LEANDER, Texas — Andrew Revell leaned into his father as he pulled up from his wheelchair to stand, his legs trembling with effort. It had been more than a year since he joined a clinical trial for a gene therapy to treat the disease that is destroying his muscles and cutting short his young life. Had it made a difference? He didn’t think so.

“I didn’t really get the medicine,” Andrew, 18, said at his home in Texas on a recent July day.

“We don’t know,” Laura Revell, his mother, interjected.

“Yeah, we don’t know,” Andrew agreed. Doubts about whether he got the real gene therapy or a placebo in 2024 have haunted the Revell family for months. In October of this year, Andrew would get a second infusion, and if he had received the placebo the first time, he would be guaranteed to get the medicine.

But that is no longer guaranteed.

The deaths of two teens who received the gene therapy to treat Duchenne muscular dystrophy caused its manufacturer, Sarepta Therapeutics, to pause the clinical trial and, under pressure from regulators, halt all shipments of the drug this month. News of the deaths has rocked patients with Duchenne, a rare genetic disease that afflicts an estimated 15,000 people in the U.S., the vast majority of them boys and young men like Andrew and his brother, Timothy, 21.

Tim and Laura Revell have chosen not to tell their sons about the latest controversy, preferring not to crush their hopes while Sarepta faces off with an increasingly skeptical Food and Drug Administration. The FDA announced Friday night it was investigating a third death of someone who received the gene therapy, called Elevidys. The 8-year-old boy died June 7, the agency said. Roche, which sells the therapy overseas, stated the physician treating the boy in Brazil “assessed the death as unrelated” to the drug.

The uncertainty about the dangers of the therapy exposes the difficult decisions facing families, biotech firms and regulators as they balance the hope for treatments against the risks of speeding drugs into the marketplace with ambiguous data about how they perform. The FDA approved Sarepta’s gene therapy for Duchenne, and later expanded it, despite clinical trials that failed to meet their main functional goal and concerns among the agency’s own reviewers about its effectiveness.

‘The pinnacle of life’ , A profitable therapy , ‘Most impressive safety’ , A change at the FDA , ‘There’s nothing out there’

Two boys died after a gene therapy. This family won’t give up hope.

Timothy and Andrew Revell sit in the dining area at their home. The family is concerned that they may not be able to get access to a gene therapy after two patient deaths related to the treatment.

The extremely costly drug has been approved by the FDA since 2023. Andrew is part of a clinical trial testing the drug for a subset of patients who are unable to walk.

Time is working against the Revells. The median survival age for a young man with Duchenne is about 28, meaning Andrew, who has a soft spot for Super Kitties coloring books, and Timothy, whose face is framed with peach fuzz, might be well past the middle of their lives.

The disease that has already robbed them of the ability to walk is eating away at their muscles, making it harder for them to lift their arms. But buoyed by faith and the prospect of getting the gene therapy, they are hopeful for the future.

“I want to get married someday,” Timothy said.

“Me too,” Andrew added.

Tim Revell also has a way of seeing his family’s trials in the brightest possible light, given the historical lack of treatments for Duchenne.

“It’s actually a good thing we have to worry about our kids dying from this product, because it means we have a product to be worried about,” he said. “If you don’t do anything for a young man with Duchenne, he’s going to die.”

‘The pinnacle of life’

Tim and Laura Revell met while working at Domino’s Pizza in their teens. They reconnected after a chance encounter between classes at community college, and married just after graduating from the University of Texas at Austin. When Timothy was born in 2003, Tim said, “it was the pinnacle of life.”

Timothy’s development traced an arc familiar to Duchenne families: He struggled to get up from the floor. He was slow to walk. One day when he was almost two, Timothy broke down in tears while on a walk with his parents and could go no farther, his parents recalled. It wasn’t a typical toddler tantrum and they knew something was seriously wrong. A blood test soon confirmed it.

“Go and love on him,” Tim Revell recalls being told by the doctor. “But he won’t make it past 20.” Andrew was born with the same genetic mutation.

Family photos decorate the wall at the Revell home.

Baseball memorabilia at the Revell home. Andrew and Timothy Revell are ardent baseball fans and like to play “MLB Rivals” on their phones.

Andrew could still play baseball when he was 14, but his running around the bases became more of a walk. Timothy hit his physical peak around age 10, after which he needed a couch to pull himself up from the floor.

“It’s just so hard to watch your child lose the basic makeup of humans, which is movement,” Tim Revell said. He’s run a marathon every year since that first diagnosis, helping the family raise more than $8 million for CureDuchenne to support research into the disease.

