Below are four points that appear to me to be significant errors, and that are easily explainable:
1. The FDA’s choice of a the control group is arguably flawed. The company, in its rebuttal on Friday, said that the control patients chosen by the FDA (from the GlaxoSmithKline trial) contained kids under 7 years old, and those who could walk a farther distace at the outset than any in its own trial. Those factors would naturally raise the average performance of patients in the control group, diminishing the difference between them and the boys receiving eteplirsen.
2. Even accepting the comparison, compared to the 12 boys in Sarepta’s trial, those in the GlaxoSmithKline trial lost the ability to walk at a significantly faster rate. Two of the 12 boys in Sarepta’s trial are now restricted to wheelchairs after four years. That’s 17 percent. By contrast, according to data shared by GSK at the World Muscle Society presentation in October 2013, about 20 percent of boys older than 7 lost their ability to walk after just one year. At that rate, more than half (about 59 percent) would have been unable to walk after four years.
3. The FDA’s argument that boys in Sarepta’s trial received more steroids than the boys used for its control group appears wrong. Jenn McNary, a mother of a boy in the trial, already made this argument last Friday, saying her son was underdosed with steroids during the course of the trial. But there’s evidence in Sarepta’s application itself to support this (specifically, in Appendix 3). The actual baseline doses of steroids are listed (some are in milligrams, while others are in milligrams per kilogram). Converting them all to milligrams per kilogram, and averaging each arm, the boys in Sarepta’s trial received an average baseline dose of 0.79, less than the average of boys in the control group of 0.81.
Some industry analysts say the FDA may still approve the Sarepta drug, despite the staff’s misgivings, if the advisory committee concludes it is safe and offers some benefits to patients. Many patients and their families, who had been disappointed by the ruling on BioMarin’s drug and the briefing document, are expected to testify before the advisory panel.
More from the Globe:
Hopes for a speedy approval were dashed last week, however. First the FDA rejected BioMarin’s experimental drug, drisapersen, saying the company would have to conduct additional studies to prove its effectiveness. Then the agency’s briefing document on Sarepta’s eteplirsen pointed to a number of inconsistences in the data generated to show clinical benefits in a company trial involving a dozen patients.
Sarepta responded with its own detailed point-by-point rebuttal and called for flexibility in evaluating drugs for unmet needs of small patient populations. “The need for innovative and flexible approaches to FDA review... increases as more rare disease therapies are being developed where the contextual knowledge of patients and their diseases often evolves in parallel with clinical development,” the company wrote in its rebuttal.
"Sarepta and a group of advocates for Duchenne therapies will use the delay to hone their presentations to the advisory panel, including the company’s rebuttal of a briefing document issued by the FDA staff last week. The staffers on Jan. 15 questioned the methodology of Sarepta’s research and the benefits of its drug candidate, eteplirsen, in a small clinical study, news that sent the company’s stock down by more than half.
“We’re optimistic that the data will show that his will be a safe and effective treatment for muscular dystrophy patients,” said Dr. Laura Hagerty, scientific program officer for the Muscular Dystrophy Association, who had been scheduled to address the advisory committee Friday. “We know it’s the FDA’s job to do the review. We encourage them to keep our families in the forefront of their minds, and to get therapies in the hands of patients as soon as possible.”