- There are only 20,000 cases of Duchenne muscular dystrophy worldwide
- The FDA recently approved a controversial drug to treat the condition
(CNN)For years, Jenn McNary felt she was fighting a losing battle.
After spending four years petitioning the US Food and Drug Administration to approve the drug eteplirsen, the agency initially advised against it. It was a potential treatment for Duchenne muscular dystrophy, a rare form of the muscle degenerative disease -- the form that her two sons have.
Duchenne muscular dystrophy occurs in one out of every 3,600 male infants, and it's even rarer in girls. The deadly diagnosis is due to an inherited gene mutation, although it can be caused by a random gene mutation, too.
Boys with the condition don't produce the protein dystrophin, so their muscles are weak and can be easily damaged. Children can appear to develop slowly, and are usually diagnosed by the age of 5. Many with Duchenne rely on wheelchairs as their muscles quickly lose strength, and begin to have difficulty breathing around age 20. Many die from lung disorders within a few years after that.
There is no cure for it, but eteplirsen offered the hope of a longer, better life, and McNary -- along with other parents -- fought for it.
Late last month, the FDA finally approved the drug -- but it's not without controversy, even now. Questions remain about its efficacy, and because it targets a specific gene mutation, it will only help 13% of all Duchenne muscular dystrophy patients.
Supporters of the drug, though, believe that the technology can be transferred to other mutations, ultimately helping all patients with the disease.
A tale of two brothers
CNN first met McNary and her boys more than two years ago, when along with a small but vocal group of parents, she petitioned the FDA to approve the drug. At the time, her youngest son, Max, then 12, had been using the drug for two and a half years as part of a small trial. Her older son, Austin, then 14, didn't qualify because he was already in a wheelchair.
Most boys with Duchenne lose the ability to walk around the age of 10. At 12, Max was walking, playing soccer and riding a bike.
"You are looking at the mother of two children with Duchenne," McNary told CNN's Chief Medical Correspondent Dr. Sanjay Gupta at the time. "One who is going to have the first child survive the disease. And one who is going to have the last child die from it."
After years of back and forth between patient advocates, the FDA and Sarepta Therapeutics, eteplirsen's manufacturer, the approval felt like a win, McNary said.
Around the country, families affected by this rare disease rejoiced.
Before eteplirsen, the only approved treatment for Duchenne muscular dystrophy was steroids to help maintain muscle strength. But it also comes with serious side effects, including weight gain, which makes physical activity even more challenging, despite being necessary to maintain muscle strength.
Melanie Kelly, who also has two boys with the disease, has also been fighting alongside McNary to be heard by the FDA.
"Knowing that a drug was right there, and proven to help increase arm strength -- I don't think 'frustrating' even explains how challenging it was [that] I couldn't have it for them," said Kelly.
For the first time, now, parents say, their boys may be able to live the lives they had envisioned. While eteplirsen has no promise of reversing muscle loss, Sarepta says it may be able to slow down the disease's progression significantly, giving these boys a chance to live with a higher quality of life.
The long path to approval
The road to 'yes' was hard fought. Despite promising results from Max's trial, which began in 2012, the FDA was unconvinced of the drug's efficacy. When Sarepta proposed submitting a new drug application in 2013, the FDA said the trial was too small to show any significant improvement.
In fact, the trial was based on just 12 boys. Because Duchenne is a rare disease -- only 20,000 cases worldwide -- advocates say it is difficult to find the large numbers necessary to run large-scale, double-blind clinical trials considered the "gold-standard" by the FDA.
"Rare diseases are such that if we don't get our children in clinical trails and don't get these drugs out quickly, there's no hope for these kids," McNary told Gupta in 2014.
By definition, rare diseases result in fewer than 200,000 cases in the United States. In an effort to help people affected by them, the FDA has tried to incorporate the concerns of patients and their advocates into the approval process. In 2013, for example, the FDA established a Patient-Focused Drug Development initiative with the mission to understand the patient experience.
Between 2013 and 2015, the FDA laid out a road map so that Sarepta could determine potential new criteria that would allow for a new drug approval. It included new trials to confirm efficacy and other markers of the drugs success.
