, Marco Silvia Sanchez, Warner Sinead, Reading Emily, Douglas Isobel, Muntoni Francesco, Ong Min, Majumdar Anirban, Hughes Imelda, Jungbluth Heinz, Wraige Elizabeth
Аннотация
METHODS: This observational cohort study used data from patients with genetically confirmed SMA type 1 treated with OA between May 2021 and January 2023, at 6 infusion centres in the United Kingdom. Functional outcomes were assessed using age-appropriate functional scales. Safety analyses included review of liver function, platelet count, cardiac assessments, and steroid requirements.
FINDINGS: Ninety-nine patients (45 SMA therapy-naïve) were treated with OA (median age at infusion: 10 [range, 0.6-89] months; median weight: 7.86 [range, 3.2-20.2] kg; duration of follow-up: 3-22 months). After OA infusion, mean ± SD change in CHOP-INTEND score was 11.0 ± 10.3 with increased score in 66/78 patients (84.6%); patients aged <6 months had a 13.9 points higher gain in CHOP-INTEND score than patients ≥2 years (95% CI, 6.8-21.0; P < 0.001). Asymptomatic thrombocytopenia (71/99 patients; 71.7%), asymptomatic troponin-I elevation (30/89 patients; 33.7%) and transaminitis (87/99 patients; 87.9%) were reported. No thrombotic microangiopathy was observed. Median steroid treatment duration was 97 (range, 28-548) days with dose doubled in 35/99 patients (35.4%). There were 22.5-fold increased odds of having a transaminase peak >100 U/L (95% CI, 2.3-223.7; P = 0.008) and 21.2-fold increased odds of steroid doubling, as per treatment protocol (95% CI, 2.2-209.2; P = 0.009) in patients weighing ≥13.5 kg versus <8.5 kg. Weight at infusion was positively correlated with steroid treatment duration (r = 0.43; P < 0.001). Worsening transaminitis, despite doubling of oral prednisolone, led to treatment with intravenous methylprednisolone in 5 children. Steroid-sparing immunosuppressants were used in 5 children to enable steroid weaning. Two deaths apparently unrelated to OA were reported.
INTERPRETATION: OA led to functional improvements and was well tolerated with no persistent clinical complications, including in older and heavier patients.
FUNDING: Novartis Innovative Therapies AG provided a grant for independent medical writing services.