When Pat Furlong’s two sons were diagnosed in 1984 with Duchenne muscular dystrophy, a rare genetic disease that usually leaves boys wheelchair-bound by their teens and dead by their 30s, doctors told her there was nothing they could do.
“It’s heartbreaking,” said Furlong, the founder and president of Parent Project Muscular Dystrophy, the nation’s largest nonprofit organization focused on Duchenne. “You have no options.”
That might be beginning to change, at least for some families.
On Tuesday, and again in January, a Food and Drug Administration advisory committee will consider whether to recommend approval of two drugs to slow the muscle deterioration at the root of Duchenne. If approved, the medications would become the first treatments for a condition that affects an estimated 1 in 3,500 boys.
“It’s really a momentous time,” said Louis Kunkel, a Harvard geneticist, credited with discovering the gene behind Duchenne, who has long helped search for treatments. “For years, we’ve been able to do nothing for these families and their children. . . . I thought we would have cracked this nut a long time ago.”
Duchenne is caused by a mutation in the gene responsible for producing dystrophin, an essential protein involved in muscle function. Without dystrophin, even routine activities can damage muscles, causing them to die and be replaced by fat and other tissue. Boys typically receive a diagnosis by age 6, and the disease’s steady progression leaves many of them immobile by the time they are teens. It eventually affects the heart and respiratory muscles, making breathing difficult.
Both drugs the FDA will evaluate in the coming months use “exon skipping,” an approach intended to bypass the faulty genetic code and restore the ability to produce dystrophin. But Duchenne patients and their families know that even if the FDA decides the drugs are safe and effective enough to approve — an outcome that remains far from certain — they aren’t a silver bullet.
At best, the drugs can help boys produce enough dystrophin to transform Duchenne into a milder and more sustainable form of muscular dystrophy known as Becker. In addition, only about 13 percent of Duchenne patients have the particular mutation that could allow them to benefit from the drugs.
FDA staffers already have raised serious concerns about the treatment that advisers will consider on Tuesday, a drug known as drisapersen that’s owned by California-based BioMarin. A review posted online Friday detailed the “contradictory” effectiveness data for the drug, as well as “life-threatening” safety risks such as severe kidney damage and low blood platelet counts.
The families of boys who have received eteplirsen, made by Massachusetts-based Sarepta Therapeutics, have been particularly vocal supporters, taking to Facebook and YouTube to post videos documenting the apparent halt in their sons’ decline. They’ve also petitioned the White House, visited lawmakers on Capitol Hill and made their case to top FDA officials that the unmet medical need posed by Duchenne warrants an approval based on the clinical evidence that already exists.
Even so, the FDA has raised questions about the methods the company has used to measure dystrophin, as well as the small initial sample size — there were 12 boys in the original clinical trial, four of whom received a placebo.
Despite whatever reservations federal regulators might have, parents and advocates in the Duchenne community have made clear they are willing to accept a high level of risk in exchange for the potential benefits, particularly when the alternative is a slow decline followed by death. They want what they’ve never had before: options.
“I think everybody is holding their breath right now. There’s a whole lot of hope, especially among the parents who have sons on these trials,” said Debra Miller, whose 19-year-old son, Hawken, has the disease but would not benefit from the drugs. Miller and her husband in 2002 founded the national nonprofit CureDuchenne, which has helped fund the development of both drisapersen and eteplirsen.
Miller said approvals from the FDA, should they come, would serve as an important signal that treatments can be developed for Duchenne. It could spur more investment in research and give a boost to treatments already in the pipeline, including a gene therapy and other drugs under development by the likes of Pfizer and Eli Lilly.
“It [would give] the boys hope that they will have a life,” Miller said. “That they should go to college. That they should go ahead and get braces on their teeth. That they will have a future. That we can find a cure for this disease.”
Billy Ellsworth, of Pittsburgh, wants that sort of future. One of the 12 boys enrolled in the original trial for Sarepta’s eteplirsen drug in 2011, he will turn 15 in January. While other Duchenne patients his age have become dependent on wheelchairs, Billy still gets himself out of bed each morning, heads downstairs on his own for breakfast, puts his dishes in the sink. He can still brush his teeth without help. He walks unassisted into the hospital each week to receive his infusion of eteplirsen.
“He’s like a little walking miracle,” said his mother, Terri Ellsworth, who feels certain the experimental drug has altered her son’s life for the better. But while she’s thankful for Billy’s reprieve, she has mixed emotions. She knows many other patients and their families who are desperate for treatments.
“It’s historical, it’s exciting, but it’s also wrought with anxiety. We don’t know how the FDA is going to rule,” she said of the upcoming hearings. “Ultimately, our community wants both drugs approved, so that parents have a choice.”
For Pat Furlong, whose sons died in the mid 1990s, the FDA milestone is bittersweet. Like other parents who have lost children to Duchenne, she’s thrilled this moment has arrived, but wishes it had come far earlier.
“There’s never a day I don’t wish my sons were here and could have an opportunity to take advantage of what we know now,” she said.
Furlong also said that despite her delight over the possibility of the first approved treatment for Duchenne, she thinks often of the parents and boys who aren’t in the 13 percent of patients who might benefit from the two drugs awaiting a decision by the FDA. No matter what the agency decides, their wait continues.
“It’s both hope and heartbreak,” Furlong said. “There’s not a parent on this earth with this diagnosis that hasn’t asked themselves repeatedly: Will what my son needs arrive in time?”