For parents like McNary, it was difficult to watch the scientific debate from the sidelines.
"We have said that we will accept the possible risk that this drug isn't as effective as it [will be] five years down the line or [that] some kind of side effect develops. But in the mean time, while [FDA officials] are not sure, while they are collecting more data, our kids are dying," said McNary in 2014.
McNary's older son, Austin, was also able to participate in one of those newly-configured trials beginning in 2014.
"I think it would help me to be able do things I like," he said of the drug then, "like playing the drums."
Today, two years later, Austin is in fact playing the drums in his school band, and also likes to play power soccer. He even skis with his wheelchair.
"I don't get tired as quickly, and I can last a lot longer in my arms. It's more upper body strength. Now I can get stuff out of my back pack," he said.
His brother, Max, meanwhile, maintains his level of energy and strength. The eighth grader sometimes has trouble with stairs, but is still independently walking.
McNary and her boys, along with other families and doctors, have continued to advocate on behalf of eteplirsen. With the FDA's recent approval of the drug, they feel vindicated.
Is it a victory?
But there are critics -- even within the FDA -- who don't see the approval as a victory.
When the FDA's advisory committee had met in April, more than 1,000 advocates also gathered, said McNary, all there to attest to eteplirsen's effect. The committee, however, voted against approving the drug, still unconvinced by the data.
Dr. Ellis Unger, the acting director of the FDA's Office of Drug Evaluation wrote (PDF), "If we were to approve eteplirsen without substantial evidence of effectiveness, or on the basis of a surrogate endpoint with a trivial treatment effect, we would quickly find ourselves in the position of having to approve a myriad of ineffective treatments for groups of desperate patients."
In a memo (PDF), Dr. Luciana Borio, FDA's acting chief scientist, said she was concerned that approving the drug could make the situation worse.
"Granting accelerated approval here on the basis of the data submitted could make matters worse for patients with no existing meaningful therapies -- both by discouraging others from developing effective therapies for DMD and by encouraging other developers to seek approval for serious conditions before they have invested the time and research necessary to establish whether a product is likely to confer clinical benefit," she said.
In a rare turn, the advisory committee's decision was overturned by Dr. Janet Woodcock, director of the FDA's Center Drug Evaluation and Research. The approval was challenged by the committee yet again; it said Woodcock was biased, in part because of her active role in speaking with patient advocates. The decision ultimately went all the way to FDA Commissioner Dr. Robert Califf, who ruled in favor of Woodcock.
In an assessment (PDF) of the disagreement, Califf said, "I believe that the quality of thinking on both sides reflects the importance of clinical and scientific expertise coupled with due process within the FDA. I find no basis for a view that Dr. Woodcock was unduly influenced by involvement with the patient community or other external pressures...in addition serious shortcomings present in the eteplirsen development program should not be allowed to establish a broad precedent for therapeutic development in rare diseases."
Emotion vs. science
So did emotions win over science?
Paul Melmeyer, associate director of public policy at the National Organization for Rare Diseases, says no. He doesn't see the eteplirsen decision as a precedent, but rather, the course of action the FDA has taken during the past 15 years to incorporate the views of patients and their advocates.
"There's only so much you can understand by looking at the data and the statistics. If you finally hear from patients about what kind of risk they are willing to take, we believe that really allows FDA reviewers to have a really full picture," said Melmeyer.
The drug won't be cheap. It's expected to cost close to $300,000 each year, but because there are so few cases of Duchenne, it is expected that much of it will be picked up by insurance companies.
While McNary's boys are already on the drug, she's excited to see it made available to others. Indeed for parents like Kelly, for example, the approval could open a new chapter in their lives. She and her husband have already contacted their insurance company to obtain the drug for their sons, 16-year-old Liam and 19-year-old Jacob.
"I can barely contain myself," Kelly said of the approval.
She believes eteplirsen's approval could usher in new therapies and potentially even a cure for the Duchenne.
"It's so exciting," Kelly said. "We want every single boy and girl to get it -- my goal in life, so that no one ever hears...'Your son has Duchenne.' "