As a crucial deadline nears for a closely watched regulatory decision, two Republican senators are urging the Food and Drug Administration to approve a controversial drug to treat Duchenne muscular dystrophy.
In a letter sent last Friday, the senators expressed “disappointment” that an FDA advisory panel last month voted not to recommend eteplirsen to combat the disease, which is a rare and fatal genetic disorder that causes muscles to waste away. About 13,000 children, mostly boys, are afflicted and they typically die before turning 25 years old. The panel determined the drug was not effective.
The FDA is scheduled to decide whether to approve the drug, which is made by Sarepta Therapeutics, by this coming Thursday. And its decision is being closely watched as a litmus test for the agency, which is grappling with increasingly assertive patient groups that want the agency to take a more expansive view toward approving medicines for unmet medical needs.
In this instance, patient advocates and their many backers want the FDA to use what is called the accelerated approval process to endorse eteplirsen. This approach relies on a substitute outcome in a clinical trial to suggest a drug may have, but does not guarantee, a benefit. The senators maintain that accelerated approval was designed for circumstances such as those posed by eteplirsen.
“For a disease like Duchenne muscular dystrophy and other diseases that are highly debilitating and almost certainly fatal, we hope you will employ these flexibilities and considerations for the maximum benefit of patients who have no other alternative,” wrote Ron Johnson, a Wisconsin Republican who chairs the Senate Committee on Homeland Security and Governmental Affairs, and Dan Coats, a Republican from Indiana, in their letter to FDA commissioner Dr. Robert Califf.
The missive is only the latest such attempt to sway the agency. The same lawmakers previously wrote the FDA to urge approval. And earlier this year, more than three dozen medical experts, some with ties to Sarepta, sent a letter in which they chastised FDA staff for pooh-poohing clinical evidence that the drug works. They argued that the totality of clinical trial data provides “substantial evidence” that the medicine is effective.
But FDA medical staff has taken a dim view of the drug. At issue is whether eteplirsen can sufficiently produce higher levels of a protein called dystrophin. Without this protein, muscle fibers degenerate and voluntary movement becomes impossible. But FDA staffers questioned the validity of a 12-patient study, which was not run according to the usual standards. They also expressed doubts about whether the drug produced dystrophin and the viability of six-minute walking tests that trial participants underwent.
Nonetheless, the agency has also sent mixed signals. Janet Woodcock, who heads the FDA Center for Drug Evaluation and Research, took the unusual step of not only attending the advisory panel meeting last month, but also offering remarks. To some, she seemed to suggest that agency officials are considering more than just the scientific data that was criticized by the FDA’s own neurology division.
The agency, she said, has “flexibility and that’s where we should take the views of the (patient) community into account … It’s possible to reach different conclusions based on the data presented today … Failing to approve a drug that actually works in devastating diseases — these consequences are extreme.”
Her remarks were made before an overflow crowd that included hundreds of parents and their children, some of whom appeared in wheelchairs. In fact, only one of the dozens of people who spoke during the public session, argued against approval.
The advisory panel, which consisted of scientists and doctors who are not FDA employees, voted seven to three, with three abstentions, against recommending approval. But asked whether accelerated approval should be granted, the vote was much closer vote: seven said no and six said yes. The agency is not obligated to accept panel recommendations, but usually does so.
In their latest letter, the senators argued that the way the FDA framed the questions may have made it more difficult for some of the panel members to vote in favor of the drug. They then go on to note that the issues transcend this one drug, but can be applied to other situations where patients are clamoring for life-saving medicines and need a more flexible FDA.
“Patients are crying out for the FDA to hear them,” they wrote. “They are engaged and knowledgeable and only want the agency to do what is already within their power.”
Meanwhile, some Wall Street analysts believe the agency is unlikely to approve the Sarepta drug, although some also acknowledge that accelerated approval remains a possibility. The “FDA has gone to unprecedented lengths to give transparency into its evaluation process and actually seems to want to help the community as much as they are allowed to by their mandate,” wrote Cowen analyst Ritu Baral in a recent investor note.
The story has been corrected to state that Senator Dan Coats is from Indiana, not Iowa.