As Sarepta Therapeutics moves closer to full approval and an expanded label for its gene therapy, some experts push back on clinical efficacy and cost while others note the hope it provides patients with Duchenne muscular dystrophy.
Sarepta Therapeutics is anticipating full FDA approval and a label expansion for its gene therapy, Elevidys, with the company indicating on its Q1 earnings call last week that a draft label is imminent. But the therapy has come under the microscope regarding its high cost and clinical effectiveness.
Elevidys, which won accelerated approval for Duchenne muscular dystrophy (DMD) patients aged 4 to 5 in June 2023, has benefited Sarepta economically, pulling in over $200 million in 2023 and another $133.9 million in the first quarter this year. Whether it is of benefit to patients, however, depends on who you ask.
High Demand for Elevidys
DMD is one of the more severe forms of inherited muscular dystrophy, according to the National Institutes of Health. The disease is caused by mutations in the dystrophin gene, leading to muscle fiber degeneration and weakness. Debra Miller, CEO of CureDuchenne, told BioSpace that Elevidys, the first gene therapy for DMD, has been “tremendous” for families enrolled in trials and has demonstrated positive effects for patients.
Michael Kelly, the organization’s chief scientific officer, added that the FDA was “super brave” and made the right decision in giving Elevidys accelerated approval. “There is an enormous appetite in parents whose children are 4 to 5 to get access to this drug, and there is an equally enormous appetite for younger children . . . to get access to this drug. We’ve seen many examples of families that have undergone treatment and [are] seeing real, measurable benefits,” Kelly told BioSpace.
Uy Ear, vice president of U.S. healthcare—biotechnology at Mizuho Securities, told BioSpace that Elevidys’ uptake had been “pretty incredible.” However, Ear said that DMD patients are usually diagnosed at close to five years of age—close to the cutoff for Elevidys. Patients are aging out of the therapy, and Sarepta is essentially running out of patients, Ear said, so a label expansion is needed to get more patients on the treatment and continue the forward momentum.
Sarepta is looking to expand access to Elevidys to DMD patients without an age restriction or ambulatory status.
According to Ear, if the FDA does grant full approval and a label expansion, the impact will be significant for DMD patients. “Many parents and physicians, in general, believe that you need to treat these patients as early as possible and as quickly as possible, primarily because as each day goes by . . . they lose muscle, and you want to preserve this,” he said.
Kelly added that full approval would allow for an easier pathway for other drugs in the pipeline for DMD to get approved.
Benefit and Cost of Elevidys Questioned
But while some experts are bullish on approval, others have cited potential drawbacks and concerns about the gene therapy. David Rind, the chief medical officer of the Institute for Clinical and Economic Review (ICER), penned an article in JAMA last week in which he noted that Elevidys missed its primary efficacy endpoint in two studies but still netted approval.
In briefing documents released prior to the May 2023 advisory committee meeting for Elevidys, the FDA stated that the measurement of levels of micro-dystrophin in the muscle tissue only provided information about the “expression of the transgene product in cells transduced by [the therapy], rather than insight into a pharmacologic effect on a biomarker in the pathway of the disease.”
While acknowledging its potential, Rind told BioSpace it is too early to determine if micro-dystrophin is an effective biomarker.
“You’d like to know that micro-dystrophin has some effect on Duchenne muscular dystrophy before you call it a surrogate,” he said. “Normally, when we imagine a surrogate, there has been some connection between the thing you’re measuring and an outcome you care about. . . . Here, it’s a brand-new protein with no evidence that it affects the course of Duchenne muscular dystrophy, so it’s not a reasonable surrogate endpoint.”
Rind recommended the FDA insist on a carefully controlled, longer term or larger trial in order to determine if Elevidys is beneficial, “rather than accepting a therapy that failed in its clinical endpoints.”
In the JAMA article, Rind also called out the $3.2 million per dose price tag for the gene therapy as a significant point of contention. He said there is no scheme in the U.S. to deal with pricing issues.
It would be “unfortunate” if the FDA does move forward with an expanded indication, but it seems like a distinct possibility, Rind said.
Kelly said that while he understands the regulatory issues surrounding the therapy, there has been benefit reported by patients and parents. Ear noted that it is still too early to know what major issues or downsides exist with Elevidys, but that no major safety concerns have arisen to date.
“If you believe the videos and the parent reports and the doctor reports of how incredibly effective this gene therapy is, it’s hard to explain why it failed in this clinical trial,” Rind countered. “If it’s that good, why weren’t the primary outcome measures able to show that?”
Sarepta did not immediately respond to a request for comment from BioSpace.
Overall, experts are anticipating that the gene therapy will get across the final finish line, and Kelly said it would be “difficult to swallow” for the DMD community if a full approval and eventual label extension is not granted.
“Give the patient the choice in making the decisions and the treatment options,” Kelly said. “The families and individuals here are particularly well versed of the limitations [of the therapy].”
Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.patchen@biospace.com. Follow him on LinkedIn.
