A lifesaving therapy for children with a rare disease is now the world’s most expensive drug, raising questions about access

Announced on Wednesday, a groundbreaking gene therapy for the fatal genetic disorder metachromatic leukodystrophy (MLD) will come with a staggering wholesale price tag of $4.25 million, making it the most expensive medicine globally.

Lenmeldy, the first-ever therapy for this rare and devastating disease, received approval from the US Food and Drug Administration just days prior. Typically claiming the lives of affected children before the age of 7, MLD affects around 40 children annually in the US.

While patients rarely directly bear the wholesale cost, it’s a significant consideration for public and private health insurance plans, including state Medicaid plans which cover approximately 4 out of every 10 children in the nation.

Manufacturers of gene therapies defend the hefty prices, emphasizing the substantial benefits they offer – the potential to alleviate or even eradicate a debilitating or fatal illness. They argue that these prices are necessary to cover the substantial expenses incurred during development, testing, and manufacturing.

However, health policy experts warn that the proliferation of gene and cell therapies with exorbitant prices could strain insurers’ capacity to cover them, potentially leading to restrictions in patient access if these therapies are excluded from coverage.

Dr. Bobby Gaspar, CEO of Orchard Therapeutics, the company behind Lenmeldy, lauded the treatment as “paradigm-shifting medicine” with the potential to halt or slow the progression of MLD with a single treatment. Gaspar affirmed the commitment to ensuring broad and sustainable access to eligible patients in the US.

Lenmeldy operates by extracting stem cells from MLD patients and using a harmless virus to introduce functional copies of a defective gene. These repaired cells are then reintroduced into the patient, where they begin producing the lacking enzyme. This process offers long-term benefits, with early patients showing enduring effects even after 12 years.

MLD, an inherited disorder, causes a deficiency of an enzyme crucial for breaking down fatty substances. Without this enzyme, fatty materials accumulate and become toxic to nerves, resulting in progressive loss of movement and cognitive abilities.

For families like Kendra Riley’s from Phoenix, who have been affected by MLD, the FDA’s approval of Lenmeldy brings both hope and heartache. While Riley’s 5-year-old daughter, Olivia, is in hospice care after being diagnosed too late for treatment, her younger daughter, Keira, received the therapy before symptoms appeared and is thriving.

Keira was among the early recipients of the therapy, having received it in Italy in 2020 before it was available in the US. Despite the substantial costs and challenges faced by the family, the therapy has proven immensely beneficial, offering Keira a chance at a normal life free from MLD symptoms.

‘Exciting’ drug development

The Institute for Clinical and Economic Review (ICER), a Boston-based nonprofit that assesses the cost-effectiveness of new medications, released its conclusive evaluation of Lenmeldy last autumn. It projected that the therapy’s cost would align with its anticipated benefits to patients if priced between $2.3 million and $3.9 million. Experts concurred that despite the substantial price tag, the therapy’s outcomes justified its cost. Typically, untreated children with the disease face a life expectancy of merely five years post-diagnosis, whereas the longest-treated patient has now surpassed 12 years and shows signs of normal development.

Dr. David Rind, ICER’s chief medical officer, emphasized the transformative impact of Lenmeldy, stating, “It’s taking a child who would have had a miserable short life and likely giving them a normal life. And that’s worth a lot of money.” Nevertheless, Rind expressed concern over Lenmeldy’s pricing, which exceeded even his expectations.

ICER’s suggested price range of $2.29 million to $3.94 million isn’t indicative of the ideal price, according to Rind, cautioning against manufacturers viewing the upper limit as justified. He highlighted the significant difference of going $310,000 beyond the upper range.

Lenmeldy’s pricing places it among the highest-priced treatments per patient, with precedents like Hemgenix for hemophilia B at $3.5 million and Elvevidys for muscular dystrophy at $3.2 million. However, despite its high cost, Lenmeldy might not yield blockbuster revenues due to the rarity of the disease it targets. Concerns linger over the financial burden on states, particularly in Medicaid coverage, where limited competition may hinder price negotiation.

Edwin Park, a research professor at Georgetown University’s McCourt School of Public Health, stressed the importance of state preparation for potential cost spikes associated with expensive treatments like Lenmeldy. He pointed to the lessons learned from unexpected expenses tied to antiviral drugs for hepatitis C and urged states to allocate resources wisely and closely monitor the drug pipeline to mitigate financial shocks.

New possibilities for patients

Amid the FDA’s efforts to address a backlog of cell and gene therapies accumulated during the pandemic, Lenmeldy’s recent approval marks a significant milestone. The agency has augmented its workforce and established the Office of Therapeutic Products to expedite the review and regulation of these innovative treatments.

While Lenmeldy has been accessible in Europe since 2020, its arrival in the US has been awaited for four additional years. Dr. Nicole Verdun, tasked with spearheading the FDA’s new initiative, sees Lenmeldy’s approval as a positive step forward. She emphasized its significance in advancing effective treatments, including gene therapies, for rare diseases like MLD.

Dr. Barbara Burton, an attending physician specializing in genetics, genomics, and metabolism at the Ann & Robert H. Lurie Children’s Hospital of Chicago, hailed the approval as a pivotal moment for medical professionals. She expressed relief that future generations might be spared the anguish of watching their loved ones suffer from untreated diseases like MLD.

The approval of Lenmeldy has spurred efforts to enhance early detection methods for MLD. Orchard Therapeutics is actively supporting studies on newborn screening tests to identify and treat the condition at its onset. Gaspar from Orchard Therapeutics highlighted progress in newborn screening initiatives, with over 250,000 babies screened and several cases of MLD detected and treated.

Despite the stability of 5-year-old Olivia, who suffers from MLD, her caregiver Riley lives in constant fear of potential infections that could endanger her life. Olivia requires constant care due to her inability to walk or talk, relying on tube feeding. Riley emphasized the importance of therapies to stimulate Olivia’s mind and expressed hope that Lenmeldy’s approval will spare other families from experiencing similar losses.

Reflecting on Olivia’s role as her sister Keira’s guardian angel, Riley emphasized the profound purpose of her life while advocating for better treatments to prevent future tragedies for families affected by MLD.