relentless advocacy. A registered nurse, she started the nonprofit Jett Foundation in 2001 in an effort to save Jett’s life.
“Every parent who has a child with a deadly disease, they really do think they can conquer the world,” McSherry says on the podcast.
Jett lost the ability to walk around the age of 15. As his condition worsened, McSherry’s foundation got stronger. She raised some $20 million to fund research and promote awareness, and she worked her way to the forefront of a movement for patient and advocate empowerment. Jett was enrolled in a clinical trial of eteplirsen, and McSherry lobbied for the FDA to review the drug.
That was a controversial quest. Sarepta had an unusually contentious relationship with the FDA as it tried for years to get the agency to approve the drug on an “accelerated” basis, based on the amount of dystrophin patients taking its drug were producing. The only data the FDA had on eteplirsen before approval came from a tiny, 12-patient clinical trial.
Those scant data compared patients on eteplirsen to a “historical control”—previous data from patients deemed to have similar characteristics to those who took the drug. The study did not compare its patients to those receiving a placebo, which the FDA usually prefers. This clinical scenario typically wouldn’t even get a look from the FDA, but a number of factors changed the equation—among them, arguably, pressure from a very mobilized patient group.
In September 2016, the agency approved eteplirsen because it “demonstrated an increase in dystrophin production” that was “reasonably likely” to produce a benefit.
The decision was so contentious that it caused infighting at the FDA. Opponents were worried of setting a precedent that “pressure and even intimidation—not science—guides FDA decisions,” according to an agency document released following the eteplirsen decision. Some staffers were critical of Woodcock, who championed eteplirsen and was backed by then-FDA commissioner Rob Califf.
The story was a litmus test for the increasing power of patient advocates and their impact on drug approvals, a complex and controversial topic given that many groups receive funding from drug makers. (Here’s more on pharma/patient group relationships from a 2018 Kaiser Health News report.)
Sarepta priced its drug at an average of $300,000 per year, based on a patient’s weight. Convincing payers to cover the drug “has been difficult, there’s no question about it,” says Parent Project Muscular Dystrophy founding president and CEO Pat Furlong. That’s in part because Sarepta still doesn’t have clinical data proving, definitively, that eteplirsen benefits patients.
Drug-price watchdog ICER argued in a draft report earlier this month that “no persuasive evidence yet exists” to demonstrate eteplirsen’s clinical effectiveness. “Eteplirsen has been on the market for three years, and yet we still found notably inadequate data on patient outcomes,” said ICER chief medical officer David Rind in a prepared statement at the time.
Thursday’s meeting convened to elicit a variety of perspectives, including that of patient advocates, before ICER issues its final report about eteplirsen’s price relative to its perceived effectiveness. The report could have consequences. The patient community is concerned that a negative ICER review—which insurers have increasingly valued—will make it even harder for them to get access to the drug, McSherry says.
Yet McSherry swears by eteplirsen. Jett has been taking the drug for years. He can smile fully now, she says. He opened a beer bottle on his own for the first time. (He’s 22 years old now.) He stopped snoring because he’s breathing better at night. These are improvements that as a young man with Duchenne, Jett wasn’t likely to achieve on his own, she says. Yet they weren’t reflected in Sarepta’s data. And that disconnect was reflected at the ICER meeting Thursday, she says.
“The biggest takeaway was the lack of outcome measures that are relevant and meaningful to patients with Duchenne,” McSherry said after the meeting.
Casimir aims to fill this gap by using video to catch changes, over time, in the quality of patients’ movements, rather than, say, how fast they can walk in six minutes or how long it takes for them to get up off the floor. Are they no longer using two hands to grab a bannister and pull themselves up the stairs, for instance? Are they compensating for their weakness in other ways, like swinging one of their legs out to climb a step? The goal is to pick up subtle changes that wouldn’t be detected on timed tests. “It’s not how fast you move, but how well you move that is the difference, especially in Duchenne,” McSherry says.
The information-gathering process the FDA is reviewing from Casimir involves shooting videos of activities in patients’ homes then uploading the information to cloud-based databases. Physical therapists would review the video and issue scores based on whether patients are using compensatory factors—like using one’s arms to make up for weak leg muscles.
Sarepta spokesperson Sorrentino confirmed that the company is working with Casimir on a study called LEAP. Casimir’s videos are being used alongside standardized clinical tests, as Sarepta outlined in this poster. The LEAP trial is evaluating both eteplirsen and an experimental drug called golodirsen that is currently under FDA review.
McSherry says Casimir has contracts with others in the Duchenne space but declined to name them. McSherry and Leffler—who wasn’t available to comment for this story—want to go beyond Duchenne and apply their methods to evaluate drugs for Huntington’s disease, rare forms of epilepsy, and other conditions, in ways that standardized tests may not capture.
“We want to get to the truth of what’s happening when we give these kids with rare diseases drugs,” McSherry says, “and the benefit that patients and caregivers find meaningful.”
