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. Funding: None.
Pane, M., Berti, B., Capasso, A., Coratti, G., Varone, A., D'Amico, A., Messina, S., Masson, R., Sansone, V. A., Donati, M. A., Agosto, C., Bruno, C., Ricci, F., Pini, A., Gagliardi, D., Filosto, M., Corti, S., Leone, D., Palermo, C., Onesimo, R., De Sanctis, R., Ricci, M., Bitetti, I., Sframeli, M., Dosi, C., Albamonte, E., Ticci, C., Brolatti, N., Bertini, E. S., Finkel, R., Mercuri, E. M., Pera, M. C., Bravetti, C., Piastra, M., Genovese, O., Cicala, G., Forcina, N., Carnicella, S., Stanca, G., Sacchini, M., Catteruccia, M., Tosi, M., Cutrera, R., Chierchi, C., Chiarini, M. B., Salmin, F., Pedemonte, M., Govoni, A., Mizzoni, I., Morando, S., Zanin, R., Rolle, E., Salomon, E., Giannotta, M., Scarpini, G., Toscano, A., Gitto, E., Materia, R., D'Alessandro, R., Onasemnogene abeparvovec in spinal muscular atrophy: predictors of efficacy and safety in naïve patients with spinal muscular atrophy and following switch from other therapies, <<ECLINICALMEDICINE>>, 2023; 59 (MAY): N/A-N/A. [doi:10.1016/j.eclinm.2023.101997] [https://hdl.handle.net/10807/235648]
Onasemnogene abeparvovec in spinal muscular atrophy: predictors of efficacy and safety in naïve patients with spinal muscular atrophy and following switch from other therapies
Pane, Marika;Capasso, Anna;Coratti, Giorgia;Onesimo, Roberta;De Sanctis, Roberto;Ricci, Martina;Bertini, Enrico Silvio;Mercuri, Eugenio Maria;Pera, Maria Carmela;Piastra, Marco;Genovese, Orazio;Cicala, Gianpaolo;Cutrera, Renato;
2023
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. Funding: None.
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