In human biology, the protein dystrophin is a shining example of Joni Mitchell’s classic line, “you don’t know what you’ve got ’til it’s gone.” Dystrophin stabilizes muscle cells. In its absence, the house of cards comes down.
For my 6-year-old son, Charlie, dystrophin will govern how long he lives. And how much dystrophin he has in his body depends on the ability of drug developers to continue improving it with innovation.
Charlie has Duchenne muscular dystrophy, a degenerative genetic disease that, until recently, has guaranteed death by early adulthood from cardiac or respiratory failure. Like all people with Duchenne, Charlie’s muscles are not coded to produce dystrophin protein, with catastrophic effects from his first days of life.
Drug discovery efforts have focused on replacing the missing dystrophin — the single root cause of Duchenne. The FDA has made significant strides in following scientific data and reason to approve new treatments by using the accelerated approval program, beginning with eteplirsen, the first treatment for Duchenne, which was approved in 2016. That decision was reinforced recently by data from the first long-term study of survival outcomes for people treated with eteplirsen. The FDA’s approval of eteplirsen showed there was a pathway for Duchenne therapies, providing children like Charlie with desperately needed help.
For parents of boys with Duchenne, dystrophin is our white whale, the life-or-death imperative no parenting manual can prepare you for. When my husband and I learned that Charlie qualified for the Phase 3 clinical trial of a gene therapy that introduces a smaller, functional form of the dystrophin gene, we did not think twice. There’s no choice between watching your child die young or pursuing a potentially revolutionary treatment. You sign the waivers and grit your teeth to support your son — still a boy, after all — in the required procedures. You make an intuitive supposition: Some dystrophin in your child’s muscles is better than none.
Science has always supported that simple theory, and the data on gene therapy’s predecessor is reinforcement. In the long-term study I mentioned earlier, eteplirsen therapy was found to increase life span by a median increase of 5.4 years — about 20% longer than the average, untreated Duchenne patient. The youngest of the boys treated with eteplirsen had 80% higher survival rates than age-matched controls.
Considering that cancer drugs that extend patients’ lives by months are celebrated, these data for a Duchenne treatment are a profound success. It demonstrates that a small amount of supplemental dystrophin — just 0.9% with eteplirsen — can meaningfully lengthen lives. Families know what those added years represent: more celebrations, more laughs, more stories. More time on this planet. I can only imagine what 50 or 100 times more dystrophin could do.
But I don’t have to imagine. That is the range of dystrophin delivery experts have measured as a result of Charlie’s gene therapy, and we see it in action every day. We usually tote a wagon on family trips so Charlie can take breaks, but on a recent trip, he refused those breaks. As I watched Charlie pace ahead of me — we logged 12,000 steps that day — I thought of all the doubts people have voiced over the effectiveness of this therapy that don’t hold up against what families like mine are actually seeing in their children. They’re walking, swimming, riding, climbing, and more — things that were once unimaginable for children with Duchenne.
Doubts about the merits of dystrophin replacement and the accelerated approval process have real consequences. They mean that for the moment, these activities remain out of reach for many families due to arbitrary restrictions on approval of this gene therapy, leaving those of us who celebrate its undeniable benefit with a form of survivors’ guilt.
The accelerated approval process exists to ensure that people with no other options get the safe, effective treatments they need, as quickly as possible. That process is rooted in logic and flexibility, and is often the only way boys like mine can access meaningful interventions. Some FDA reviewers, including the recently retired Janet Woodcock, have thankfully recognized the perils of a so-called type 2 error, where a drug’s benefits are overlooked and waiting patients are permanently harmed.
Through the initial drug reviews for HIV/AIDS — the impetus for the accelerated approval program — FDA foresight led to a flurry of approvals, evolving that condition from a death sentence to a manageable chronic disease. Put simply, innovation and drug approvals beget more and better innovation and drug approvals — with life-changing results.
The question is, will the agency support new, better, more broadly available therapies for Duchenne? Eteplirsen was just the first step. That decisive moment proved that a little dystrophin goes a long way, regardless of a patient’s age or ambulation. And that means patients and doctors are free to make treatment decisions together. Here’s what one of Charlie’s doctors says: “None of my patients have discontinued eteplirsen despite the logistics required for treatment. That tells you something. Critics should put themselves in the shoes of families and grasp how much of a difference these incremental improvements can make in real life.”
The science, tools, and knowledge exist today to expeditiously deliver medical innovations to all children with Duchenne, and to discover therapies that sustain for even longer the boys living with it. To get there, companies need incentives to keep pushing the innovation envelope. And that means the FDA must be undaunted in using accelerated approval the way it was intended.
Will giving boys with Duchenne more years of quality life be a good enough reason to act? On behalf of a 6-year-old boy whose dystrophin-infused muscles now compel him to run — whenever possible, faster and faster — I hope it will.
Jennifer Handt is a writer, communications adviser, and founder of Charlie’s Cure, a nonprofit organization that helps funds key research to find a cure for Duchenne muscular dystrophy.