Three years ago, the FDA made one of the most polarizing decisions in its history. It approved a drug for the rare genetic disease Duchenne muscular dystrophy on the slimmest of evidence, a watershed moment that caused a highly publicized rift within the agency.
In the midst of it all were parents who pushed hard and advocated like never before, even making public presentations to the FDA, under the agency’s new willingness to hear public and patient input.
Some of that patient input included data, gathered through videos and interviews with caregivers, that seemed to show kids in the trial improving after taking the drug, known as eteplirsen (Exondys 51). These detailed personal accounts were compiled independently; neither eteplirsen’s developer, Sarepta Therapeutics (NASDAQ: [[ticker:SRPT]]), nor the FDA had them.
Top FDA officials said those data didn’t influence their decision. After the approval, head drug evaluator Janet Woodcock spoke at a conference with one of the Duchenne parents, Christine McSherry, and said that her data, collected from her son and other patients in the eteplirsen trial, weren’t rigorous enough.
But then Woodcock said something surprising: If they could better quantify the results and have their methodologies validated by a federal Institutional Review Board, the data could be extremely useful.
So McSherry and Mindy Leffler, another Duchenne advocate who helped gather the data, decided to start a company. Their startup, Casimir Trials, is working with a dozen drug makers, among them Sarepta, to compile data that show the impact rare-disease medicines might be having on patients.
Casimir’s goal is to address a frustrating gap. Patient experience seems to demonstrate that an medicine might be working, but the “hard” clinical data, approved as part of the study’s design, might show no effect whatsoever.
“We are tired of hearing parents saying, ‘Oh my gosh, I swear that drug was working, I swear he was walking better or he ran better,’ and then the drug gets put on the shelf because it didn’t meet its primary endpoint,” McSherry tells Xconomy.
Ten years ago, maybe even five, the idea of a patient advocate supplying important data to the world’s most powerful drug agency would have been ludicrous. But Casimir’s progress illustrates so much about big changes in the way biomedical science and its regulators have recently evolved.
In the past, “people have tended to consider these [types of data] to be ‘soft’ outcomes,” says Harlan Krumholz, the director of the Center for Outcomes Research and Evaluation at Yale-New Haven Hospital. But “what is ‘hard’ data anyway, except that it is reproducible and it triangulates with other information that we know about people in ways that make us believe it’s valid?”
Casimir’s efforts are worth watching as more and more rare-disease drugs come to market—including, potentially, a group of gene therapies for Duchenne that are in human testing. One method Casimir and its tech partner, iTakeControl, have developed to study patients’ ability to move over time is under FDA review, McSherry says. If approved, the measure could be used as a study goal in future clinical trials. McSherry and Leffler mentioned that goal at a meeting held Thursday (pictured above) by the Institute for Clinical and Economic Review (ICER), the nonprofit drug pricing watchdog.
In a research note following the meeting, RBC Capital Markets analyst Brian Abrahams noted that this “type of endpoint could potentially be explored by Sarepta” in its Duchenne gene therapy trials to “further support approval and eventual reimbursement.” Sarepta isn’t currently working with Casimir in its gene therapy trials, says spokesperson Tracy Sorrentino. But McSherry says the two are “in discussions” about the possibility. (They are already working together in at least one other trial, she says.)
The FDA doesn’t comment on discussions it has with companies, says spokesperson Sandy Walsh. But Walsh did confirm that conversations took place between McSherry and Woodcock, and that “the FDA is very much in favor of seeking to measure, in a reliable way, outcomes of interest and value to patients.”
Filling the Gap
Duchenne is a deadly genetic disease that afflicts some 300,000 kids worldwide who can’t produce a shock-absorbing protein known as dystrophin. Without dystrophin, their muscles gradually waste away, beginning with their legs. They often can’t walk by their teenage years and die at a young age because of heart or lung problems.
Before eteplirsen, which treats a small subset of patients and is meant to slow the progression of the disease, there were no FDA-approved treatments for Duchenne. A steroid sold by PTC Therapeutics (NASDAQ: [[ticker:PTCT]]), deflazacort (Emflaza), has since been approved for Duchenne patients as well. But there still is no cure.
McSherry’s son Jett—one of her five children—was diagnosed with Duchenne at the age of five. As McSherry explained in this 2018 podcast, the pain of hearing the diagnosis was so severe that “you could think of nothing else but wanting to die.” But she turned those emotions into
