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Arsa-Cel, A Lentiviral Haematopoietic Stem and Progenitor Cell Gene Therapy For The Treatment of Metachromatic Leukodystrophy: Clinical Outcomes From 38 Patients

Objectives: MLD is a fatal demyelinating lysosomal disease resulting from arylsulfatase A (ARSA) deficiency. Atidarsagene autotemcel (“arsa-cel”) is a haematopoietic stem and progenitor cell- based gene therapy consisting of autologous CD34+ cells transduced ex vivo with a lentiviral vector encoding for the human ARSA gene. Primary objectives were safety and efficacy of arsa-cel.

Methods: Thirty-eight patients with early-onset forms of MLD (20 late-infantile, 18 early-juvenile were treated with arsa-cel. Key endpoints were compared to an untreated natural history cohort.

Results: Of 38 patients treated, 35 are alive (2 died from disease progression, 1 from cerebral stroke, all unrelated to treatment). There were no treatment-related mortality or serious adverse events, no malignancies, no abnormal clonal expansion, and no evidence of replication-competent lentivirus. The majority of patients treated before symptom onset displayed long-term stabilisation of motor function, with many maintaining the ability to walk, and normal cognitive development.

Conclusions: Data from 38 early-onset MLD patients with up to 8.85 years of follow-up demonstrated that arsa-cel was generally well-tolerated and effective in modifying the disease course of early-onset MLD patients. Atidarsagene autotemcel (Libmeldy™) was approved by the European Medicines Agency in 2020 and is indicated for the treatment of children with late-infantile or early-juvenile forms, without clinical manifestations of the disease and in children with the early-juvenile form, with early clinical manifestations of the disease, who still have the ability to walk independently and before the onset of cognitive decline. Five European centres have been qualified to date to treat patients with arsa-cel.

Francesca Fumagalli
IRCCS Ospedale San Raffaele
Italy

Valeria Calbi
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute
Italy

Alberto Zambon
IRCCS San Raffaele Scientific Institute
Italy

Vera Gallo
IRCCS San Raffaele Scientific Institute
Italy

Cristina Baldoli
IRCCS San Raffaele Scientific Institute
Italy

Federica Cugnata
Vita-Salute San Raffaele University
Italy

Paola M.v. Rancoita
IRCCS San Raffaele Scientific Institute
Italy

Fabiola De Mattia
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute
Italy

Elena Fratini
IRCCS San Raffaele Scientific Institute
Italy

Salvatore Recupero
IRCCS San Raffaele Scientific Institute
Italy

Francesca Ferrua
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute
Italy

Federica Barzaghi
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute
Italy

Maria Pia Cicalese
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute
Italy

Maddalena Migliavacca
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute
Italy

Francesca Tucci
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute
Italy

Francesca Ciotti
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute
Italy

Maddalena Fraschini
IRCCS San Raffaele Scientific Institute
Italy

Marina Sarzana
IRCCS San Raffaele Scientific Institute
Italy

Stefano Scarparo
IRCCS San Raffaele Scientific Institute
Italy

Paolo Silvani
IRCCS San Raffaele Scientific Institute
Italy

Sara Locatelli
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute
Italy

Alessandra Clerici
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute
Italy

Gigliola Antonioli
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute
Italy

Mara Sangalli
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute
Italy

Stefano Zancan
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET)
Italy

Andrea Calabria
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET)
Italy

Eugenio Montini
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET)
Italy

Giada Farinelli
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET)
Italy

Francesca Morena
University of Perugia
Italy

Jesus Segovia
Orchard Therapeutics (Europe) Limited
United Kingdom

Laetitia C. Schwab
Orchard Therapeutics (Europe) Limited
United Kingdom

Gerald Downey
Orchard Therapeutics (Europe) Limited
United Kingdom

Mirko M. Essing
Orchard Therapeutics (Europe) Limited
United Kingdom

Michela Gabaldo
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute
Italy

Sabata Martino
University of Perugia
Italy

Clelia Di Serio
Vita-Salute San Raffaele University
Italy

Fabio Ciceri
Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute
Italy

Massimo Filippi
Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute
Italy

Maria Sessa
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, ASST Papa Giovanni XXIII
Italy

Maria Grazia Natali Sora
IRCCS San Raffaele Scientific Institute
Italy

Maria Ester Bernardo
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute
Italy

Luigi Naldini
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University
Italy

Alessandra Biffi
Padua University and Hospital, Dana Farber/Boston Children’s Cancer and Blood Disorders Center
Italy

Alessandro Aiuti
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University
Italy

 


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