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FDA green lights first-ever therapy for rare genetic disease in kids

The US Food and Drug Administration has cleared Orchard Therapeutics’s gene therapy to treat a disease affecting the brain and nervous system in children — the regulator’s first ever for the disorder.

HQ Team

March 19, 2023: The US Food and Drug Administration has cleared Orchard Therapeutics’s gene therapy to treat a disease affecting the brain and nervous system in children — the regulator’s first ever for the disorder.

The FDA gave the green light to Lenmeldy, gene therapy for the treatment of children with pre-symptomatic late infantile, pre-symptomatic early juvenile or early symptomatic early juvenile metachromatic leukodystrophy (MLD).

The safety and effectiveness of the therapy were assessed and based on data from 37 children who received Lenmeldy in clinical trials and an expanded access program.

The primary efficacy endpoint was severe motor impairment-free survival, defined as the interval from birth to the first occurrence of loss of locomotion and loss of sitting without support or death. 

In children with MLD, treatment with Lenmeldy significantly reduced the risk of severe motor impairment or death compared with untreated children, according to an FDA statement.

Walk without assistance

All children with pre-symptomatic late infantile MLD who were treated with Lenmeldy were alive at six years of age, compared to only 58% of children in the natural history group or untreated.

At five years of age, 71% of treated children were able to walk without assistance.

Eighty-five per cent of the children treated had normal language and performance IQ scores, which has not been reported in untreated children. 

In addition, children with pre-symptomatic early juvenile and early symptomatic early juvenile MLD showed slowing of motor and cognitive disease.

Metachromatic leukodystrophy is a debilitating, rare genetic disease affecting the brain and nervous system.

Enzyme deficiency

It is caused by a deficiency of an enzyme called arylsulfatase, leading to a buildup of fatty substances in the cells. 

The buildup causes damage to the central and peripheral nervous system, manifesting in loss of motor and cognitive function and early death.

An estimated one in every 40,000 individuals in the US have MLD. There is no cure for MLD, and treatment typically focuses on supportive care and symptom management.

“This is the first FDA-approved treatment option for children who have this rare genetic disease,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research (CBER).

Lenmeldy is a one-time, individualized single-dose infusion made from the patient’s blood stem cells, which have been genetically modified to include functional copies of the arylsulfatase gene. 

Multiply within bone marrow

The stem cells are collected from the patient and modified by adding a functional copy of the arylsulfatase gene. 

The modified stem cells are transplanted back into the patient where they attach and multiply within the bone marrow. 

The modified stem cells supply the body with immune cells that produce the arylsulfatase enzyme, which helps break down the harmful build-up of sulfatides and may stop the progression of MLD.

Before the treatment patients have to undergo high-dose chemotherapy, a process that removes cells from the bone marrow so they can be replaced with the modified cells in Lenmeldy.

Potential risk

The regulator pointed out the potential risk of blood cancer associated with the treatment, and the formation of blood clots or a type of swelling of brain tissues.

“MLD is a devastating disease that profoundly affects the quality of life of patients and their families. Advancements in treatment options offer hope for improved outcomes and the potential to positively influence the trajectory of disease progression,” said Nicole Verdun, MD, director of the Office of Therapeutic Products in CBER.

“This approval represents important progress in the advancement and availability of effective treatments, including gene therapies, for rare diseases.”

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