Billy Ellsworth works on social studies lessons at home in Coraopolis, Pa., March 27, 2014. He is part of a clinical trial for eteplirsen, a drug that has not only slowed the progression of Duchenne muscular dystrophy, but also improved his symptoms. (Rebecca Droke/Pittsburgh Post-Gazette/MCT)
Most boys with Duchenne muscular dystrophy are in a wheelchair by 15 and in a casket before 30. Parents want to know then, why hasn't the US FDA approved an experimental drug that could save their sons?
A wheelchair by age 12, maybe 15 if he were one of the lucky ones. A ventilator would be next, and then would come the casket, probably before he turned 30. That was what Terri and Bill Ellsworth expected for their son when doctors confirmed his diagnosis of Duchenne muscular dystrophy, a debilitating and fatal disease striking one in 3,500 boys.
Instead, Billy has become an active, happy teenager who likes to dance to Beatles songs, walk around at classic car shows, hike on local trails, and jog in his living room along with avatars of Michael Jackson and Elton John he created for his Wii video game. He’s like a lot of other 13-year-olds but for an awkward gait, and the Wednesday afternoons he spends at Children’s Hospital of Pittsburgh for an infusion of an experimental drug that’s keeping his disease at bay – and without any side effects.
Billy, of Coraopolis, Philadelphia, is one of a dozen Duchenne patients who are receiving eteplirsen as part of a clinical trial. The drug was expected only to slow the progression of the disease, but Billy and others in the trial are finding their symptoms are improving. Testing confirms that their lungs are getting stronger and their bodies are producing dystrophin, an essential protein that wasn’t present in muscles biopsied two and a half years ago when the trial began.
Results astounded researchers. “I’ve done many, many clinical trials and never encountered one that was so clean, effective and very well tolerated,” says principal investigator Dr Jerry Mandell, Ohio State University professor of medicine and director of gene therapy at Nationwide Children’s Hospital in Columbus, where testing was initially conducted. For the 12 boys and their families, it’s a miracle drug. But other Duchenne patients can’t access it because the Food and Drug Administration (FDA) hasn’t yet approved it.
Terri Ellsworth and other mothers are lobbying regulators to expedite approval under a 2012 law that encourages faster reviews of breakthrough therapies that address unmet medical needs for rare and life-threatening diseases. They spent the past month collecting signatures on a petition they sent to the White House urging the administration to expedite approvals of drugs that treat Duchenne muscular dystrophy. The White House has promised to respond publicly in writing to petitions with at least 100,000 signatures. The Duchenne petition reached that threshold a few days ago.
Duchenne parents believe eteplirsen meets all the requirements for expedited approval, and they’re urging action now because their children are running out of time. They were hopeful last July when the FDA expressed interest in eteplirsen, but were disappointed when the agency came back three months later and paused the process, saying government scientists needed more data from drug developer Sarepta Therapeutics. The Massachusetts-based company is awaiting more direction from the agency.
“FDA’s drug approval process requires well-controlled clinical trials that provide the necessary scientific data,” agency spokeswoman Sandy Walsh said in an email message, noting she couldn't discuss specific cases under review. “If a drug product is to be marketed, well-controlled clinical trials are needed to ensure that the drug is safe and effective when used as indicated.”
The issue seems to be the size of the sample, not the quality of the research, says Mandell. He knows his trial was small, but its results were clear. All 12 boys showed increased dystrophin production and clinical improvement or stabilisation well beyond expectations for patients whose muscles normally degenerate rapidly. “We didn’t breach any acceptable protocol. Everything was done according to the way it should be done,” Mandell says.