FDA OKs Gene Therapy for Rare Neural Disorder

The U.S. Food and Drug Administration authorized Lenmeldy, the first gene therapy for treating children with metachromatic leukodystrophy. At a price tag of $4.25 million, it is now the most expensive drug in the United States.

About one in 40,000 Americans have metachromatic leukodystrophy (MLD), a rare genetic disease affecting the brain and nervous system, which manifests in the loss of motor and cognitive function and early death.

Currently, there is no cure for the condition, with treatment typically focusing on symptom management and supportive care.

Lenmeldy (atidarsagene autotemcel), the first gene therapy for the disease, is approved in pediatric patients with pre-symptomatic late infantile, pre-symptomatic early juvenile or early symptomatic early juvenile metachromatic leukodystrophy (MLD).

Today marked a historic day for the MLD community as the FDA has officially approved MLD gene therapy treatment, Lenmeldy. On this monumental day, listen to The Calliope Joy Foundation co-founder Maria Kefalas share why this is a historic development for the MLD community. pic.twitter.com/LoDsDjlg8u

undefined The Calliope Joy Foundation (@caljoyfndtion) March 18, 2024

"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," Peter Marks, M.D., Ph.D., director of the FDA's Center for Biologics Evaluation and Research (CBER), said in a statement.

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

MLD is caused by the deficiency of an ARSA enzyme, which leads to a buildup of sulfatides (fatty substances) in the cells. This buildup damages the central and peripheral nervous system.

The modified stem cells are transplanted back into the patient, where they attach and multiply within the bone marrow. They supply the body with myeloid (immune) cells that produce the ARSA enzyme, which helps break down the buildup of harmful sulfatides and may stop the disease progression.

Before treatment with Lenmeldy, patients must undergo high-dose chemotherapy to remove cells from the bone marrow.

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

Treatment with Lenmeldy significantly reduced the risk of severe motor impairment or death compared with untreated children with MLD.

All children with pre-symptomatic late infantile MLD who were treated with Lenmeldy were alive at 6 years of age, compared to only 58% of children who did not receive the treatment.

At the age of five, 71% of children treated with Lenmeldy were able to walk without assistance. The majority (85%) of the children who received the therapy had normal language and performance IQ scores, which has not been reported in untreated children.

Fever, low white blood cell count, and respiratory and gastrointestinal infections were among the most common side effects of the therapy.

The most expensive drug in the US

Lenmeldy's manufacturer, Orchard Therapeutics, said the drug's wholesale acquisition cost is $4.25 million.

Before its approval, the Institute for Clinical and Economic Review concluded that the price range between $2.3M to $3.9M matches the clinical benefits patients are expected to receive.

In 2020, atidarsagene autotemcel was approved in Europe under the brand name Libmeldy for 2.9 million euros ($3.16 million).

The Calliope Joy Foundation, which supports metachromatic leukodystrophy patients, called the approval a historic development for the MLD community.