WASHINGTON -- Two drugs are competing for FDA approval as treatment for Duchenne muscular dystrophy (DMD), and the agency upset DMD advocates by delaying review of one of the drugs.
On Tuesday, the FDA's Peripheral and Central Nervous System Drugs Advisory Committee discussed the safety and efficacy of BioMarin's drisapersen (Kyndrisa), which is thought to slow the progression of DMD.
They had been set to discuss Sarepta's eteplirsen this week, but that review was pushed to late January, and DMD advocates were frustrated by the agency's decision.
In an Oct. 19 to director of the FDA's Center for Drug Evaluation and Research (CDER), they explained that the consequences of postponing eteplirsen's review could affect providers' prescribing habits and payer decisions.
"Families have been expressing concerns around potential approvals and the impact such decisions have on provider prescribing recommendation and the ability of providers to have adequate information on both compounds in order to recommend the most appropriate therapy for each patient," they wrote. "These families also will need to navigate a complex payer environment and are concerned about being locked into an initial drug even if another therapy becomes available."
The letter was signed by the Duchenne Alliance, Parent Project Muscular Dystrophy, The Race to Yes, and the " from the Center for Duchenne Muscular Dystrophy at the University of California Los Angeles.
The representatives of the DMD community asked Woodcock to explain the reason for delaying the review and urged her to reconsider the change. A representative of Parent Project Muscular Dystrophy told 番茄社区 that they had not received a response from Woodcock as of Tuesday.
DMD is a rare genetic disorder found only in boys, The disease causes severe deterioration of the muscles, leaving most boys too weak to walk in their teenage years. Most DMD patients live only until their mid-20s or early 30s. There is no cure for this disease.
The muscular degeneration seen in DMD is caused by an aberration in a gene that produces the protein dystrophin, without which muscles can't function.
Both of the proposed drugs proposed are exon-skipping therapies that target the genetic aberration responsible for producing dystrophin. Drisapersen forces the mechanism that produces dystrophin to skip over the aberrant portion of the gene, exon 51, and then allows a "truncated" and "partially functional" form of dystrophin to be produced, according to .
While both drug targets the most common mutation in DMD, that mutation accounts for only 13 to 15% of DMD cases. The approval of either drisapersen or eteplirsen would be a boon for other exon-skipping therapies that have been modified to treat forms of DMD with different mutations.
Some patient advocates who support eteplirsen were said they were puzzled by the FDA's decision to allow the drisapersen meeting to occur before eteplirsen's review, especially when it appeared that BioMarin did not meet the agency's request for confirmatory trials, according to .
An FDA representative would not comment to 番茄社区 on the completeness of BioMarin's application. "Under the law, that is confidential information between the FDA and the company and we are not permitted to discuss specifics or release any non-public documents," the spokesperson told 番茄社区.
In response to questions regarding why the eteplirsen review was delayed until January, the spokesperson told 番茄社区 that advisory committee meeting dates are listed as "tentative" and aren't considered final until posted in the Federal Register.
The spokesperson also wrote that the "FDA recognizes the unmet medical need in Duchenne muscular dystrophy (DMD), the devastating nature of the disease for patients and their families, and the urgency to make new treatments available."
However, the FDA's technical review of the research for drisapersen was not yielding positive results.
Drisapersen is administered to only a subset of patients with Duchenne muscular dystrophy, following a genetic test, and given via subcutaneous injection.
In briefing documents, described drisapersen's safety profile as "concerning." Regarding the effectiveness of the drug, they wrote "while there may be some evidence suggestive of efficacy of drisapersen, the evidence is inconsistent and in some cases contradictory."
Terri Ellsworth of Pittsburgh whose son Billy, 14, has DMD, watched Tuesday's proceedings and told 番茄社区, "it's a very nervous time for our community."
Billy has been taking eteplirsen since 2011, when he enrolled in a clinical trial. Eleven other boys received treatment in the same trial. Billy is still able to walk, feed himself, dress himself, activities unthinkable to many of his friends with DMD, she said.
Ellsworth commented that the review of drisapersin did not seem to be going well. Asked whether she was relieved that eteplirsen's review had been delayed, she said, "I don't know that I'm relieved. It's just 2 more months of anxiety, but maybe this delay can be seen as a watch and learn experience."