FDA Approves First Gene Therapy for Children with Metachromatic Leukodystrophy

The Food and Drug Administration (FDA) granted approval for Lenmeldy (atidarsagene autotemcel, Orchard Therapeutics, London, UK), the first gene therapy for children with pre-symptomatic late infantile, pre-symptomatic early juvenile, or early symptomatic early juvenile metachromatic leukodystrophy (MLD). MLD is a rare genetic disorder affecting the brain and nervous system caused by a deficiency of the enzyme arylsulfatase A (ARSA), leading to sulfatide accumulation and severe neurological damage. The therapy involves a one-time infusion of genetically modified hematopoietic stem cells (HSCs) containing functional ARSA genes, aiming to halt disease progression.

Lenmeldy's approval was based on data from clinical trials showing improved motor function and survival rates in treated children compared to untreated individuals. Notably, treated children exhibited enhanced motor skills, cognitive function, and survival rates, highlighting the therapy's potential to alter disease outcomes positively.

According to a statement from Nicole Verdun, MD, Director of the Office of Therapeutic Products at the FDA’s Center for Biologics Evaluation and Research (CBER), “MLD is a devastating disease that profoundly affects the quality of life of patients and their families. “This approval represents important progress in the advancement and availability of effective treatments, including gene therapies, for rare diseases.”

Treatment with Lenmeldy requires preconditioning. The safety profile of Lenmeldy includes common side effects like fever and infections, necessitating close monitoring post-treatment for potential complications such as blood clots or encephalitis. Patients are advised to undergo lifelong monitoring for blood-related issues due to a potential risk of blood cancer associated with the therapy.