FDA Approves First Gene Therapy for Pediatric MLD from Orchard Therapeutics, and AGC Biologics Tapped to Manufacture It

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Orchard Therapeutics’ Lenmeldy (atidarsagene autotemcel) marks the first gene therapy approved in the US for treating children with metachromatic leukodystrophy.

On March 18, 2024, FDA granted approval to Orchard Therapeutics for Lenmeldy (atidarsagene autotemcel), which marks the first FDA-approved gene therapy for treating children with pre-symptomatic late infantile, pre-symptomatic early juvenile, or early symptomatic early juvenile metachromatic leukodystrophy (MLD) in the United States. Following the approval, AGC Biologics announced that it will be manufacturing the therapy at its Milan, Italy, site.

According to a FDA press release, MLD is a debilitating, rare genetic disease that affects the brain and nervous system caused by a deficiency of the arylsulfatase A (ARSA) enzyme. This deficiency leads to a buildup of sulfatides in the cells, which causes damage to the central and peripheral nervous system, leading to a loss of motor and cognitive function and early death. MLD is estimated to affect one in every 40,000 individuals in the US, and there is no cure for it. Currently, treatment typically focuses on supportive care and management of symptoms.

“This is the first FDA-approved treatment option for children who have this rare genetic disease,” said Peter Marks, director of FDA’s Center for Biologics Evaluation and Research (CBER), in the press release. “We remain committed to advancing scientific and regulatory principles that enable the efficient development and review of safe, effective and innovative products that have the potential to change patients’ lives.”

Lenmeldy, derived from the patient’s own hematopoietic stem cells (HSCs), is a one-time, individualized single-dose infusion. The patient’s HSCs are collected and genetically modified to include functional copies of the ARSA gene. The modified cells are then transplanted back into the patient where they engraft within the bone marrow and supply the body with ARSA enzyme-producing myeloid cells. The enzyme helps break down the build-up of sulfatides and may stop the progression of MLD. Prior to treatment with Lenmeldy, patients must undergo high-dose chemotherapy to removes cells from the bone marrow that can then be replaced with the modified HSCs, according to the FDA release.

“This approval represents important progress in the advancement and availability of effective treatments, including gene therapies, for rare diseases,” said Nicole Verdun, director of the Office of Therapeutic Products in CBER.

The application for Lenmeldy received priority review, orphan drug, rare pediatric disease, and regenerative medicine advanced therapy designations.


Clearance for manufacturing

Following Lenmeldy’s approval, contract development and manufacturing organization (CDMO), AGC Biologics, announced that its Milan, Italy, site has received clearances from both US and European regulators and can now use approved commercial processes to supply patients with the gene therapy. The company will begin commercial manufacturing for the lentiviral vector and genetically modified cell drug product (DP) for Lenmeldy at the site.

“It is wonderful to see Orchard Therapeutics reach this goal. This accomplishment is a strong proof point of our commitment at AGC Biologics to collaborating directly with developers to meet rigorous regulatory standards and achieve the best possible results for our partners,” said Patricio Massera, CEO, AGC Biologics, in a March 18, 2024 company press release.

According to the company press release, the Milan site has become the only CDMO site to receive FDA clearance to commercially produce this gene therapy for US patients. AGC Biologics stated in the release that the FDA approval is “the culmination of a partnership that started in 2018 with Orchard Therapeutics, which also includes guiding the product through commercial approval by the European Commission (EC) in 2021 [under the European brand name Libmeldy] (1). AGC Biologics’ Milan site is uniquely connected to this product’s full lifecycle, as the facility and our scientific teams partnered with each company that owned this treatment’s IP [intellectual property] over the [p]ast 20 years to help advance it from research and development stages to this DP commercial milestone.”

Luca Alberici, general manager of AGC Biologics Milan, stated in the release, “We congratulate Orchard for reaching this important stage. Our team has had the privilege of supplying every clinical milestone for Lenmeldy and are glad to see it reach FDA approval. I am proud of the work of the Milan team.This demonstrates our unique ability to collaborate on technical processes to deliver groundbreaking treatments to patients worldwide. This approval makes our site one of the rare few in the viral vector and genetically modified cells field that has commercial manufacturing authorization from two of the world’s leading regulatory authorities."

"AGC Biologics has played a pivotal role as a strategic partner throughout the clinical development and commercial scale-up of atidarsagene autotemcel, which helped facilitate regulatory approvals in Europe and the US," added Nicoletta Loggia, chief technical officer of Orchard Therapeutics, in the company press release. "Utilizing our … commercial HSC gene therapy manufacturing platform, we have consistently met the demands for drug product production since the European launch in early 2021. This has enabled us to provide treatment to patients from three continents, including Europe on a commercial basis, the Middle East through treatment abroad programs, and the US, under compassionate use. With the recent US approval, we are excited to further expand access to this vital therapy for eligible children with early-onset MLD."


1. Orchard Therapeutics. Orchard Therapeutics Receives EC Approval for Libmeldy for the Treatment of Early-Onset Metachromatic Leukodystrophy (MLD). Press Release, Dec. 21, 2020.

Source: Food and Drug Administration and AGC Biologics