A lifesaving therapy for children with a rare disease

A new gene therapy for the fatal genetic disorder metachromatic leukodystrophy, or MLD, will carry a wholesale price of $4.25 million, its manufacturer announced Wednesday, making it the world's most expensive medicine.

Lenmeldy was approved by the US Food and Drug Administration on Monday and is the first therapy for the rare and devastating disease, which typically kills affected children before they turn 7. About 40 children are born with MLD in the US each year.

The wholesale cost isn't usually what patients pay, but it's a cost that's considered and shouldered by public and private health insurance plans, including state Medicaid plans, which cover roughly 4 out of every 10 children in the United States.

Manufacturers of gene therapies say the big prices reflect big benefits — the chance to be free of a disabling or even fatal disease — and they point out that they need to be able to recoup the steep costs of development, testing, and manufacturing their products.

Health policy experts say that as the list of gene and cell therapies with eye-popping prices grows, it may strain the ability of states and other insurers to cover their costs, and ultimately limit patient access if plans begin to exclude these therapies as a class from coverage.

Dr. Bobby Gaspar, the co-founder and CEO of Orchard Therapeutics, the company that makes Lenmeldy, said the treatment is 'paradigm-shifting medicine and has the potential to stop or slow the progression of this devastating childhood disease with a single treatment.'

'We are committed to enabling broad, expedient, and sustainable access to this important therapy for eligible patients with early-onset MLD in the U.S.,' Gaspar said in a statement.

Price of hope
Lenmeldy takes stem cells from someone with MLD and uses a harmless virus to insert working copies of a faulty gene. The repaired cells are then infused back to the patient, where they begin to produce an enzyme that's lacking in children who have the disease. Some of the cells eventually migrate to the bone marrow, where they continue to live and make new cells that also make the enzyme, providing a long-lasting benefit to patients.

The first patients treated with Lenmeldy have now been followed for more than 12 years, and researchers continue to find gene-modified cells making the missing enzyme, said Orchard Therapeutics’ Gaspar.

'We can't say at the moment that this will last a lifetime, but what we can say is that there is a long-term durable effect,' Gaspar said.

MLD is an inherited disorder, and children born with it lack an enzyme needed to break down fatty substances called sulfatides. The build-up of these fatty materials eventually becomes toxic to nerves, leading to the progressive loss of movement and thinking.

Babies with MLD develop normally for a time and but then typically begin to lose the ability to walk and talk around age 2. The disease advances rapidly, causing children to deteriorate into a vegetative state.

'We are over the moon regarding what this means for other families,' said Kendra Riley, 41, of Phoenix, who has two children with MLD.

For their family, the FDA's action this week was bittersweet.

Riley's 5-year-old daughter, Olivia, is in hospice after being diagnosed with MLD as a toddler.

Riley says the first clue that something was wrong came when Olivia was around the age of 2. She began to have trouble walking, and her head started to regularly tilt to the side when she would watch TV.

'We thought we just needed some physical therapy,' Riley said.

'Then the irises of her eyes started vibrating. That's when we knew something else was going on.'

By the time doctors diagnosed Olivia with MLD, it was too late for the gene therapy to help. But knowing that the condition is inherited, they were able to get their younger daughter, Keira, tested and diagnosed.

Keira, now 4, was the 32nd child in the world to get the therapy, which is most effective before children show symptoms.

The treatment wasn't yet available in the United States, so the family crowdsourced donations to temporarily relocate to Italy in 2020 to get the therapy. It cost them about $500,000 to live abroad and pay for Keira's medical care, even though the company provided the gene therapy for free.

'Having this FDA-approved therapy means that if a child does get diagnosed before symptom onset, they have a chance at normal life,' Riley said.

'She is doing amazing. Zero symptoms,' she said of Keira. 'You would never know.'

'Exciting' drug development
The Boston nonprofit Institute for Clinical and Economic Review, or ICER, which evaluates the cost-effectiveness of new drugs, published a final report on Lenmeldy last fall and estimated that the cost of the therapy would match its expected benefits to patients if it was priced between $2.3 million and $3.9 million.

Experts agreed that even such a hefty price tag would be worth its results. Children with the disease who aren't treated usually die within five years of their diagnosis; the oldest patient to have the therapy has now been followed for more than 12 years and appears to be developing normally.

