The U.S. Food and Drug Administration (FDA) has approved Lenmeldy (atidarsagene autotemcel) for the treatment of children with metachromatic leukodystrophy (MLD). The treatment is the first gene therapy to be approved by the FDA for children with this indication.
MLD is a genetic condition caused by changes in the ARSA and PSAP genes. It is characterized by the accumulation of sulfatides in cells, especially of the nervous system. The accumulation results in progressive deterioration of white matter in the brain, leading to loss of intellectual functions and motor skills. Other symptoms may include:
- Loss of sensation in extremities
- Incontinence
- Seizures
- Paralysis
- Inability to speak
- Blindness
- Hearing loss
Treatment of MLD has traditionally focused on symptom management. Atidarsagene is a one-time, individualized, single-dose infusion derived from the patient’s own hematopoietic stem cells (HSCs). The HSCs are genetically modified to include functional copies of the ARSA gene.
These modified stem cells are then reintroduced into the patient, where they engraft within the bone marrow. The engrafted cells then produce the ARSA enzyme, which aids in breaking down the harmful sulfatides, potentially halting the progression of MLD.
Before the treatment, patients must undergo high-dose chemotherapy to remove cells from the bone marrow, making way for the gene therapy.
The effectiveness of atidarsagene was assessed based on data from 37 children who received the treatment in two single-arm, open-label clinical trials and an expanded access program. The results showed that MLD patients treated with atidarsagene significantly lowered the risk of severe motor impairment or death compared to untreated children.
The most common adverse events with this treatment include fever, low white blood cell count, mouth sores, respiratory infections, and rash.
The price for one-time gene therapy is $4.25 million, making it one of the most expensive drugs in the world. Orchard Therapeutics’ press release provides more information.
Previously, CheckRare talked with Paul Orchard, MD of the University of Minnesota Medical School about this disease and the gene therapy. That interview is below.
For more information on MLD and other rare genetic conditions, visit https://checkrare.com/diseases/congenital-and-genetic-conditions/
