Onasemnogene abeparvovec in spinal muscular atrophy: predictors of efficacy and safety in naïve patients with spinal muscular atrophy and following switch from other therapies
Articolo
Data di Pubblicazione:
2023
Citazione:
Onasemnogene abeparvovec in spinal muscular atrophy: predictors of efficacy and safety in naïve patients with spinal muscular atrophy and following switch from other therapies / M. Pane, B. Berti, A. Capasso, G. Coratti, A. Varone, A. D'Amico, S. Messina, R. Masson, V.A. Sansone, M.A. Donati, C. Agosto, C. Bruno, F. Ricci, A. Pini, D. Gagliardi, M. Filosto, S. Corti, D. Leone, C. Palermo, R. Onesimo, R. De Sanctis, M. Ricci, I. Bitetti, M. Sframeli, C. Dosi, E. Albamonte, C. Ticci, N. Brolatti, E. Bertini, R. Finkel, E. Mercuri. - In: ECLINICALMEDICINE. - ISSN 2589-5370. - 59:(2023 May), pp. 101997.1-101997.13. [10.1016/j.eclinm.2023.101997]
Abstract:
Background: Efficacy and safety of onasemnogene abeparvovec (OA) for Spinal Muscular Atrophy infants under 7 months and <8.5 kg has been reported in clinical trials. This study examines efficacy and safety predictors in a wide age (22 days-72 months) and weight (3.2-17 kg) range, also including patients previously treated with other drugs. Methods: 46 patients were treated for 12 months between January 2020 and March 2022. Safety profile was also available for another 21 patients with at least 6 month follow-up after OA infusion. 19/67 were treatment naïve when treated with OA. Motor function was measured with the CHOP-INTEND. Findings: CHOP-INTEND changes varied among age groups. Baseline score and age at OA treatment best predicted changes. A mixed model post-hoc analysis showed that in patients treated before the age of 24 months the CHOP-INTEND changes were already significant 3 months after OA while in those treated after the age of 24 months the difference was only significant 12 months after OA. Adverse events occurred in 51/67. The risk for elevated transaminases serum levels was higher in older patients. This was also true for weight and for pre-treatment with nusinersen when analysed individually. A binomial negative regression analysis showed that only age at OA treatment had a significant effect on the risk of elevated transaminases. Interpretation: Our paper describes OA 12-month follow-up showing efficacy across various age and weight groups not targeted by clinical trials. The study identifies prognostic factors for safety and efficacy in treatment selection.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Follow-up; Gene therapy; Longitudinal; Safety; Spinal muscular atrophy
Elenco autori:
M. Pane, B. Berti, A. Capasso, G. Coratti, A. Varone, A. D'Amico, S. Messina, R. Masson, V.A. Sansone, M.A. Donati, C. Agosto, C. Bruno, F. Ricci, A. Pini, D. Gagliardi, M. Filosto, S. Corti, D. Leone, C. Palermo, R. Onesimo, R. De Sanctis, M. Ricci, I. Bitetti, M. Sframeli, C. Dosi, E. Albamonte, C. Ticci, N. Brolatti, E. Bertini, R. Finkel, E. Mercuri
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