Advice

following a full submission assessed under the ultra-orphan process:

Treatment of metachromatic leukodystrophy (MLD) characterized by biallelic mutations in the arylsulfatase A (ARSA) gene leading to a reduction of the ARSA enzymatic activity:

  • in children with late infantile or early juvenile forms, without clinical manifestations of the disease,

  • in children with the early juvenile form, with early clinical manifestations of the disease, who still have the ability to walk independently and before the onset of cognitive decline.

Key points:

  • MLD is a condition that affects the nervous system resulting in multiple incapacitating symptoms including loss of motor and cognitive functions and early death, especially in patients with early disease onset. The caring burden impacts on the whole family.

  • In combined data from a phase I/II study and three expanded access programs, atidarsagene autotemcel increased gross motor function scores in pre-symptomatic late infantile and in pre- and early symptomatic early juvenile MLD patients, when compared with a natural history cohort of MLD patients. Survival data in late infantile patients treated with atidarsagene autotemcel are encouraging.

  • Quality of life outcomes were not directly assessed in the studies.

  • The sample size and follow-up were limited. Maintenance of effects and long-term safety are uncertain. In early symptomatic patients, treatment effect was less evident and more varied than in the pre symptomatic patients.

Despite a Patient Access Scheme (PAS), the treatment’s cost in relation to its health benefits remains high.

Medicine details

Medicine name:
atidarsagene autotemcel (Libmeldy)
SMC ID:
SMC2413
Indication:

For treatment of metachromatic leukodystrophy (MLD) characterized by biallelic mutations in the arysulfatase A (ARSA) gene leading to a reduction of the ARSA enzymatic activity:

  • in children with late infantile or early juvenile forms, without clinical manifestations of the disease

  • in children with the early juvenile form, with early clinical manifestations of the disease, who still have the ability to walk independently and before the onset of cognitive decline
Pharmaceutical company
Orchard Therapeutics
BNF chapter
Nutrition and blood
Submission type
Ultra-orphan initial assessment
Date advice published
11 April 2022