The US Food and Drug Administration (FDA) has approved the first gene therapy for metachromatic leukodystrophy (MLD), a rare and debilitating genetic disease affecting the brain and nervous system.
Atidarsagene autotemcel (Lenmeldy) was granted priority review and had orphan drug, rare pediatric disease, and regenerative medicine advanced therapy designations.
The approved indication is for presymptomatic late infantile, presymptomatic early juvenile, or early symptomatic early juvenile MLD.
“MLD is a devastating disease that profoundly affects the quality of life of patients and their families. This approval represents important progress in the advancement and availability of effective treatments, including gene therapies, for rare diseases,” Nicole Verdun, MD, director of the Office of Therapeutic Products in the Center for Biologics Evaluation and Research, said in a statement.
MLD affects an estimated 1 in every 40,000 individuals in the United States. There is no cure. Treatment typically focuses on supportive care and symptom management.
MLD is caused by a deficiency of arylsulfatase A (ARSA), leading to a buildup of sulfatides in cells, which causes damage to the central and peripheral nervous system, leading to loss of motor and cognitive function and early death.
Lenmeldy is a one-time, individualized single-dose infusion made from the patient’s hematopoietic stem cells, which have been genetically modified to include functional copies of the ARSA gene.
The safety and effectiveness of Lenmeldy were evaluated on the basis of data from 37 children with MLD who received Lenmeldy in two single-arm, open-label clinical trials and in an expanded access program.
In children with MLD, treatment with Lenmeldy significantly reduced the risk for severe motor impairment or death (the primary outcome) compared with untreated children (natural history group).
All children with presymptomatic 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 and 85% had normal language and performance IQ scores, which has not been reported in untreated children.
In addition, children with presymptomatic early juvenile and early symptomatic early juvenile MLD showed slowing of motor and cognitive disease.
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.
“After infusion with Lenmeldy, patients should be monitored for neutrophil counts and risk of delayed platelet engraftment until engraftment has been achieved,” the FDA says.
Treatment with Lenmeldy may be associated with formation of blood clots or encephalitis and carries a risk for blood cancer. Patients receiving Lenmeldy require continuous monitoring for hematologic malignancies; this monitoring should include a complete blood cell count with differential annually and integration site analysis, as warranted, for at least 15 years after treatment, the FDA says.
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