FDA Approves Atidarsagene Autotemcel for Treatment of MLD in Pediatric Patients


This approval makes atidarsagene autotemcel the only therapy to be approved in the US for early-symptomatic early juvenile metachromatic leukodystrophy.

FDA approval stamp -- Image credit: Olivier Le Moal | stock.adobe.com

Image credit: Olivier Le Moal | stock.adobe.com

The FDA has approved atidarsagene autotemcel (Lenmeldy; Orchard Therapeutics) for the treatment of children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ), or early symptomatic early juvenile (ESEJ), which is collectively referred to as early-onset metachromatic leukodystrophy (MLD). This drug is currently the only approved therapy in the US for the treatment of PSLI, PSEJ, or ESEJ MLD.1

Atidarsagene autotemcel, formerly called OTL-200, is an autologous hematopoietic stem cell-based gene therapy that corrects the underlying genetic cause of MLD by inserting at least one functional copy of the ARSA gene ex vivo into the patient’s hematopoietic stem cells. The genetically repaired cells are then infused back into the patient, and they differentiate into multiple cell types once engrafted. Some of the cells travel across the blood-brain barrier into the central nervous system and express the functional enzyme, restoring function to stop or slow disease progression. Previously, the FDA granted atidarsagene autotemcel priority review in September 2023, as well as rare pediatric disease and regenerative medicine advanced therapy designations.1

“The FDA approval of [atidarsagene autotemcel] opens up tremendous new possibilities for children in the US with early-onset MLD who previously had no treatment options beyond supportive and end-of-life care,” said Bobby Gaspar, MD, PhD, co-founder and chief executive officer of Orchard Therapeutics, in a press release. “MLD is a rapidly progressing, life-limiting and ultimately fatal rare disease that has a devastating impact on afflicted children and their families.”1

The FDA approval comes after positive data from 2 single-arm, open-label clinical studies which assessed the efficacy of atidarsagene autotemcel when treating 37 pediatric patients with early-onset MLD. After more than 12 years of follow-up in the patients who were treated the earliest (median 6.76 years), treatment with atidarsagene autotemcel appeared to both improve overall survival and preserve motor functions and cognitive skills in most late-infantile patients with MLD and early juvenile patients. Untreated patients past this age demonstrated severe cognitive and motor impairments.1

According to the investigators, the most common non-laboratory adverse events (incidence: ≥ 10%) were febrile neutropenia (85%), stomatitis (77%), respiratory tract infections (54%), rash (33%), device-related infections (31%), viral infections (28%), pyrexia (21%), gastroenteritis (21%), and hepatomegaly (18%). In addition, common laboratory abnormalities were elevated D-dimer (67%), neutropenia (28%), and elevated liver enzymes (23%).1

“This is a momentous occasion and I commend the FDA for recognizing the clinical impact [atidarsagene autotemcel] has on this cruel disease,” said Barbara Burton, MD, attending physician of genetics, genomics and metabolism at the Ann & Robert H. Lurie Children’s Hospital of Chicago, in the press release.1

A prior study, which led to the FDA accepting a biologics license application for atidarsagene autotemcel, had demonstrated both efficacy and safety in patients who received the treatment. According to the findings, atidarsagene autotemcel had resulted in both statistically significant and clinically meaningful improvement in sMFS in PSLI, PSEJ, and ESEJ MLD. In addition, 17 or 18 PSLI patients, 7 surviving PSEJ, and 6 of 9 surviving ESEJ patients had continued to acquire cognitive skills as expected for their age.2

“With this approval, we are now one significant step closer to ensuring future generations of children, families, and health care professionals no longer need to experience first-hand the terrible manifestations this disease has on untreated patients,” said Burton in the press release.1

1. Orchard Therapeutics. Orchard Therapeutics Receives FDA Approval of Lenmeldy™ (atidarsagene autotemcel), the Only Therapy for Eligible Children with Early-onset Metachromatic Leukodystrophy in the U.S. News release. March 18, 2024. Accessed March 19, 2024. https://ir.orchard-tx.com/news-releases/news-release-details/orchard-therapeutics-receives-fda-approval-lenmeldytm
2. Orchard Therapeutics. Orchard Therapeutics Announces Presentation of Data Comprising the Clinical Package for the OTL-200 BLA in MLD at the SSIEM Annual Symposium 2023. News release. August 31, 2023. Accessed March 19, 2024. https://ir.orchard-tx.com/news-releases/news-release-details/orchard-therapeutics-announces-presentation-data-comprising
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