In mid-July, Kristen Secrist hopped on a call with her 5-year-old son’s doctor, who had urgent news: The first gene therapy had been approved for Duchenne muscular dystrophy. Her son, Hiram, would be a perfect candidate — if, she added, they could get him dosed in time.
The treatment was approved only for 4- and 5-year-olds. Hiram turned 6 in three weeks.
“Oh, crap,” Secrist said to herself.
When the Food and Drug Administration OK’d Sarepta’s gene therapy, Elevidys, on June 22, it set off a race at a handful of neuromuscular centers across the country: Could they identify, screen, secure insurance for, acquire drug product for, and dose their oldest 5-year-olds before they became ineligible?
It was a very different challenge than the nation’s top Duchenne doctors expected to face this summer. Sarepta had asked the FDA to grant the one-time therapy accelerated approval — a form of provisional authorization — for virtually all patients with the fatal, muscle-wasting disease who could still walk, which would have meant most boys under the age of 12.
Duchenne is one of the most common rare diseases, with perhaps 500 U.S. children diagnosed every year. Neuromuscular centers tried to figure out how they would handle the rush. They held mock run-throughs. They made lists and tried to figure out who to prioritize: The oldest, who were nearing wheelchairs, or the youngest, who would benefit the most? They considered lotteries.
Then Peter Marks, the agency’s head of biologics, OK’d the drug only for a narrow age range. It was a compromise position. Despite powerful anecdotes, the data Sarepta produced were mixed. Marks wanted to ensure access for patients with the clearest results while Sarepta finished a larger trial. (His reviewers wanted to reject the drug outright.)
Doctors sat down with families of boys ages 6 and up who had placed their hopes in the treatment and explained it would take a while longer.
“They’re very, very tough cookies,” said Emma Ciafaloni, a neuromuscular specialist at Rochester University. “So it’s a difficult conversation, but they also have a very deep understanding. And I think that they also hope that there is going to be some other opportunities.”
More pressing were the edge cases: what to do with patients technically eligible but already out of time. They understood why the FDA restricted the label. A clinical trial had shown dramatic benefit for 4- and 5-year-olds, but not for 6- and 7-year-olds. But the borders bothered them. Was a patient who was 5 years and 11 months so different from a patient who was 6 years and a day?
“It’s arbitrary,” said Ciafaloni, who has worked on Sarepta trials. “Very, very arbitrary.”
Although only a small group of boys are affected, the problem could reappear. Marks has campaigned on using accelerated approval more broadly for gene therapies for rare disease, in which the window for intervening is often narrow. Another gene therapy, Zolgensma, approved in 2019 for spinal muscular atrophy, has an age cutoff at 2, and doctors say they sometimes still miss patients.
That could make it important to establish newborn screening for Duchenne and other rare diseases. Today, some boys are not diagnosed until after their 6th birthday.
Sitting in her Virginia home, Secrist tried to remember what she learned in therapy: about separating the things she can control from the things she can’t. OK, she could take him in for the appointments. She could only hope insurance coverage and the drug itself came before it was too late.
About a month before Secrist’s call, Leigh Ramos-Platt, head of the neuromuscular clinic at Children’s Hospital Los Angeles, got a call from Sarepta. She had been preparing for Elevidys since January, assembling a hospital-wide team to coordinate dosing for at least a dozen patients. But now, she was chiefly concerned about one boy: Damon, who would turn 6 on July 7.
Ramos-Platt had told Damon’s mom, Rosario Mateo, about the therapy a couple months before. She was eager. Damon was doing well by all accounts, an artistic child who would sit with his mom at their home west of downtown Los Angeles and sketch hummingbirds and other animals, summoning images on his iPad as inspiration. And his particular mutation made him eligible for one of the handful of approved Duchenne therapies.
Still, that drug was only modestly effective, and it required weekly infusions. Sometimes, Damon cooperated for the hour. Sometimes, he didn’t. Either way, his family watched the boy’s arms swell with bandages and bruises.
“It’s heartbreaking,” Mateo said.
