Lenmeldy Approved to Treat Metachromatic Leukodystrophy

Orchard Therapeutics received approval from the U.S. Food and Drug Administration (FDA) on March 18, 2024, for Lenmeldy^™ (atidarsagene autotemcel). A stem cell-based gene therapy, Lenmeldy is indicated to treat children who have early-onset metachromatic leukodystrophy (MLD), which includes some forms of the condition that are not yet symptomatic. Lenmeldy will be given as one intravenous (IV) infusion of the patient’s stem cells, which have been collected and altered to contain working copies of a gene to produce a missing enzyme. Doses depend on the child’s weight and the type of MLD being treated. Launch and pricing plans will be announced later this week. Complete prescribing information for Lenmeldy is here.

At a Glance

• Brand (Generic) Name: Lenmeldy (atidarsagene autotemcel)
• Manufacturer: Orchard Therapeutics
• Date Approved: March 18, 2024
• Indication: to treat pre-symptomatic late infantile, pre-symptomatic early juvenile, and early symptomatic early juvenile MLD
• Dosage Forms Available: A single-dose cell suspension containing 2 to 11.8× 10⁶ cells/mL (1.8 to 11.8 x 10⁶ CD34⁺ cells/mL)
• Launch Date: to be announced later this week
• Estimated Cost: to be announced later this week
• An inherited disease, MLD results from mutations in the arylsulfatase-A (ARSA) gene, which is responsible for making the enzyme, arylsulfatase. Lack of the enzyme causes the abnormal accumulation of lipids called sulfatides, which destroy protective myelin coatings in the brain and nerves.
• The MLD Foundation estimates that roughly 2,450 patients in the U.S. have the condition, but its true prevalence is uncertain.
• MLD’s early-onset forms include late infantile, which typically is diagnosed by the age of four years old, and early juvenile, usually diagnosed between four years and six years of age.
• By their third birthdays, symptoms, such as problems with walking, are apparent for about one-half of patients who have MLD. The children’s conditions deteriorate – often over only a few months – and, eventually, they cannot eat, move, see, or speak. Life expectancy is only around two years to five years after symptoms appear.
• Lenmeldy replaces the mutated gene so that an active ARSA enzyme is produced.
• The child will be hospitalized for collection of stem cells and then again for pre-treatment with busulfan to suppress bone marrow activity before infusion of Lenmeldy. It must be given by trained healthcare providers in specially equipped medical centers.
• In a clinical trial, 37 patients who were treated with Lenmeldy for early-onset MLD have been able to function physically and mentally for as long as 12 years.
• More than 50% of study patients treated with Lenmeldy developed febrile neutropenia, stomatitis, and/or respiratory tract infections.
• Current treatment for MLD centers on relieving symptoms. No other drug is indicated to treat the underlying cause.
• Approved under the FDA’s Priority Review process, Lenmeldy has Orphan Drug, Rare Pediatric Disease, and Regenerative Medicine Advanced Therapy status.