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The Future of Medicine Is Unfolding Before Us. Are We Nurturing It?
Feb. 19, 2024, 5:02 a.m. ET
A flowering planet trapped by an encasing glass barrier, preventing it from growing further.
Credit...Kaitlin Brito
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By Elizabeth Currid-Halkett
Dr. Currid-Halkett is a Guggenheim fellow and professor of public policy at the University of Southern California.
On Jan. 8, 2020, as I was parking my car, I got a long-awaited phone call from one of my son’s doctors. She informed me that our 7-month-old son, Eliot, had Duchenne muscular dystrophy, a fatal neuromuscular disease.
I can still remember the way the Los Angeles winter sunlight hit the dashboard. I can see my neighbor walking up her steps with groceries, a leaf falling, oblivious to the devastation below. “Life changes in an instant,” Joan Didion wrote. “The ordinary instant.” Our son had a fatal illness. He would die before us.
D.M.D. prevents the production of dystrophin, a protein needed to protect and repair muscle cells. It is caused by a genetic mutation on the X chromosome, thus the disease almost exclusively affects boys (one in 3,300). Over time, children with D.M.D. lose muscle mass and thus the ability to do basic things like run and walk. Eventually they lose their ability to breathe and they experience heart failure. There is no known cure. While existing treatments have helped extend the life span of sufferers they mainly focus on managing symptoms.
In my search for answers for how to save my son, I contacted Dr. Jerry Mendell, a now-retired neurologist at Nationwide Children’s Hospital in Columbus, Ohio, who was running clinical trials for an experimental gene therapy he developed to enable dystrophin production in boys with D.M.D. The treatment, now known as Elevidys, offered the prospect of not merely managing symptoms, but slowing the disease’s progression or even stopping it in its tracks — and potentially, for the first time in the history of this terrible disease, allowing boys with D.M.D. a chance to thrive.
Since I had that first conversation with Dr. Mendell (also a senior adviser for Sarepta, the maker of Elevidys), clinical trials for the gene therapy have had their ups and downs, and some adverse effects have also been reported. But in June 2023, based on a two-part clinical trial, the Food and Drug Administration granted accelerated approval for the treatment for 4- to 5-year-olds who do not have other disqualifying conditions. The F.D.A.’s approval was contingent on continuing trials showing evidence of improved motor function, which had not yet been established.
Before Eliot received his treatment, he had difficulty going up stairs. He complained about being tired after walking only a block or two, even on Halloween when candy ought to have motivated him. Hopping on one foot, a milestone for a 4-year-old, was impossible.
On Aug. 29, he finally received the one-time infusion. Three weeks later, he was marching upstairs and able to jump over and over. After four weeks, he could hop on one foot. Six weeks after treatment, Eliot’s neurologist decided to re-administer the North Star Ambulatory Assessment, used to test boys with D.M.D. on skills like balance, jumping and getting up off the floor unassisted. In June, Eliot’s score was a 22 out of 34. In the second week of October, it was a perfect 34 — that of a typically developing, healthy 4-year-old boy. Head in my hands, I wept with joy. This was science at its very best, close to a miracle.
But the goal to offer this possible future to more patients with D.M.D. is in jeopardy. Sarepta is seeking F.D.A. approval to treat boys over 5. Disagreements over the latest clinical trial’s results threaten to derail that outcome.
Moreover, what the F.D.A. decides to do next with Elevidys could set the tone for how it handles other emerging gene therapies for rare diseases. We can already see roadblocks that prevent more families from gaining access to these new treatments — from high costs and insurance challenges, to dissent over how flexible regulators should be in interpreting clinical trial results and taking qualitative improvements into account. What is at stake with the debate around Elevidys is more than just the chance to give other boys with D.M.D. a more normal life. The challenges that we are witnessing with Elevidys are a harbinger of the fights we may see with gene therapies developed for other rare diseases.
