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Does Muscular Dystrophy Drug work? Advocates Pack FDA Meeting

Sarepta Therapeutics New Global Headquarters

Jack Willis, center, Nolan Willis, right, and Max LeClaire, bottom, are all afflicted with Duchenne muscular dystrophy. They attended the opening for Sarepta Therapeutics new global headquarters in Cambridge on June 2, 2014. Boston Globe / Boston Globe via Getty Images

Billy Ellsworth reads quickly but barely stumbles as he reads a brief statement pleading for approval of an experimental drug he has been taking since 2011.

"FDA, please don't let me die early," he says.

It's a dramatic moment in a hearing packed with dramatic moments. Billy, 15, joined a long line of patients, families and advocates urging the Food and Drug Administration to approve the drug to treat muscular dystrophy.

FDA advisers were clearly affected by this kind of testimony, presented at an daylong hearing at a hotel just outside Washington, D.C., but they voted to reject approval of the drug.

The FDA usually follows the recommendations of its panels. Monday's vote was not decisive. Seven of 13 advisers voted against approval, three voted for it and three abstained, saying they couldn't decide either way.

"I also was moved by the testimony," said Dr.Paul Romitti, an epidemiologist at the University of Iowa and a panel member. "As much as I'd like to say yes, I'm uncomfortable with the evidence to date."

This hearing is just the latest to show the effects of the FDA’s efforts to give patients a bigger voice in the drug approval process. This time, that patient voice has the help of several high-octane public relations firms and is encouraged by the success of a big PR effort to back the controversial approval of Addyi, a female libido drug okayed amid considerable media coverage last August.

FDA officials are worried about a repeat of accusations that they were pressured by the coverage.

This time, they say they’ll listen to the patients, while not being unduly swayed by the emotional appeals of the parents, patients and advocates. Many of the advocates accuse the FDA of unfair bias against the drug.

“It is not the volume of the message, but the content. We listen and listen closely," Dr. Billy Dunn, director of the FDA division of neurology products, said in opening the hearing.

The FDA is considering a drug aimed at just 13 percent of muscular dystrophy patients. It’s a highly tailored therapy that uses a completely new approach to treating the condition.

Muscular dystrophy is a catchall term for a group of genetic diseases that gradually disable kids. Most patients are boys. Some die young as the muscles that control breathing break down, while others may live long lives with only moderate disability. There’s no cure for any form and not even a real treatment, although steroids and physical therapy can help.

The drug in question is called eteplirsen. It’s aimed at a mutation seen in a subset of children with Duchenne muscular dystrophy, a degenerative disease that causes muscles to break down because cells produce faulty versions of a protein called dystrophin, or none at all.

Eteplirsen, made by a small company called Sarepta Therapeutics, uses an approach called RNA antisense to cause the body to “skip over” the mutation that causes the disease, as cells “read” the DNA to do their daily work.

The hope is that skipping over the mistake would help cells start making normal dystrophin again. But it’s not clear it actually does that.

Sarepta Therapeutics New Global Headquarters
Jack Willis, center, Nolan Willis, right, and Max LeClaire, bottom, are all afflicted with Duchenne muscular dystrophy. They attended the opening for Sarepta Therapeutics new global headquarters in Cambridge on June 2, 2014. Boston Globe / Boston Globe via Getty Images

Sarepta’s chief medical officer Dr. Edward Kaye says the company has shown this. “These data clearly indicate that eteplirsen is working as intended,” Kaye told the packed-out hearing.

Dr. Jerry Mendell, who helped run the clinical trials of the drug at Nationwide Children’s Hospital in Columbus, Ohio, says he’s seen no evidence the drug has any side-effects and showed images of Billy walking in a marathon. “Usually boys this age with Duchenne muscular dystrophy don’t walk,” Mendell said.

“I can’t see any grounds for withholding this drug for Duchenne muscular dystrophy boys.”

But FDA officials say the evidence the company has presented is not clear at all. They’re not sure that the 12 boys tested are producing dystrophin. They are also not fully convinced by videos that show the boys walking.

The boys were not treated in what’s called a randomized trial — there were not untreated boys with similar backgrounds used to compare what happens when some get the drug and some do not. So the agency and its expert advisers have to just look at what happened before and after treatment, a notoriously unreliable way to assess how or whether a drug is actually working.

Billy's mother Terry Ellsworth traveled from Pittsburgh, her bill paid for by an advocacy group, to accuse the FDA of bias. "The committee has been tainted and led astray," she testified, before stepping aside to let her son speak. "I am afraid that if you do not approve this drug I will weaken and not be as independent as I am now," Billy said.

“The FDA is certainly keen on looking at the data in different ways,” Dr. Ronald Farkas, who’s helping lead the FDA team evaluating the drug, told the hearing.

Farkas, clearly aware that he was speaking to a hostile crowd, said repeatedly the FDA was not trying to keep a good drug off the market.

“I think that you haven’t heard the whole story. But I really want to reassure everybody that I will remain open to what I hear from the community,” he added. “I have made no final decision.”

Farkas he said he and other experts cannot tell whether the boys tested were being helped by the drug. Different patients are affected differently by muscular dystrophy, he said.

Dr. Janet Woodcock, a senior FDA official, noted that the FDA does worry about approving a drug that doesn’t work.

“There often is little consideration of another error — which is failing to approve a drug that actually works,” she added. “But most of this consequence is borne by patients who have little say.”

Advocates note there is nothing at all for muscular dystrophy patients.

“We fully understand that eteplirsen is not a cure and that it only slows progression of disease,” said Christine McSherry, whose Jett Foundation is named for her 20-year-old son who has muscular dystrophy.

“The collective evidence suggests to us that eteplirsen is having a real and concrete effect on disease.”

And McSherry noted the extreme need. “Jett took his last step when he was 13,” she said. Not only do patients then have to use wheelchairs, but this can over time affect their spines and their ability to breathe.