Published 2023
| Version v1
Publication
Onasemnogene abeparvovec in spinal muscular atrophy: predictors of efficacy and safety in naïve patients with spinal muscular atrophy and following switch from other therapies
Creators
- 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.
- Finkel R.
- Mercuri E.
- 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.
Contributors
Others:
- 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.
- Finkel, R.
- Mercuri, E.
- 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.
Description
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.
Additional details
Identifiers
- URL
- https://hdl.handle.net/11567/1146836
- URN
- urn:oai:iris.unige.it:11567/1146836
Origin repository
- Origin repository
- UNIGE