EClinicalMedicine (May 2023)
Onasemnogene abeparvovec in spinal muscular atrophy: predictors of efficacy and safety in naïve patients with spinal muscular atrophy and following switch from other therapiesResearch in context
- Marika Pane,
- Beatrice Berti,
- Anna Capasso,
- Giorgia Coratti,
- Antonio Varone,
- Adele D’Amico,
- Sonia Messina,
- Riccardo Masson,
- Valeria Ada Sansone,
- Maria Alice Donati,
- Caterina Agosto,
- Claudio Bruno,
- Federica Ricci,
- Antonella Pini,
- Delio Gagliardi,
- Massimiliano Filosto,
- Stefania Corti,
- Daniela Leone,
- Concetta Palermo,
- Roberta Onesimo,
- Roberto De Sanctis,
- Martina Ricci,
- Ilaria Bitetti,
- Maria Sframeli,
- Claudia Dosi,
- Emilio Albamonte,
- Chiara Ticci,
- Noemi Brolatti,
- Enrico Bertini,
- Richard Finkel,
- Eugenio Mercuri,
- Maria Carmela Pera,
- Chiara Bravetti,
- Marco Piastra,
- Orazio Genovese,
- Gianpaolo Cicala,
- Nicola Forcina,
- Sara Carnicella,
- Giulia Stanca,
- Michele Sacchini,
- Michela Catteruccia,
- Michele Tosi,
- Renato Cutrera,
- Claudio Chierchi,
- Maria Beatrice Chiarini,
- Francesca Salmin,
- Marina Pedemonte,
- Alessandra Govoni,
- Irene Mizzoni,
- Simone Morando,
- Riccardo Zanin,
- Enrica Rolle,
- Eleonora Salomon,
- Melania Giannotta,
- Gaia Scarpini,
- Antonio Toscano,
- Eloisa Gitto,
- Roberto Materia,
- Rossella D’Alessandro
Affiliations
- Marika Pane
- Paediatric Neurology, Catholic University, Rome, Italy; Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Beatrice Berti
- Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Anna Capasso
- Paediatric Neurology, Catholic University, Rome, Italy; Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Giorgia Coratti
- Paediatric Neurology, Catholic University, Rome, Italy; Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Antonio Varone
- Department of Neurosciences, Paediatric Neurology, Santobono-Pausilipon Children's Hospital, Naples, Italy
- Adele D’Amico
- Unit of Neuromuscular and Neurodegenerative Disorders, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy
- Sonia Messina
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
- Riccardo Masson
- Fondazione IRCCS Istituto Neurologico Carlo Besta Developmental Neurology Unit, Milan, Italy
- Valeria Ada Sansone
- Neurorehabilitation Unit, Centro Clinico Nemo, Niguarda Hospital, University of Milan, Milano, Italy
- Maria Alice Donati
- Metabolic and Muscular Unit, Meyer Children's Hospital IRCCS, Florence, Italy
- Caterina Agosto
- Dipartimento di Salute della Donna e del Bambino, Università di Padova, Padua, Italy
- Claudio Bruno
- Center of Myology and Neurodegenerative Disorders, IRCCS Istituto Giannina Gaslini, Genoa, Italy
- Federica Ricci
- AOU Città della Salute e della Scienza di Torino, Presidio OIRM (SC Neuropsichiatria Infantile), Turin, Italy
- Antonella Pini
- Neuromuscular Pediatric Unit, IRCCS Istituto delle Scienze Neurologiche di Bologna-UOC Neuropsichiatria dell’Età Pediatrica, Bologna, Italy
- Delio Gagliardi
- Pediatric Neurology Unit, Pediatric Hospital ''Giovanni XXIII'', Bari, Italy
- Massimiliano Filosto
- Department of Clinical and Experimental Sciences, NeMO-Brescia Clinical Center for Neuromuscular Diseases, University of Brescia; Brescia, Italy
- Stefania Corti
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milan, Milan, Italy
- Daniela Leone
- Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Concetta Palermo
- Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Roberta Onesimo
- Rare Disease Unit, Pediatric Unit - Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Roberto De Sanctis
- Paediatric Neurology, Catholic University, Rome, Italy; Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Martina Ricci
- Paediatric Neurology, Catholic University, Rome, Italy; Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Ilaria Bitetti
- Department of Neurosciences, Paediatric Neurology, Santobono-Pausilipon Children's Hospital, Naples, Italy
- Maria Sframeli
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
- Claudia Dosi
- Fondazione IRCCS Istituto Neurologico Carlo Besta Developmental Neurology Unit, Milan, Italy
- Emilio Albamonte
- Neurorehabilitation Unit, Centro Clinico Nemo, Niguarda Hospital, University of Milan, Milano, Italy
- Chiara Ticci
- Metabolic and Muscular Unit, Meyer Children's Hospital IRCCS, Florence, Italy
- Noemi Brolatti
- Center of Myology and Neurodegenerative Disorders, IRCCS Istituto Giannina Gaslini, Genoa, Italy
- Enrico Bertini
- Unit of Neuromuscular and Neurodegenerative Disorders, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy
- Richard Finkel
- Department of Paediatric Medicine, Center for Experimental Neurotherapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA
- Eugenio Mercuri
- Paediatric Neurology, Catholic University, Rome, Italy; Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Corresponding author. Paediatric Neurology Unit, Policlinico Gemelli, Largo Gemelli, Roma, 00168 Italy.
- Maria Carmela Pera
- Chiara Bravetti
- Marco Piastra
- Orazio Genovese
- Gianpaolo Cicala
- Nicola Forcina
- Sara Carnicella
- Giulia Stanca
- Michele Sacchini
- Michela Catteruccia
- Michele Tosi
- Renato Cutrera
- Claudio Chierchi
- Maria Beatrice Chiarini
- Francesca Salmin
- Marina Pedemonte
- Alessandra Govoni
- Irene Mizzoni
- Simone Morando
- Riccardo Zanin
- Enrica Rolle
- Eleonora Salomon
- Melania Giannotta
- Gaia Scarpini
- Antonio Toscano
- Eloisa Gitto
- Roberto Materia
- Rossella D’Alessandro
- Journal volume & issue
-
Vol. 59
p. 101997
Abstract
Summary: 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.
