FDA Approves Gene Therapy for Rare Disease MDL

The FDA has approved Lenmeldy (atidarsagene autotemcel), the first gene therapy to treat children with juvenile metachromatic leukodystrophy (MLD).

Metachromatic leukodystrophy is a rare and life-threatening inherited disease of the body’s metabolic system. It is caused by a mutation in the arylsulfatase-A (ARSA) gene, which results in the accumulation of sulfatides in the brain and other areas of the body. Over time, the nervous system is damaged, leading to neurological problems such as motor, behavioral and cognitive regression, severe spasticity and seizures. Patients with MLD gradually lose the ability to move, talk, swallow, eat and see.

Developed by Orchard Therapeutics, Lenmeldy is one-time gene therapy. Patients’ stem cells are removed and are genetically modified. They are then returned to the patient by intravenous infusion to deliver the corrected version of the gene. It is approved in Europe and the United Kingdom with the brand name Libmeldy for the same indication.

According to the FDA, the safety and effectiveness of Lenmeldy was assessed based on data from 37 children who received Lenmeldy in two single-arm, open-label clinical trials and in an expanded access program. Children who received treatment with Lenmeldy were compared with untreated children.

In children with MLD, treatment with Lenmeldy significantly reduced the risk of severe motor impairment or death compared with untreated children. All children with pre-symptomatic late infantile MLD who were treated with Lenmeldy were alive at 6 years of age, compared with only 58% of children in the natural history group. At 5 years of age, 71% of treated children were able to walk without assistance. Eighty five percent of the children treated had normal language and performance IQ scores, which has not been reported in untreated children.

The most common side effects of Lenmeldy are fever and low white blood cell count, mouth sores, respiratory infections, rash, medical line infections, viral infections, fever, gastrointestinal infections and enlarged liver.

In January, the Japanese company Kyowa Kirin acquired Orchard Therapeutics.