NEW YORK – The US Food and Drug Administration on Monday approved Orchard Therapeutics' Lenmeldy (atidarsagene autotemcel) as the first gene therapy for children with metachromatic leukodystrophy (MLD).
MLD is a rare genetic disease, in which deficiency of the enzyme arylsulfatase A (ARSA) leads to a buildup of sulfatides in cells. This accumulation of sulfatides damages the brain and nervous system causing patients to lose motor and cognitive functions.
The agency approved the treatment specifically for patients with the presymptomatic late infantile, presymptomatic early juvenile, or early symptomatic, early juvenile stages of the disease.
"This is the first FDA-approved treatment option for children who have this rare genetic disease," Peter Marks, director of the FDA's Center for Biologics Evaluation and Research, said in a statement. "We remain committed to advancing scientific and regulatory principles that enable the efficient development and review of safe, effective, and innovative products that have the potential to change patients' lives."
Orchard Therapeutics, which has been acquired by Kyowa Kirin, developed Lenmeldy as a one-time infusion comprising a patient's own hematopoietic stem cells, which have been genetically modified ex vivo to include functional copies of the ARSA gene. Before receiving the gene therapy, patients must undergo high-dose chemotherapy to remove cells from the bone marrow, which are replaced with the modified cells.
The FDA approved Lenmeldy based on data from 37 children with MLD who received the gene therapy in two single-arm, open-label clinical trials and through an expanded access program. The data showed that Lenmeldy significantly reduced the risk of severe motor impairment or death compared to untreated children from a natural history study. All Lenmeldy-treated children with presymptomatic late infantile MLD were alive at 6 years old compared to only 58 percent of children in the natural history group. Among children with presymptomatic early juvenile and early symptomatic, early juvenile MLD, there was also evidence of slowing motor or cognitive disease with Lenmeldy treatment.
The most common side effects were fever and low white blood cell count, mouth sores, respiratory infections, rash, medical line infections, viral infections, fever, gastrointestinal infections, and enlarged liver. The FDA said that patients should be monitored for neutrophil counts and risk of delayed platelet engraftment after infusion until engraftment has been achieved. The FDA also cautioned that treatment with Lenmeldy may be associated with formation of blood clots or encephalitis and may carry a potential risk of blood cancer.
Patients who receive the gene therapy should be monitored lifelong for hematologic malignancies and have a complete blood count annually as well as an integration site analysis for at least 15 years after treatment, according to the FDA.
The gene therapy has already been approved by the European Commission, UK Medicines and Healthcare Products Regulatory Agency, and Swiss Agency for Therapeutic Products. In Europe, the product is branded as Libmeldy.