The Fight to Pay for Gene Therapy

There is new hope for seemingly incurable diseases, but the treatments will be truly revolutionary only if they are available to everyone.

“I was a really, really sick kid,” said Kyle A. Smith, who underwent his first surgery at 3 months old after sickle-cell disease caused blood to become trapped in his spleen. He estimates he has been hospitalized hundreds of times, and his mother often had to take him to the prestigious Children’s Hospital of Philadelphia in their hometown. He spent much of his youth in extreme pain due to a genetic mutation that affects the body’s hemoglobin. His red blood cells take on a rigid sickle or crescent shape and don’t deliver enough oxygen, causing anemia. The misshapen cells also get caught inside the veins and arteries, blocking blood flow and causing inflammation, swelling, and pain.

“These pain crises can happen wherever blood flows,” Smith said. “It’s unfortunate that you can experience pain pretty much everywhere within your body.” Though pain is a known consequence of sickle-cell disease, he said doctors don’t always take him seriously when he needs opioid treatment, which is the standard for care. Most people with sickle-cell disease are Black, like Smith, or brown, and racism can be a serious barrier to pain management in particular. Smith said doctors have accused him of being a malingerer, and he got used to suffering in silence. “It teaches you at a very young age that you have to really, really be your biggest advocate and the fiercest champion for yourself to be able to adequately receive the type of treatment you deserve,” he said.

The roughly 100,000 Americans who live with the sickle-cell disease have a few treatments at their disposal. Thanks to recent medical advancements, the median life span for sufferers is now somewhere in the mid-40s, according to Dr. Lewis Hsu, chief medical officer for the Sickle Cell Disease Association of America. Smith, who is 35, takes ​​hydroxyurea, which can help prevent the formation of sickle-shaped cells. A bone-marrow transplant can help the body produce healthy red blood cells, but there’s a problem. “Not everybody has a donor,” Hsu said.

Now, science offers patients fresh hope. In December, the FDA approved two new gene therapies for the treatment of sickle-cell disease, Casgevy and Lyfgenia. Both therapies are made from a patient’s stem cells, and each treatment alters the body so it begins to produce a healthy form of hemoglobin. Casgevy uses CRISPR, the gene-editing technology, to cut and then edit DNA to create modified stem cells. Lyfgenia uses a virus to deliver these cells directly into the body. Both treatments require patients to undergo a round of chemotherapy to strip any unhealthy cells from the bone marrow before the treated stem cells are transplanted. No bone-marrow donor is required. In clinical trials, Casgevy and Lyfgenia were found to be both highly effective and potentially curative, offering patients freedom not just from pain but from stroke, infection, and organ failure.

“Just the idea of an opportunity to lessen your pain and have less crises and less hospitalizations is always appealing,” Smith said. But he is undecided about gene therapy, and its cost is one reason: Casgevy is priced at $2.2 million and Lyfgenia at $3.1 million. He said he worries that his insurance company won’t cover the full price of treatment.

Scientists have been working on gene therapy for decades, and the past several years have seen one breakthrough treatment after another — for a form of congenital vision loss, for beta thalassemia, even for some cancers.  Gene therapies could transform lives, but they won’t truly be revolutionary unless they are available to all, and the American health-care system is not so egalitarian. The U.S. doesn’t guarantee health care to everyone, and insurance companies often refuse to cover even the most routine procedures.

There is some good news, however. Gene therapies have high price tags, but they may be more cost-effective than conventional treatments for some conditions, including sickle cell and a form of hemophilia. Insurance companies have announced plans to cover the new therapies, too, yet some patients and families say they’ve still had trouble finding coverage. Science is changing, but one basic fact remains the same: In the U.S., getting health care often means putting up a fight.

Though I don’t have sickle-cell disease, Casgevy and Lyfgenia excite me because they make me wonder if someday there will be a gene therapy for my own rare disease, a condition called hereditary spherocytosis. My red blood cells are shaped like spheres and break down too quickly. This process can cause a rare form of anemia, which makes me tired, and my spleen is enlarged, which can be painful. The condition also causes gallstones and jaundice. Unlike sickle-cell disease, hereditary spherocytosis doesn’t affect my life span or put me in the hospital very often. Although I’ve had doctors question my pain and fatigue, I haven’t experienced medical racism.