In late May, Sarepta indicated an approval was likely coming but with the age restriction. Ramos-Platt called Mateo in mid-June and explained that things had changed but she had spoken with Sarepta and it was trying its best to prioritize boys like Damon.
Now, days before approval, the company officials called again: There was no chance of getting the drug to Damon in time.
“I think they were sincerely very sad about it. And, you know, I was too. I think our whole team was and definitely the family was,” said Ramos-Platt. “It’s an awful situation to be in where you have an approved drug and I can’t give it. Can’t give it.”
The officials could only explain the holdup when the approval came.
Gene therapy is not a pill. It consists of trillions of small, gene-carrying viruses directly infused into a patient. Before approval, Ramos-Platt needed to ensure she had different specialists prepared to monitor the various potential side effects. The pharmacy needed to do run-throughs for handling the product, which comes in dozens of vials that have to be stored and thawed at particular time points and temperatures.
“This is in some ways like organ transplant,” said Sarepta’s chief customer officer, Dallan Murray.
Sarepta had worked for months to make sure hospitals were ready. But it couldn’t speed the last part. Synthesizing viruses is tricky business, more complex and mistake-prone than producing the small molecules that comprise most medicines. To confirm every dose had the right amount of gene-carrying virus and minimal contaminants, both Sarepta and the FDA had to individually review measurements on each lot before it could go to hospitals. The agency wouldn’t sign off on the first lot until July 18.
Ramos-Platt broke the news to the family. Technically, she could still prescribe the therapy. Medicines are routinely given “off-label.” But she knew payers were unlikely to cover off-label use of such an expensive product — Elevidys costs $3.2 million — and she had her own reservations about giving a new complex therapy, with serious potential side effects, outside of FDA guidelines.
She explained that data from a clinical trial in the fall could lead the FDA to expand the label. It provided some comfort. Mateo said she’d keep praying. All this was better than the word she had gotten when Damon was diagnosed at age 2, her concerns tripped by motor delays, and was told there were no treatments available. (The drug Damon takes was approved in late 2019.)
Still, she knows the trajectory her son is on. The gene therapy might slow muscle degradation but it cannot reverse what’s lost. “The [muscle] breakdown doesn’t wait,” she said.
Cash Huber got closer. Four days after the approval, his dad, Phil, rushed him an hour from their home in Delaware to the Children’s Hospital of Philadelphia, a major gene therapy center, to do preliminary tests. They had to make sure his blood didn’t have antibodies against the gene therapy virus and set a functional baseline to measure improvement after treatment.
Phil and his wife, Jena, had placed their hopes in gene therapy since Cash was diagnosed at age 2. They tried prednisone, the steroid commonly used to slow the disease. But it led to “crazy” temper tantrums, Phil said. When Cash was 4, they traveled to Norfolk, Va., to enroll him in a clinical trial but he narrowly missed the stringent screening criteria.
“We were just racing, trying to get all of our ducks in a row,” said Phil.
His birthday was July 17, but his doctor, Susan Matesanz, was optimistic. Sure, the timing was tight, but in clinical trials, patients can be dosed so long as they’re screened and enrolled while they’re in the eligible age range. Some doctors and advocates hoped it would be the same for the commercial market.
Cash cleared the tests. Then they sent the paperwork for insurance: Highmark Delaware, through Jena’s job as a dental hygienist.
It was denied. The therapy, the insurer said, was experimental. They appealed and got the same answer. Matesanz asked to speak with a medical reviewer, a process called peer-to-peer, but said she was put in touch with an adult emergency health physician, rather than someone with pediatric neuromuscular experience.
“They basically said it’s ruled experimental,” she said. “Here are your next steps for appeal. And it wasn’t any more of a conversation than that.”
Highmark’s chief medical officer, Timothy Law, declined to comment on Cash Huber’s case, citing patient privacy, but said in an email “it is not uncommon for insurers to consider a new treatment experimental and investigational until it displays more substantial real-world benefits” and that “coverage positions may change over time” as new data become available.
Kelly Maynard, who runs Little Hercules Foundation, a nonprofit that helps Duchenne patients access medicines, said Blue Cross Blue Shield subsidiaries such as Highmark have long limited access to drugs granted accelerated approval. But with past Duchenne drugs, she has almost always been able to obtain coverage on appeal.
