A wonder drug called Lenmeldy has finally been approved by the US Food and Drug Administration. This drug treats a debilitating and lethal disease that mostly affects infants called metachromatic leukodystrophy (MLD). Children affected by this very rare genetic disease that affects the brain and nervous system lose their ability to move, talk, and even think. The patients succumb to a vegetative state, withering and ultimately dying before age 5.

Clinical trials have shown that Lenmeldy helped the children recover. These children now lead normal lives, walking on their own and going to school. Their IQ tests are on par with their peers. Some have been on this treatment for more than 12 years and show no sign of deterioration.

Now with the FDA’s official stamp of approval, all children with MLD can access this treatment. Well, theoretically, that is. Lenmeldy (atidarsagene autotemcel) is officially the world’s most expensive drug. On the day they received approval, the company behind the drug set the price at a staggering $4.25 million. According to Ars Technica, that’s hundreds of thousands of dollars more expensive than experts from the nonprofit Institute for Clinical and Economic Review had previously anticipated to be the maximum fair price. The institute’s anticipated range was $2.29 million to just under $4 million.

MLD: a very and devastating disease

MLD is a rare genetic disorder that leads to the buildup of sulfatides, a type of fat, in the body. This buildup damages the myelin sheath, the protective fatty layer that surrounds nerves in both the central and peripheral nervous systems. The disease manifests in three forms, categorized by the age at which symptoms first appear: late-infantile MLD, juvenile MLD, and adult MLD.

Despite differences in timing, all types of MLD impair intellectual and motor function, with symptoms that may include speech difficulties, seizures, trouble walking, and changes in personality and behavior. Mutations in the ARSA gene primarily cause MLD, though in rare cases, the PSAP gene is also implicated.

The term “metachromatic leukodystrophy” derives from the observation that, under a microscope, the accumulated sulfatides in cells stain differently than other cellular materials, appearing as color-changing granules.

“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, the director of the Office of Therapeutic Products at FDA’s Center for Biologics Evaluation and Research (CBER).

An game-changing treatment

Lenmeldy, developed by Orchard Therapeutics, counteracts the damage caused by metachromatic leukodystrophy (MLD) by introducing a functional ARSA gene into the body. Through a single infusion, patients receive their own stem cells now genetically modified to carry a working ARSA gene.

To make room for these engineered cells, patients first undergo chemotherapy to eliminate their existing stem cells from the bone marrow. Once in place, these genetically modified stem cells begin to produce myeloid cells. These cells circulate throughout the body via the blood, creating ARSA enzymes that can stop the progression of MLD.

Lenmeldy has been available in Europe since 2020, but it took four more years to bring it to the US.

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

According to the results of the Lenmeldy trial:

• All children with pre-symptomatic late infantile MLD treated with Lenmeldy were alive at 6 years, versus only 58% in the untreated group.
• At 5 years, 71% of those treated could walk unassisted.
• Eighty-five percent of treated children had normal language and performance IQ scores, unlike any untreated child.
• Children with pre-symptomatic early juvenile and symptomatic early juvenile MLD experienced a slowdown in motor and cognitive disease progression when treated.
• Common side effects of Lenmeldy include:
  • Fever
  • Low white blood cell count
  • Mouth sores
  • Respiratory infections
  • Rash
  • Infections related to medical lines
  • Viral infections
  • Gastrointestinal infections
  • Enlarged liver

Orphan drugs and ridiculous prices

The condition affects one in 40,000 babies in the US. This technically makes Lenmeldy a so-called “orphan drug”, because it’s specifically developed to treat, prevent, or diagnose a rare disease. Drug discovery is extremely expensive. R&D expenses for orphan drugs must be recouped from a small number of patients, resulting in high drug treatment costs per patient.

This explains why Lenmeldy is so expensive. However, even for an orphan drug, the ridiculously high price tag is suspicious, exceeding any previous sensible estimates. This raises serious questions about access to this drug, whose cost is unlikely to be affordably supported health insurance plans. The treatment needs to be taken as early as possible, otherwise it’s no longer effective.

“Unless states have allocated appropriately for it, and looked at the drug pipeline, they may not be prepared for what could be significant cost spikes,” Edwin Park, a research professor at the McCourt School of Public Health at Georgetown University, told CNN.

Lenmeldy’s eye-watering price isn’t unheard of. Another gene therapy called Hemgenix, approved in 2022 to treat a blood clotting disorder called hemophilia B, had a list price of $3.5 million for a one-time treatment. Elvevidys, which was approved in 2023 for muscular dystrophy, costs $3.2 million. And Skysona, approved in 2022 for a disease related to MLD called adrenoleukodystrophy, costs $3 million for a one-time dose.