Lenmeldy Approved for Children With Metachromatic Leukodystrophy

The Food and Drug Administration (FDA) has approved Lenmeldy (atidarsagene autotemcel) for the treatment of children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ) or early symptomatic early juvenile (ESEJ) metachromatic leukodystrophy. 

Metachromatic leukodystrophy (MLD) is a rare inherited lysosomal storage disease caused by a mutation in the arylsulfatase-A (ARSA) gene. This results in a deficiency in the arylsulfatase-A enzyme that leads to a buildup of sulfatides in the brain and other areas of the body. MLD patients lose both motor and cognitive function because of the damage caused by this buildup. Lenmeldy is a one-time, individualized single-dose infusion made from a patient’s own hematopoietic stem cells, which have been genetically modified to include functional copies of the ARSA gene.

The approval was based on data from 37 pediatric patients with MLD treated with Lenmeldy who were enrolled in 2 open-label clinical trials or treated under expanded access frameworks. Study participants were compared with natural history data from 49 untreated patients. 

The composite endpoint was severe motor impairment-free survival, defined as the interval from birth to the first occurrence of loss of locomotion and loss of sitting without support (Gross Motor Function Classification-MLD [GMFC-MLD] Level ≥ 5) or death.

Finding showed treatment with Lenmeldy significantly extended severe motor impairment-free survival in children with PSLI MLD compared with untreated natural history children. At 5 years old, 100% of PSLI children treated with Lenmeldy remained event-free compared with none of the children in the natural history cohort. Additionally, 12 of the 17 children who were at least 5 years old at last follow-up retained independent ambulation (GMFC-MLD level ≤ 1).

Treatment with Lenmeldy significantly extended overall survival compared with untreated natural history. At 6 years from birth, all 14 PSLI MLD children with sufficient follow-up who received Lenmeldy were alive. At this timepoint, 42% (n=10) of children in the natural history cohort had died. As for cognitive function, 85% of the PSLI MLD children treated with Lenmeldy had normal language and performance IQ scores, which contrasted with natural history children who demonstrated severe cognitive impairment early in their disease course. 

Lenmeldy was also associated with preservation of motor function and cognitive skills in children with PSEJ and ESEJ MLD.

The most common adverse reactions reported with Lenmeldy were febrile neutropenia, stomatitis, elevated D-dimer, respiratory tract infections, rash, device related infections, other viral infections, neutropenia, elevated liver enzymes, pyrexia, gastroenteritis, and hepatomegaly. 

The prescribing information also includes warnings and precautions related to thrombosis and thromboembolic events, encephalitis, serious infection, veno-occlusive disease, delayed platelet engraftment, risk of neutrophil engraftment failure, risk of insertional oncogenesis, and risk of hypersensitivity reactions.

Lenmeldy is supplied as a single-dose cell suspension for intravenous infusion. Hematopoietic stem cell mobilization, apheresis, and myeloablative conditioning are required prior to Lenmeldy infusion. The minimum and maximum recommended dose of Lenmeldy is based on MLD disease subtype.

“The FDA approval of Lenmeldy opens up tremendous new possibilities for children in the US with early-onset MLD who previously had no treatment options beyond supportive and end-of-life care,” said Bobby Gaspar, MD, PhD, co-founder and chief executive officer of Orchard Therapeutics.

The Company is expected to provide details about the product launch later this week.

This article originally appeared on MPR