Duchenne has left its imprint on every surface of their lives: the single-story home with wide corridors, custom-built to accommodate Andrew and Timothy’s physical limits; the thermoses with built-in straws that enable them to drink water without having to lift it to their lips; an “Elevidys” sticker casually left beside a partially-built Lego project.

At times, as Andrew and Timothy bantered about baseball standings and played the game “MLB Rivals” on their phones on a recent Tuesday, it was possible to forget that they were any different from other sports-obsessed young men. Then their bodies would deliver a reminder.

“Hey Mom, can you scratch the side of my head real quick, please?” Timothy asked in his soft drawl. “Can you scratch the side of my head real quick?”

“Which side?” Laura Revell said, making her way over to where Timothy sat in his wheelchair. “You want to do it with your hand?” she asked, guiding his fingers to his temple.

A profitable therapy

Duchenne was once a backwater in biotechnology because it afflicts relatively few people. But that has begun to change, driven by parent advocacy groups and the arrival of gene therapy.

The disorder stems from a genetic mutation that prevents the body from producing dystrophin, a protein whose tiny coils function like a shock absorber for muscle cells. Sarepta’s therapy inserts a DNA sequence into the body that makes a shortened form of dystrophin, aiming to slow the destruction of muscle.

More than half a dozen publicly traded companies are working on Duchenne treatments, and Sarepta has led the way, bringing three drugs to market before its gene therapy won FDA approval.

Sarepta CEO Douglas Ingram’s compensation in 2022 was valued at $124.9 million, making him one of the one most highly paid CEOs in America that year. With Elevidys selling for $3.2 million a dose, the drug has brought in more than $1 billion in revenue in just over a year.

But Elevidys’s path to FDA approval was contentious. In its first major randomized clinical trial, the therapy failed to show that boys who received it performed better on a battery of physical tests than those who got a placebo.

Sarepta decided to seek accelerated approval, designed by the FDA for drugs that treat patients suffering from severe diseases with few effective therapies. Instead of having to prove that its gene therapy directly benefited patients, Sarepta argued that the presence of its engineered dystrophin in their muscle tissue was likely to benefit them.

“We’d have to hide our tears and look away from each other when we’d see Brecken struggle to walk up the stairs,” Marit Sivertson told the panel, referring to her son. After participating in Sarepta’s clinical trial, she said, her son “is living the life that every sweet 9-year-old boy ought to be living.”

Sheila Ungerer reveled in her son Will’s ability to do normal kid things after getting the experimental drug, like riding a bike without training wheels.

“I’m hoping that people will step away from genuflecting to statistical rigor,” said Kathleen O’Sullivan-Fortin, an advocate for patients with a rare genetic disease and one of the 14 voting members of the panel. The drug seemed to be safe, she said, adding that “dragging our heels seems like it’s doing harm.”

But other panel members were unconvinced that the drug worked. Because Duchenne boys can get a gene therapy only once, those who get Sarepta’s medicine would be closing the door on others in development.

Without more evidence, there was a risk that the boys might take “a potentially ineffective gene therapy with the associated risks, including liver and cardiac problems,” said panel member Lisa Lee, who specializes in scholarly integrity at Virginia Tech.

The committee favored approving it 8-6 in a nonbinding vote. But the FDA’s reviewers recommended against approving the drug, concluding the data didn’t prove it was effective. They were overruled by their boss, Peter Marks, director of the Center for Biologics Evaluation and Research, who granted accelerated approval for children ages 4 and 5 who could still walk.

Marks explained in an interview that Sarepta’s evidence and the lack of options for Duchenne patients justified approving the drug.

“We have to advance in gene therapy, and the data supported it,” he said.

Sarepta set its sights on expanding the population who could get Elevidys, starting a clinical trial for patients such as Timothy and Andrew who could no longer walk.

But the Revell family faced an anguishing choice: Sarepta had space for Andrew in the new trial. But Timothy, who had been in a cell-replacement trial years earlier, was disqualified.

The boys are each other’s closest companion. They share a full-size bed, divided down the middle by a ridge of stuffed animals.

“What do we do for Timothy?” Tim Revell said. “His brother’s going to get something and he’s got nothing, and he is older.”

‘Most impressive safety’

In June 2024, a year after Elevidys’s initial approval, the FDA’s Marks once again set aside a negative recommendation from agency staff and approved expanding the drug to all kids at least 4 years old with the Duchenne mutation, including those who could not walk.

By then, Andrew had enrolled in the clinical trial and received his first dose. Now Timothy, too, might be able to get Elevidys.

Then in March of this year, Sarepta disclosed that a 16-year-old boy who could not walk had died after receiving the drug. The virus used to transport the gene therapy into muscle cells is likely to have triggered an immune response in the liver, Sarepta has said, causing inflammation that led to liver failure.

