FDA Gives Green Light to First Gene Therapy for Pediatric MLD
Lenmeldy from Orchard Therapeutics has become the inaugural gene therapy to receive approval in the United States for the treatment of metachromatic leukodystrophy in children.
Orchard Therapeutics received FDA approval on March 18, 2024 for Lenmeldy (atidarsagene autotemcel), making it the first gene therapy approved by the FDA to treat children with pre-symptomatic late infantile, pre-symptomatic early juvenile, or early symptomatic early juvenile metachromatic leukodystrophy (MLD) in the United States. After receiving approval, AGC Biologics has announced that it will produce the therapy at its Milan, Italy, facility.
As per a press release from the FDA, MLD is a genetic disease that is both rare and debilitating. It impacts the brain and nervous system due to a deficiency of the arylsulfatase A (ARSA) enzyme. This lack results in an accumulation of sulfatides within the cells, resulting in harm to both the central and peripheral nervous systems. This ultimately leads to a decline in motor and cognitive abilities and premature mortality. MLD has a prevalence of approximately one in every 40,000 individuals in the US, and unfortunately, there is currently no known cure for this condition. At present, the main approach is to provide support and address the symptoms.
Lenmeldy is a unique treatment that involves infusing the patient with their own hematopoietic stem cells. This one-time procedure is tailored to each individual and administered in a single dose. The patient's HSCs are collected and modified to include functional copies of the ARSA gene, making the process straightforward and easy to understand. The modified cells are then transplanted back into the patient, where they integrate into the bone marrow and provide the body with myeloid cells that produce the ARSA enzyme. An enzyme is utilized to break down the accumulation of sulfatides, potentially halting the advancement of MLD.
Before starting Lenmeldy treatment, patients are required to undergo high-dose chemotherapy. This process eliminates cells from the bone marrow, which can later be replaced with the modified HSCs, as stated in the FDA release.
Lenmeldy's application received expedited review and multiple designations, highlighting its importance in treating rare pediatric diseases and advancing regenerative medicine.
Approval for production
After receiving approval from Lenmeldy, AGC Biologics, a contract development and manufacturing organization (CDMO), has announced that its Milan, Italy, site has obtained clearances from both US and European regulators. This means that the site can now utilize approved commercial processes to provide patients with the gene therapy. The company is set to commence commercial manufacturing for the lentiviral vector and genetically modified cell drug product (DP) for Lenmeldy at the site.
As per the company's press release, the Milan site has achieved a significant milestone by being the sole CDMO site to obtain FDA clearance for the commercial production of this gene therapy specifically for patients in the US. According to AGC Biologics, the FDA approval marks the successful completion of their partnership with Orchard Therapeutics, which began in 2018. This collaboration also involved navigating the product's commercial approval by the European Commission in 2021, where it is known as Libmeldy. AGC Biologics' Milan site has a special connection to the entire lifecycle of this product. Our facility and scientific teams have collaborated with various companies over the past two decades to support the development and commercialization of this treatment.
Source: FDA; AGC Biologics; Orchard Therapeutics
