Snowstorm Dashes Hopes for Sarepta Drug's Dystrophy Patients

  • FDA hearing on controversial drug delayed by bad weather
  • `Devastating,' says father who traveled to D.C. with sick son

Dozens of doctors and families who flew to Washington with sick children to try to convince regulators to approve Sarepta Therapeutics Inc.’s experimental drug for a deadly disease are left at loose ends, their hopes on hold after a review was delayed due to the approaching snowstorm.

For some parents who traveled with sons affected by Duchenne muscular dystrophy, it was too late to cancel flights after the hearing slated for Friday on the drug, eteplirsen, was postponed by the U.S. Food and Drug Administration on Wednesday.

The storm, which threatens to drop more than than 2 feet (61 centimeters) of snow on D.C., is the third setback in a week for a community awaiting the first treatment for a progressive disease that causes muscles to waste away in as many as 3,500 American boys and young men -- killing most patients by age 25. The FDA staff said Jan. 15 that the Sarepta product hasn’t been proven to work in clinical trials, a day after the agency rejected a competing drug, BioMarin Pharmaceutical Inc.’s Kyndrisa. Sarepta could still get approval, but the prospects look dimmer.

Stan Nelson and Carrie Miceli had came all the way from Los Angeles, where they co-direct the Center for Duchenne Muscular Dystrophy at the University of California, which covered their travel costs. They also brought their 14-year-old son Dylan, who has the disease and is in a wheelchair. While it’s increasingly difficult for Dylan to travel, Miceli said they wanted him to be present for what could be a historic time in drug development.

“It’s devastating, to be honest,” Nelson said Wednesday by phone outside of the Sheraton hotel in Silver Spring, Maryland. Nelson estimated that about a hundred patrons, including scientists he met from Australia and the U.K., traveled like him for a meeting of the FDA advisory committee that won’t take place.

When the FDA reviews a drug, especially one where the evidence of effectiveness is in question, and even more so when the disease is deadly, patient activists can become a loud voice asking for approval. They can also become a center of debate, because patient advocacy groups are sometimes funded by the industry.

‘Take the Risk’

The families and Sarepta, whose stock has plummeted 68 percent this year, may yet have a chance to convince the FDA to clear the drug when the hearing is rescheduled. The company is seeking what’s called an accelerated approval. The program is designed to speed drugs to market for rare and undertreated diseases based on preliminary data, with definitive studies confirming any benefit to follow -- which could help Sarepta’s case. BioMarin, by contrast, had sought full approval for its Kyndrisa treatment.

“Ideally you would like to see more data, but you are facing the reality of an underserved patient population that doesn’t have a meaningful treatment,” said Peter Karachunski, a pediatric neurologist at the University of Minnesota Medical Center. “From a biological standpoint, it’s very promising. Sometimes you have to take the risk and approve something that’s not 100 percent sure, knowing that a clinical trial where we have a greater number of patients is underway.”

In their report last week ahead of the hearing, FDA staff pointed to some biologic activity, even though it concluded that the effects of Serapta’s eteplirsen on patients were too small and variable. The central defects that lead to the genetic condition are marked by the complete absence of dystrophin, an essential protein needed for healthy muscle. FDA staff members found that eteplirsen increased dystrophin levels about three-fold compared to the trace levels typically detected in children with Duchenne. They still had less than 1 percent of normal levels after 180 weeks of treatment. While that’s a paltry amount, it’s a leg up on BioMarin, which was unable to prove Kyndrisa boosted production of the protein at all.

Sarepta, responding to the report, pointed out that boys treated with its drug were able to walk more than 100 meters (328 feet) further in six minutes than an untreated group. While two boys given the drug worsened almost immediately and were unable to walk by their 10th birthdays, the remaining 10 were still ambulatory four years later, including four aged 14 and older.

‘We Were Stunned’

Most boys with the disease start to lose their ability to walk and become wheelchair-bound early in their teenage years. Only one of the 10 boys in the comparison group was able to walk after four years. The FDA staff members dismissed the findings, pointing out that there could have been bias in forming the comparison group and saying there were no significant differences in walking distances between the two groups when all the patients were considered.

Terri Ellsworth and her 15-year-old son Billy, who were planning to bring buttons to the advisory committee hearing with the caption: “A little dystrophin is better than no dystrophin,” never made it to D.C. The pair were at the airport gate in Pittsburgh, where they live, when they got the news about the delay.

“We were stunned,” said Ellsworth, who credits the drug for the fact that Billy is still walking today. “Sarepta had its hands smacked so many times,” she said. “It’s like, ‘Here we go again.’”

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