“This case … is the first time I have seen an external reviewer uphold the denial for a patient that’s in-label,” she said.
Secrist’s phone buzzed on Thursday, July 27. With three children running around, she ducked into the laundry room. It was her life-changing moment room. Three years before, she had stood there distraught as a doctor, looking over lab results, explained via phone her son’s diagnosis.
Now, she started crying — but happily. Sarah Wright, Hiram’s physician at Children’s National Hospital, told her he could be treated. The drug was available. The hospital’s finance division had just learned that insurance would cover it. She had refused to let herself believe it would happen.
“I don’t know what kind of magic they were doing behind the scenes,” she said.
They scheduled an appointment for the following Wednesday, a day before Hiram’s 6th birthday. In the meantime, he started high-dose steroids, meant to mitigate his body’s immune response to the virus. Wright reminded them of the follow-up they were committing to: weekly check-ins for at least two months, to monitor potential side effects.
On Friday, July 28, Sarepta’s manufacturing partner, Catalent, assembled a kit at its Philadelphia facility containing the precise number of vials needed for Hiram’s weight.
On Monday, the company dispatched it by plane to a pharmacy in Illinois that specializes in handling gene therapies. Later that day, it was flown to D.C. and put on a delivery van to Children’s National.
Throughout its journey, it was kept at minus-80 degrees. Murray, the Sarepta executive, tracked each step on a monitor from Cambridge, Mass., the drug’s temperature-controlled container equipped with sensors that let him track tiny details like whether the package was tilted.
“Every step of the way, I’m on pins and needles,” he said. “There was no margin for error.”
On Tuesday, at 10 a.m., Wright and a team sat around a table and reviewed every detail of the process. Secrist, meanwhile, held an early celebration for Hiram, giving him presents and cake, afraid that side effects might prevent him from celebrating on the day of.
The family arrived at the hospital early Wednesday morning. Hiram was dosed midday. He played Lego Star Wars on his Nintendo Switch as viruses coursed through muscles, another doctor’s visit for a boy who had many. He had asked to wear his “future paleontologist” T-shirt. Secrist found it fitting.
“I remember thinking he’s just so brave and he doesn’t even know it,” Secrist said.
They stayed in the hospital all afternoon just in case. Elevidys can induce vomiting and liver damage, among other side effects. But nothing popped up.
Hiram, it turned out, would not be an exception. Hours after he was dosed, Sarepta revealed on an earnings call that numerous boys about to turn 6 were scheduled to receive treatment. Hospitals had worked overtime to get them ready. Insurers had largely come through, with UnitedHealthcare agreeing to cover it and multiple state Medicaid systems indicating they would do the same, swayed by the data and the need.
The swiftness surprised Sarepta executives, as well as advocates like Maynard of the Little Hercules Foundation.
“What we’re seeing right now is not what I’m used to,” she said.
She suspects insurers believe the therapy could save them in the long term, deferring costs of hospital visits and equipment like wheelchairs and ventilators that most Duchenne patients will eventually need. At many insurers, though, the jury is still out. Aetna told STAT it had yet to make a decision. Humana did not respond to a request for comment.
Cash Huber’s family learned about Hiram through a social media group Secrist set up to help other families navigate the process. It brought them both joy and pain. It felt like the “Hunger Games,” Phil said, with some families getting drugs, while others, like theirs, hitting a wall.
They and other families are hoping the results from the ongoing trial will persuade the FDA to expand the approval, although they know that’s not certain. In the meantime, they’ve continued to fight, retaining a lawyer and contacting lawmakers in hopes of pressuring Highmark. But it’s an unlikely battle, especially with Cash now weeks on the other side of 6.
They celebrated that birthday with a big party at their home: 45 to 50 guests, cake and ice cream around the pool, a bounce house for the kids. Phil watched, unsure how to feel. Lately, Cash had started to notice the difference between himself and other boys. He had come home from a field day at school, angry they could do things he couldn’t.
It had forced Phil into a difficult conversation, the first but probably not the last.
“God,” Phil thought at the party. “I wish you were turning 5.”
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