There’s an opportunity to reduce those barriers now, while these treatments are still in their early phases. Every child afflicted with a life-threatening disease deserves the chance Eliot has been given.
The biggest obstacle to getting these treatments is cost. Gene therapies cost, on average, between $1 million and $2 million. At $3.2 million per patient, Elevidys is the second-most-expensive drug in the world. Insurance companies would probably prefer not to foot the bill, and without full F.D.A. approval, insurance companies can refuse to cover these treatments by claiming they are medically unnecessary or experimental. Before Eliot’s treatment began, my own insurance company initially said it would cover the cost but then started stalling on coverage and questioning the urgency of Eliot’s treatment. I was able to call Dana Goldman, the dean of the Sol Price School of Public Policy at the University of Southern California, where I work, to help me navigate the process. I was in the rare position to marshal resources and assistance to pressure my insurance company into covering Elevidys. Across the country, physicians are fighting denials and seeking appeals for their young patients.
Dr. Goldman has argued that one way to incentivize insurance companies to cover the high costs of treatments like gene therapies is to amortize how much the companies pay over time if the effectiveness of such treatments do not last (analogous to a “pay for performance” model). Another option is for pharmaceutical companies to offer a warranty that gives a prorated refund to the insurance company if a patient needs to return to prophylaxis treatment within a certain number of years. Costs are an especially frustrating problem for rare diseases like D.M.D., where the extremely small patient population deters companies from investing money and resources to develop new treatments. Some experts believe the federal government ought to do more to directly complement research funding for rare diseases, as it has through the Orphan Drug Act for over four decades. The government could also defray the cost to consumers by offering subsidies directly to patients.
There’s another big role the government can play to accelerate gene therapies besides intervening in costs — and that’s to make the wheels of regulatory approval for these drugs less onerous. Flexibility doesn’t have to come at the cost of safety. The F.D.A. acted swiftly to approve an antiretroviral drug for H.I.V. in the 1980s, and the Covid vaccines in December 2020, each saving millions of lives without putting people in harm’s way.
But Elevidys is a case study in how the F.D.A. can get in its own way. D.M.D. patients 4 to 5 years old did receive access to the drug under fast-tracked approval, the first time a drug was approved under this new framework. But this was reportedly only because Peter Marks, the director of the F.D.A.’s Center for Biologics Evaluation and Research and Evaluation, disagreed with his own staff’s rejection. Current concern over Elevidy’s approval for boys over 5 focuses on the most recent clinical trial results that showed older boys, whose muscular decline is further along, did not improve on motor function as measured by the North Star Ambulatory Assessment after treatment. However, as Sarepta has noted, they still saw gains in their ability to rise from the floor and walk 10 meters, indicating possible slowing of the disease that could significantly improve and extend their lives.
Detractors suggest this improvement is not enough to meet the bar for approval. This is a common problem for rare disease trials because they often consist of very few participants. In such cases, a narrow focus on numbers ignores the real quality-of-life benefits doctors, patients and their families see from these treatments. During the advisory committee meeting for Elevidys in May 2023, I listened to F.D.A. analysts express skepticism about the drug after they watched videos of boys treated with Elevidys swimming and riding bikes. These experts — given the highest responsibility to evaluate treatments on behalf of others’ lives — seemed unable to see the forest for the trees as they focused on statistics versus real-life examples.
The F.D.A. can have a more flexible view of treatment efficacy without losing focus on safety. As with any drug, whether for migraines or asthma, there will be a spectrum of effectiveness. The same will be true of all gene therapies, and the F.D.A. should reconsider the metrics it uses to green-light these treatments now, before it potentially leaves thousands of patients in the lurch, out of access to something lifesaving.
Gene therapy is the future of medicine. But our bureaucracy and insurance companies should not hinder patients from receiving pioneering treatments that could transform their lives. As parents, we are not asking for the moon. We just want our children to live.
Elizabeth Currid-Halkett is a Guggenheim fellow and professor of public policy at the University of Southern California.
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