At the time of my diagnosis, I was a broke college student ready to graduate into poverty. After school, my health insurance covered so little that I tried to avoid the ER even if I was in pain. The Affordable Care Act wasn’t safe yet, so for all I knew, my genetic disease would become the ultimate preexisting condition and prevent me from ever getting decent insurance. The future seemed bleak. Fifteen years after my diagnosis, the ACA is settled law, and I have good insurance. I have a minimal co-pay to see my hematologist, I was able to afford my gallbladder surgery, and, despite the anemia, my health is generally good. But I remember my early experience with a rare disease, and I have long wanted to know whether gene therapies will be affordable for everyone who needs them.

I reached out to Dr. Aaron Kesselheim, a professor of medicine at Harvard Medical School and a faculty member at Brigham and Women’s Hospital, who told me gene therapies carry high price tags for several reasons. The U.S. allows drug companies “to charge whatever they want for their products and put various restrictions on payers’ abilities to negotiate,” he said. That means brand-name drugs cost at least twice as much here as they do in countries that can negotiate drug prices “based on the clinical benefits that the drug provides and its available alternatives,” he added. Prices may be onerous for insurers, whether they are private or public payers like Medicaid.

The high price of gene therapy could deter patients from pursuing the treatments. “If we’re talking about a $2 million treatment, I would assume that a large portion of that would not be covered by insurance and left up to patients and their families to figure out how to foot that bill,” he said. That may not happen, but Smith isn’t alone in his worry. “There needs to be serious consideration to how to do this with reducing some of those costs,” said Dr. Alexis Thompson, the chief of the Division of Hematology at the Children’s Hospital of Philadelphia. “I can see that there are many families, even as they are reading news reports about gene therapy, becoming dismayed almost immediately when they hear about the price tag.”

Insurance companies are taking steps to cover gene therapies, though Kesselheim said the process varies from company to company. “A lot of them are covering it with requirements for prior authorization to make sure the person who is undergoing the gene therapy qualifies based on the clinical trials,” he explained. Other insurance companies “are trying to negotiate with the manufacturer to pay over time or with payments based on the possibility that the treatment will persist over time, and if it continues to work, another installment will be made.”

Last year, the FDA approved Elevidys to treat Duchenne muscular dystrophy in patients ages 4 and 5. In some cases, though, the companies initially denied the treatments, which forced parents to file appeal after appeal before their sick children aged out of treatment. Insurance problems still persist, as Elizabeth Currid-Halkett recently told the New York Times. A professor of public policy at the University of Southern California, she said her own insurance company agreed to cover the drug for her son but then began to stall, “questioning the urgency” of his treatment. “I was in the rare position to marshal resources and assistance to pressure my insurance company into covering Elevidys,” she said in a recent Times editorial. Those resources aren’t available to many parents.

In the case of sickle-cell disease, more than half of patients appear to be on Medicaid rather than privately insured. Last month, STAT News reported that the Centers for Medicare & Medicaid Services announced it would negotiate directly with Vertex Pharmaceuticals and Bluebird Bio, which produce Casgevy and Lyfgenia, respectively. Under the agreement, Medicaid would be required to cover the therapies, but if they don’t work as promised on a given patient within a certain time frame, the manufacturer would issue a rebate to Medicaid.

As insurers reckon with the costs of gene therapy, hospitals have stepped forward to help their patients. When Richelle Brooks of New York learned that her newborn son, Conner, had a form of adrenoleukodystrophy, a disease that damages the white matter of the brain, she feared the worst. “When I Googled ALD … nightmare images, nightmare stories of all these boys becoming vegetative and dying,” she told me. Genetic testing would later reveal that her oldest son, Jayden, had ALD too. Though MRIs show no progression of the disease in Jayden, Conner wasn’t as fortunate. His family considered a bone-marrow transplant to treat the condition but said their hospital in Rochester didn’t feel equipped to perform the procedure for ALD. Brooks and her family decided to go to Boston Children’s Hospital instead, though it was some distance from their home.

