SILVER SPRING, Md., Jan. 14 (UPI) -- The U.S. Food and Drug Administration issued a complete response letter to BioMarin Pharmaceutical Inc., the maker of drisapersen, branded as Kyndrisa, a drug to treat Duchenne muscular dystrophy, indicating it has not met requirements for efficacy.
The denial has drawn the ire of researchers and members of the Duchenne patient community who anxiously await the approval of drisapersen and another drug, eteplirsen, which will be the subject of an FDA committee meeting on January 22.
The letter to BioMarin follows an FDA committee meeting last year that did not recommend drisapersen for approval based at least partially on concerns that clinical trials do not effectively increase levels of the protein dystrophin, the lack of which causes the disease.
The agency has insisted on placebo-controlled trials of both drugs to establish their efficacy and safety, though researchers and patient advocates suggest proof that dystrophin is being produced as a result of the drug without significant side effects should be sufficient to start use.
"My feeling is, it can't hurt to be approved, in the sense that it's got such a safety profile, it looks like its efficacious, and it's making protein," Lou Kunkel, a researcher who worked with both BioMarin and Sarepta, the company that makes eteplirsen, told the Boston Business Journal. "That, to me, would predict it to have an effect. And it would be a travesty not to let patients have it."
Kunkel, who also was involved in the discovery of dystrophin's role in Duchenne muscular dystrophy, said his focus is on whether the drugs promote production of the protein, as opposed to overall clinical trial results. He noted the FDA was less concerned with what the drug is supposed to do, missing the point that it may be more difficult to recruit patients for clinical trials.
"Imagine, these trials are taking place for the real efficacy in the kids who are 7, 8, 9 years old. And they're in the phase of the disease where they're going to lose ambulation by 10," Kunkel said. "So imagine if you were told this is going to be a placebo-controlled trial and your child is one of the third that wasn't going to get drug. I wouldn't sign up for that trial."
In a 2014 statement on its questions about eteplirsen, the FDA said "it would be necessary to include data in its new drug application demonstrating that eteplirsen increases production of the muscle protein dystrophin," expressing concerns over measurement methods in the company's trials of the drug.
In the materials distributed during discussion on drisapersen in November, the agency expressed concerns about both the safety and efficacy of the drug based on clinical trial evidence BioMarin presented. The materials also point to the risk for side effects being justified by the results of the trials.
Kunkel said the levels of dystrophin promoted by both drugs are not that high, adding that he shared concerns with BioMarin about the toxicity of its drug. Considering the committee hearing in November on drisapersen, he said Serapta may run into at least one of the same issues at its hearing this month.
"They are in the range where you might say they would have some effect, but they questioned BioMarin about their levels," Kunkel said. "How much would they need to be correct? Can you predict that? That's a very difficult number to put out there."
BioMarin said in a press release it is reviewing the FDA's letter and would work with the agency to determine what it needs to do next, adding that ongoing trials for drisapersen would continue as it prepares the next steps for the drug's application for approval.