Celebrating the Most Expensive Drug for the Disease You Never Heard Of

When doctors at Children’s Hospital of Philadelphia diagnosed Maria Kefalas’ 2-year-old daughter Cal in 2012 with metachromatic leukodystrophy, an ultra-rare and deadly neurological condition, a social worker gave her paperwork to apply for Medicaid and said, “We’re going to fast-track your Make-A-Wish vacation because you don’t have time.”

“I remember thinking, could I leap out of the window of the ninth floor of CHOP?” Kefalas said of her reaction. “And I believe I threatened to murder several neurologists.”

Metachromatic leukodystrophy (MLD), a lysosomal storage disorder, causes catastrophic damage to the brain and peripheral nervous system. Ninety days after symptom onset, Kefalas said, these kids lose everything. They lose the ability to walk, they need a feeding tube, they become nonverbal if they were even speaking. Life expectancy is about three and a half years after symptom onset. Cal was unusual in that she lived to age 12.

A year after Cal’s diagnosis, Kefalas learned of an experimental gene therapy in development at the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy. It was too late for her daughter. To be eligible for the therapy children needed to be presymptomatic infants. But today, if a child can be diagnosed before symptoms manifest, there is hope. Orchard Therapeutics won U.S. Food and Drug Administration approval for that gene therapy, now known as Lenmeldy, the first gene therapy for the condition. It was previously approved in Europe as Libmeldy.

After her daughter’s diagnosis, Kefalas decided to set up a foundation to raise money to provide funding to families who had children with MLD to pay for palliative care, but once a publication reported results on the experimental MLD gene therapy, a physician at CHOP told her she should take the money she raised to get children to Milan to participate in the study. Since 2013, that is what she did.

She worked with families from Brazil, Australia, and New Zealand to get children treated through the clinical trials. And she’s been on a mission to do what she could to get Lenmeldy approved. As executive director of Cure MLD, an umbrella organization of patient advocacy organizations, she’s helped organize a listening session with the FDA in 2019 and later a Patient Focused Drug meeting with the agency. She’s known in the halls of the National Institutes of Health and the FDA, and jokes that whenever Center for Biologics Evaluation and Research Director Peter Marks sees her, he acknowledges her and heads in the other direction.

When Lenmeldy won approval last week, headlines in major news publications echoed a fact about the therapy. It was hailed as the world’s most expensive drug at $4.25 million. That is true, but belies the fact that a one-team treatment has the potential to allow a child with a disease that will rob them of their abilities before ending their lives, to live without the loss of their cognitive abilities and motor skills. There will be time for debates about pricing and value, but we should first acknowledge the marvel of such a therapy.

For Kefalas knows many people will focus on the eye-popping price tag of the therapy. But she also knows, as she told the United Kingdom’s National Institute for Health and Care Excellence, “an untreated child is going to cost you millions.”

By the time Kefalas’ daughter Cal died, she had 1,747 confirmed contacts with healthcare practitioners in the ten years she lived after her diagnosis.

“An untreated child is going to take out the entire family for you. I gained 70 pounds. My late husband had cancer and he died of multiple myeloma in 2020. His multiple myeloma reemerged while Cal was in the PICU one winter. He was across the street from CHOP and he wouldn’t go to his oncologist because he wouldn’t leave his daughter at the hospital. He said, ‘I could feel the cancer coming back,’” said Kefalas. “My older children have suffered tremendously—mental health issues, trauma, lost childhood. The cost is so immense.”

Kefalas said that there’s an access issue and there’s a pricing issue. She feels, as an advocate, her job is to fight for access.

“Right now, it’s important for me to talk about the transformational power of gene therapy, talk about the challenges and acknowledge the challenges for reimbursement, acknowledge the challenges for access, acknowledge the challenges around pricing,” she said noting there are plenty of opportunities to address cost in the American healthcare system. “The rare disease gene therapy space is not the thing that’s going to bankrupt American healthcare.”