Ingram, Sarepta’s CEO, defended the drug’s safety in a call with financial analysts in May, saying Elevidys has “one of the most impressive safety profiles” among its kind of gene therapy “that has ever existed.” He added that there was no reason to think that the FDA “would be considering anything other than the fact that they should be proud that they approved this brilliant therapy.”

Throughout Sarepta’s clinical trials, there had been relatively little debate about its safety. Novartis, Pfizer and others have used the same type of virus used to transport their gene therapies, and the risk of serious liver injuries was well-known.

A vial containing the active ingredient of Elevidys for the treatment of Duchenne muscular dystrophy is labeled at the Roche Diagnostics plant in Baden-Württemberg, Germany, in February 2024. (Uwe Anspach/Picture Alliance/Getty Images)

Sarepta had found that liver injury was a common side effect of Elevidys, but the patients had recovered after treatment. There had been no deaths until the 16-year-old boy this year.

The second death was announced on a Sunday in June, barely a month after Ingram’s comments. A 15-year-old boy had succumbed to liver failure after his infusion. He was in the same clinical trial as Andrew Revell.

Tim Revell got the news at 7:20 a.m. It was Father’s Day.

Both patients who died were teens whose disease had progressed to the point they could no longer walk, like Andrew. But for Tim Revell, the worst news wasn’t about the drug’s safety. He worried more about access.

“It may not even be available,” he thought.

A change at the FDA

Fallout from the second death was swift. Sarepta’s stock price, which had fallen more than 60 percent after the first death, dropped 40 percent. Physicians wrestled with the emerging safety risk. And while Sarepta pointed out that death was a rare outcome among more than 900 patients who had received it, more families began canceling appointments to get Elevidys as they confronted the emerging risk of death, the company acknowledged.

Louise Rodino-Klapac, Sarepta’s president of research and development, said in a July 7 interview that deaths sometimes happen as a drug is administered to a broader patient population. “Patients are coming, asking really good questions,” she said. “Ultimately, in the vast majority of times, they are still choosing to dose with Elevidys.”

The fallout has dealt a blow to Sarepta’s finances. The company said it would lay off 36 percent of its workforce on July 16 to “support its long-term financial viability.”

The Sarepta Therapeutics headquarters in Cambridge, Massachusetts, on Wednesday. Sarepta reversed its stance and said the company will pause all shipments of Elevidys. (Cassandra Klos/Bloomberg/Getty Images)

Douglas Ingram, CEO of Sarepta Therapeutics, speaks at a health care summit in 2023. (Michael Nagle/Bloomberg/Getty Images)

Two days later, Ingram was trying to quell investor panic after reports that another patient had died of liver failure in a Sarepta trial for a different gene therapy. The CEO again projected confidence that the FDA would not change how Elevidys could be prescribed.

But the FDA leadership had changed. Marks was gone. Replacing him was Vinay Prasad, who had criticized Marks after the first death linked to Elevidys for green-lighting a drug “that seems to be killing children and blowing their livers up.”

On July 18, about four hours after Ingram’s comments to analysts, the FDA asked Sarepta to halt all doses of Elevidys, including for patients who can walk. Sarepta refused, saying it saw no new safety risks for ambulatory Duchenne patients.

Over the weekend, Sarepta executives reconsidered. On Monday evening, the company reversed course, agreeing to the FDA’s request to halt all Elevidys shipments in a bid to salvage its relationship with the agency. “It became obvious that maintaining that productive working relationship required this temporary suspension,” Ingram said in a statement.

The FDA didn’t respond to a request for comment.

‘There’s nothing out there’

Marks, who left the FDA in March, defended his decisions on Elevidys but said that the deaths from liver failure must be investigated further.

In hindsight, he said he might have asked Sarepta to gather more data on non-walking patients before expanding Elevidys’s approval, but added the safety risk might not have emerged even with additional testing.

“Do you hold back?” he said. “Those boys, there’s nothing out there for many of them.”

For now, it is unclear when Elevidys will be available. As of July 25, Tim and Laura Revell had not told Andrew and Timothy that all dosing of the drug had been suspended.

Timothy and Andrew know only about the first death, from March, and hold on to hope that Elevidys could transform their lives.

“It will help me scratch my head on my own, hopefully,” Timothy said.

Andrew is hoping it will help “get my arms back to being stronger, lifting them higher up and helping my heart stay stronger.”

Occasionally, they indulge in a hope that no current therapy can offer.

“To walk again someday,” Timothy said. “And we won’t be in wheelchairs anymore.”

His parents are clear-eyed about the drug’s risks and limitations. “We know it’s not the best product,” Tim Revell said. “We know it is not going to help Timothy and Andrew walk again.”

But they don’t correct them.