'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,' said Dr. David Rind, the chief medical officer for ICER. 'This is one of the more exciting drugs that we’ve looked at.'

Still, the Lenmeldy's price came in hundreds of thousands of dollars higher than even Rind expected.

'I think when you get into numbers this big that people don't necessarily pay attention when it gets a little bigger, but I do think this price is too high,' Rind said.

ICER gave a range of $2.29 million to $3.94 million — that doesn't mean that the top of the range is the right price, said Rind 'despite the desire by manufacturers to think of it that way.'

'Going $310,000 above the very top of that range is a lot of money,' he said.

The last product to top the charts on a per-treatment basis was another gene therapy called Hemgenix, which was approved in 2022 to treat a blood clotting disorder called hemophilia B. Its list price was $3.5 million for a one-time treatment.

Close behind that one is Elvevidys, which was approved in 2023 for muscular dystrophy at $3.2 million, and Skysona, approved in 2022 for a disease related to MLD called adrenoleukodystrophy, which costs $3 million for a one-time dose.

Even with a top-tier price, the MLD treatment will not be a blockbuster, Rind noted, because the disease is so rare. Some gene therapies approved for rare diseases have disappeared because the companies that made them couldn't make enough money to stay in business. Orchard Therapeutics has already struggled to market a previous gene therapy it developed, leaving patients hanging.

Edwin Park, a research professor at the McCourt School of Public Health at Georgetown University, worries about the impact on states, which share the cost of covering patients on Medicaid with the federal government.

Medicaid requires a minimum rebate from drug manufacturers, but without any competition, there probably won't be much negotiation about the price of the therapy, Park said.

More and more states are closely following drug pipelines after being surprised by the costs of the antiviral medications that cure hepatitis C, he said.

But even paying for one or two children to get Lenmeldy a year could be a sizeable cost for some states to absorb.

'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,' Park said.

New possibilities for patients
This latest approval comes as the FDA is working to clear a backlog of cell and gene therapies that have been waiting for its attention since the pandemic. The agency has hired more staff to review the new treatments and set up a new super office, the Office of Therapeutic Products, to oversee their regulation.

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

Dr. Nicole Verdun, who was hired to head the new FDA initiative last year, said Lenmeldy’s approval is a sign that things are moving in the right direction.

'MLD is a devastating disease that profoundly affects the quality of life of patients and their families,' Verdun said.

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

Dr. Barbara Burton, who is an attending physician, of genetics, genomics, and metabolism at the Ann & Robert H. Lurie Children's Hospital of Chicago, said it was a watershed moment for doctors, too.

'For too long, my colleagues and I have consoled families at their most vulnerable times — usually following an arduous diagnostic odyssey, coping with a dire prognosis and being told there were no treatments, and then having to watch their young child slip away.

'With this approval, we are now one significant step closer to ensuring future generations of children, families, and healthcare professionals no longer need to experience first-hand the terrible manifestations this disease has on untreated patients,' she said.

The approval of a treatment is already leading to new ways to catch the disease earlier.

Gaspar, of Orchard Therapeutics, noted that the company was supporting studies of newborn screening tests in the hopes of catching and treating the condition earlier, and screening is happening in some US states.

'Over 250,000 babies have been screened them as a result of these initiatives,' Gaspar said, and five babies with MLD have been identified. At least three of those babies have now been treated.

Riley said she wishes screening had been available for Olivia. The 5-year-old is stable for now, but Riley said she lives in fear that Keira could bring germs home.

'The common cold could kill her,' Riley said. 'So every time her sister has come home with a cold from school, that could be potentially something that takes her out.'

Olivia can't walk or talk, and she's fed through a tube. Riley says she requires round-the-clock care. Physical and occupational therapists come to the house each week 'to keep her mind moving. She does understand what's going on.'

She said that as they have watched Olivia slip away, they've come to understand that her life has had a profound purpose. But they say they hope that the approval of Lenmeldy means that no other families with MLD will have to lose one child to save another.

'We've always called Livvy 'Keira's guardian angel on Earth,' Riley said. 'She's here for a reason.'

Source: CNN