Then came another blow: Dr. Christine Duncan of Boston Children’s told her Conner didn’t have a perfect donor match, so he was ineligible for the safest type of transplant. But Brooks knew the FDA had just approved Skysona, a gene therapy for Conner’s form of ALD. On the phone with Duncan, she began to cry. “‘Richelle, I know. I’m sorry, I feel like I’m giving you blow after blow,’” Brooks said Duncan told her. “I said, ‘Dr. Duncan, I’m crying because any day before today, this would’ve been devastating news.’”

Still, there remained the problem of cost: Skysona is priced at $3 million, and the family would potentially be going out of its insurance network for care. “The doctors told us, ‘Don’t worry about insurance. That is not your job. That is ours. Come to Boston, we’ll take care of it,’” Brooks said, adding that several senior leaders at Boston Children’s contacted Highmark Blue Cross Blue Shield to make sure the company would cover the treatment.

Duncan, who is the Boston Children’s director of clinical research and clinical development for the Gene Therapy Program, said patients and families face “multiple hurdles” to care: “A team has to work with your insurance company, figure out what the approvals are, if we need to do anything, and how we can advocate for patients. All the providers I know, myself included, are happy to get on the phone and try and explain to people because, in my experience, insurance has never tried to deny people. It’s just a hard topic.”

Hospitals do have a financial incentive to ensure coverage of these treatments, according to Kesselheim. “Gene therapies are largely administered as in-hospital procedures, which can sometimes include multiple-day stays,” he explained. If an insurance company denies gene therapy, it will likely “also reject all the related hospital costs.”

Gene therapies are typically available in only a few select hospitals across the U.S., meaning patients and their families often have to travel for care, which also means they may have to pay for flights, hotels, and child care — and potentially miss work. (Because New York has paid family leave, Brooks said she didn’t incur the usual financial penalty for missing work.) Boston Children’s defrayed some expenses for the Brooks family by providing food vouchers and parking passes in addition to a weekly caregivers’ lunch.

Conner finished treatment on March 16, 2023. He’s the first person in the world to receive Skysona outside a clinical trial, and his mom says he’s feeling great. Though he had to start kindergarten a year late, he’s now doing well in school. He is active and loves playing Roblox. His disease has not progressed.

Conner’s story could reassure some patients for whom price is one factor to consider among many. For instance, gene therapies for blood disorders may be curative, but patients must be monitored for years to make sure that the treatment is effective and that serious side effects haven’t developed. They can temporarily lose bone-marrow function, making them susceptible to infection. There’s a risk of infertility and possibly cancer, “not only from the chemotherapy that is used for conditioning but perhaps from the process itself,” said CHOP’s Thompson. At Boston Children’s, Duncan said they would not push gene therapy on a patient if that’s not what they want: “But for many of these diseases, the natural history of the disease is worse than even the things they’re up against, and they have a choice.” That’s new. Even five years ago, patients with diseases like cystic fibrosis or sickle cell had few options for treatment. “So even though this is difficult,” Duncan added, “I’m very hopeful.”

So is Smith. Although he is still trying to decide if gene therapy is for him, he knows what it means to the broader sickle-cell community. In 2020, he helped launch the Crescent Foundation to care for sickle-cell patients. Working with his co-founders, who also live with the disease, Smith organizes volunteers to transport patients to local hospitals and educate medical students about the reality of life with the condition. He hopes to address housing insecurity next, a common problem for people with sickle cell.

“I think I would be open to it, which is to say a lot,” Smith said of gene therapy. The side effects and potential complications concern him — and so does the prospect of lost income. There are so many factors to consider, he told me. “But the benefit is an extension of life for potentially ten, 15, 20 years,” he said. “The benefit is not having to feel any more pain crises. The benefit is to not have to be admitted into the hospital so frequently and for it to disrupt your life so tremendously.”