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.
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, 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., et al.. - In: ECLINICALMEDICINE. - ISSN 2589-5370. - 59:MAY(2023), pp. 101997.N/A-101997.N/A. [10.1016/j.eclinm.2023.101997]
Onasemnogene abeparvovec in spinal muscular atrophy: predictors of efficacy and safety in naïve patients with spinal muscular atrophy and following switch from other therapies
Pera M. C.;
2023-01-01
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
