FDA approves Lenmeldy for early juvenile metachromatic leukodystrophy

Key takeaways:

• Metachromatic leukodystrophy is an incurable rare genetic disease.
• At 5 years of age, 71% of children given Lenmeldy were able to walk without assistance, and 85% had normal language scores.

The FDA has approved Lenmeldy as the first gene therapy to treat children with pre-symptomatic late infantile, pre-symptomatic early juvenile or early symptomatic early juvenile metachromatic leukodystrophy.

Approval for Lenmeldy (atidarsagene autotemcel) was granted to Orchard Therapeutics, according to a press release from the FDA.

The FDA had previously granted Lenmeldy priority review, orphan drug, rare pediatric disease and regenerative medicine advanced therapy designations.

Metachromatic leukodystrophy is an incurable genetic disease that affects the brain and nervous system. It is caused by a deficiency of an enzyme called arylsulfatase A (ARSA), which leads to a buildup of sulfatides in the cells. This buildup damages the central and peripheral nervous system, presenting in patients with loss of motor and cognitive function and early death.

The condition is estimated to affect one in every 40,000 individuals in the United States, according to the release.

Lenmeldy is a one-time, individualized single-dose infusion created from the patient’s own hematopoietic (blood) stem cells, which have been genetically modified to include functional copies of the ARSA gene. The stem cells are collected from the patient and modified by adding a functional copy of the ARSA gene, then transplanted back into the patient where they engraft inside bone marrow.

Prior to treatment, patients must undergo high-dose chemotherapy to remove cells from bone marrow that are replaced with the modified cells in Lenmeldy.

Safety and efficacy was determined by data from 37 children who received the novel gene therapy in two single-arm, open-label clinical trials and in an expanded access program. In children with MLD, treatment with Lenmeldy significantly reduced the risk of severe motor impairment or death compared with children who were not treated.

According to data cited in the release, at 5 years of age, 71% of children given Lenmeldy were able to walk without assistance, and 85% had normal language and performance IQ scores, which was not observed in children who have not undergone treatment. Children with pre-symptomatic early juvenile and early symptomatic early juvenile MLD additionally had slowing of motor and/or cognitive disease.

“This is the first FDA-approved treatment option for children who have this rare genetic disease,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in the 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.”