Long term data from 2 clinical trials and expanded access programs were presented at WORLDSymposium 2023.
Long-term data of up to 11 years of follow-up on the gene-edited cell therapy atidarsagene autotemcel (arsa-cel; Orchard Therapeutics) has demonstrated a continued favorable risk/benefit profile inpatients with pre-symptomatic (PS) late-infantile and early-juvenile (EJ), and early-symptomatic (ES) EJ metachromatic leukodystrophy (MLD).1
The updated data, from 2 clinical trials (NCT01560182, NCT03392987) conducted at San Raffaele Telethon Institute for Gene Therapy in Milan, Italy, and expanded access programs, were presented at the WORLDSymposium 2023, held February 22-26, in Orlando, Florida, by Francesca Fumagalli, MD, neurologist, IRCCS Ospedale San Raffaele.
The investigators analyzed data from 39 patients (PSLI, 18; PSEJ, 8; ESEJ, 11) across studies compared to an untreated natural history cohort of 43 patients (LI, 26; EJ, 17) with early-onset MLD at the same center. All patients achieved hematological recovery, stable engraftment, and restoration of arylsulfatase A (ARSA) enzyme to normal or supranormal levels by 3 months in peripheral blood mononuclear cells and by 3 to 12 months in cerebrospinal fluid.
"Most treated patients maintained normal or near-normal cognitive development, as shown by performance age equivalents. In contrast, untreated natural history patients lost cognitive skills previously acquired during the phase of normal development early in their disease course and progressed to a severely impaired state,” Fumagalli and colleagues wrote in their poster.1
READ MORE: In Vivo Gene Therapy Candidate for Metachromatic Leukodystrophy in Development
Almost all (n = 17/18) patients with PSLI MLD and all surviving patients with PSEJ MLD maintained the ability to walk. Most (7/9) patients with ESEJ MLD maintained the ability to sit without support and/or crawl/roll.All but 2 patients had preserved cognitive function normal or near-normal range compared to the severe decline seen in natural history.
Arsa-cel was well-tolerated, with no treatment-related deaths or serious adverse events (AEs). Two patients with ESEJ MLD died due to rapid disease progression and another with PSEJ MLD died due to ischemic cerebral infarction. Most AEs were related to disease progression or busulfan conditioning and the only treatment-related AEs were anti-ARSA antibodies developed in 6 patients, 5 events resolved spontaneously or with minimal rituximab treatment and 1 event is ongoing but has not impacted clinical outcomes. One patient had prolonged anemia and thrombocytopenia and required an infusion of unmanipulated back-up cells. There were no cases of malignancy, clonal expansion, or replication competent lentivirus.
“Arsa-cel preserves motor development in PSLI and PSEJ MLD patients, with 24 of 25 surviving patients maintaining the ability towalk, and stabilizes or slows down motor decline in ESEJ MLD patients compared with natural history,” Fumagalli and colleagues wrote.1
Arsa-cel is approved in the EU under the name Libmeldy, where it is being distributed to children under a limited distribution model that includes 5 centers of excellence trained as qualified treatment centers (QTC) across the continent. The model was presented in a poster at the 2023 Tandem Meetings |Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, held in Orlando, Florida, February 15-19, 2023.2 CGTLive spoke with Madeleine Powys, MBBS, a locum consultant of pediatric BMT and leukemia at Royal Manchester Children’s Hospital, the only QTC for arsa-cel in the United Kingdom, to learn more about her experience delivering arsa-cel to children and challenges that remain.
“Because these are rare diseases, it's important that you have centers of excellence that are qualified treatment centers where there's clinical, nursing, and laboratory expertise... There's been an enormous amount of effort put into training of all the staff on the various complex steps that need to occur to make sure that the product is safely collected, manufactured and delivered into our patients,” Powys told CGTLive.
Click here to read more coverage of WORLDSymposium 2023.