In 2016, Cambridge biotech Sarepta Therapeutics won approval for the first treatment of Duchenne muscular dystrophy after families of boys with the deadly muscle-wasting disease urged the government to overrule a panel’s finding that questioned whether the drug worked.
Now, a nonprofit Boston-based drug-cost watchdog has issued its first-ever review of Duchenne drugs, including that medicine and a second experimental one for which Sarepta is seeking approval. The report is preliminary and highly technical, but its conclusion is withering: Evidence that the two medicines work is so scant that the watchdog can’t even say how much they should cost.
“The underlying evidence for evaluating the cost-effectiveness of treatments in DMD remains sparse,’’ says the draft report released late Wednesday by the Institute for Clinical and Economic Review, or ICER. When it comes to Exondys 51, the controversial drug approved in 2016, said the report, “There is no high- or moderate-quality evidence demonstrating improvements in function.”
Exondys 51 has a yearly price tag of about $300,000, based on the patient’s body weight.
As for the second drug that Sarepta hopes to get a go-ahead for later this year, now known as golodirsen, the watchdog group said evidence of its effectiveness is “even more limited.”
ICER, whose influence has risen as drug prices have skyrocketed, may revise its findings based on public feedback before issuing a final report on July 11. But the draft document drew a swift rebuke from Sarepta on Thursday.
In a statement, the drug maker called ICER’s approach “fatally flawed,” although Sarepta didn’t address how effective Exondys 51 and golodirsen are.
“ICER’s model is unfit to evaluate rare disease populations in a manner that would encourage innovation to bring profound treatments to patients living with, and far too often dying from, rare disease,” the company said.
As a result, Sarepta said, it will not participate in the ICER review process “until it adapts its model to address the inherent limitations and biases.”
Exondys 51 generated more than $300 million in sales last year, according to Sarepta.
Duchenne is a rare fatal neuromuscular disease caused by mutations in the dystrophin gene that result in a progressive loss of muscle function and weakness, including in the heart and skeleton. The disorder strikes about 1 in 3,500 to 5,000 boys, who typically lose the ability to walk by age 12 and don’t live past 25. Girls can carry the mutation but are rarely symptomatic.
Sarepta, which specializes in developing drugs for rare diseases, sought approval for Exondys 51 in 2016, saying that the medicine produced more dystrophin in patients.
But an FDA advisory panel of medical scientists concluded in a 7-6 vote that Sarepta’s clinical study failed to meet the standard for accelerated approval. In a separate 7-3 vote, with three members abstaining, the committee determined that Sarepta’s clinical trial was poorly designed and didn’t prove the drug was effective.
Sarepta’s trial involved just 12 patients and didn’t include any patients taking a placebo. Trials for treatments of more common diseases often enroll hundreds of patients, with some given a drug and others a placebo so the two groups can be compared.
Usually, such votes by an FDA advisory panel are fatal. But five months later, the FDA overruled the committee and its own staff and approved Exondys 51, a move described by some stock analysts as almost unprecedented.
The approval required Sarepta to conduct a study to confirm that its treatment can improve motor function in Duchenne patients losing the ability to stand and walk. A Sarepta spokeswoman said Thursday that the study is continuing and that the company has gathered evidence that Exondys 51 slows the progression of the disease.
Advocates for Duchenne patients have argued for a new standard in considering proposed drugs for rare genetic disorders with no other treatments. They said the FDA should not require the same level of data generated in large-scale clinical trials for more common diseases.
The new ICER study also scrutinized the effectiveness of a third medicine, Emflaza, which was approved in 2017 and marketed by Illinois-based Marathon Pharmaceuticals.
Emflaza works differently than Exondys 51 and golodirsen. It a corticosteroid, a class of anti-inflammatory drugs commonly used around the world to treat Duchenne. Emflaza initially had an annual price tag of about $89,000 a patient. That was later reduced to about $65,000.
ICER said Emflaza provided some benefits, but that it is still overpriced.
Jonathan Saltzman can be reached at firstname.lastname@example.org.