FDA Approves First Gene Therapy for Children With Metachromatic Leukodystrophy

The Food and Drug Administration on Monday approved the first and only gene therapy for the treatment of children with metachromatic leukodystrophy (MLD), a rare, debilitating, genetic disease that affects the brain and nervous system.

In children with MLD, a deficiency of arylsulfatase A leads to a buildup of sulfatides in the cells. This buildup causes damage to the central and peripheral nervous system, resulting in the loss of motor and cognitive function and early death. There is no cure for MLD, and treatment typically focuses on supportive care and symptom management.

Atidarsagene autotemcel (marketed as Lenmeldy, Orchard Therapeutics) is a one-time, individualized single-dose infusion made from autologous hematopoietic stem cells that have been genetically modified to include functional copies of the ARSA gene using a lentiviral vector.  

FDA based its approval on data from 37 children who received atidarsagene autotemcel in two single-arm clinical trials and an expanded access program. Results showed significant reductions in severe motor impairment or death compared to untreated children. All pre-symptomatic late infantile MLD patients treated with atidarsagene autotemcel were alive at age 6, compared with 58% survival in the untreated group. By age 5, 71% of treated children could walk unassisted, with 85% demonstrating normal language and performance IQ scores. Treatment also slowed disease progression in early juvenile MLD cases.

FDA recommended monitoring patients for neutrophil counts, delayed platelet engraftment and potential risks such as blood clots and encephalitis. Although a risk of blood cancer exists, no cases have been observed thus far in treated patients. In addition, FDA advised lifelong monitoring of treated patients for hematologic malignancies, including annual complete blood counts and integration site analysis for at least 15 years post-treatment.

The application received Priority Review, Orphan Drug, Rare Pediatric Disease and Regenerative Medicine Advanced Therapy (RMAT) designations.