In regard to the upcoming RETT trial as well as A2-73's safety record and preliminary efficacy results, it might be useful to review the events leading up to last September's FDA approval of Sarepta's Duchenne muscular dystrophy drug, eteplirsen. Most of this information comes from an article written by Ed Silverman, a senior writer for Pharmalot, who covers the pharmaceutical industry.
The approval of this drug was very contentious. The decision came after months of debate about whether Sarepta had provided enough evidence to demonstrate that eteplirsen had a meaningful impact on patients. "A key issue was whether the drug can sufficiently produce higher levels of a protein called dystrophin. Without this protein, muscle fibers degenerate and voluntary movement becomes impossible. The FDA also raised doubts about the results of a small, 12-patient clinical trial that Sarepta relied on to make its case....Moreover, the company failed to conduct a larger trial involving the use of a placebo, as the FDA had requested. In light of these concerns, an FDA advisory panel in April (2016) voted that the drug not be approved and, by a narrow margin, also agreed that the drug does not appear to be effective. Those decisions were made at a day-long meeting that was punctuated by a parade of emotional pleas from parents and children, some of whom appeared in wheelchairs. Despite the outcome, the agency appeared to signal that parents should not lose hope. In remarks designed to appease the crowd, Janet Woodcock, who heads the agency division that approves drugs, said that "It's possible to reach different conclusions based on the data presented today...Failing to approve a drug that actually works in devastating diseases--these consequences are extreme." And so, the FDA made an unexpected request for Sarepta to provide more data about muscle biopsies from 13 boys who participated in the ongoing trial in order to determine the extent to which the medicine may produce dystrophin. THE MOVE SUGGESTED THAT THE FDA TRIED TO FIND OTHER WAYS TO APPROVE THE DRUG."
Five months later, in September, 2016, the FDA approved the drug. "In reaching its decision, the agency essentially overruled its own medical staffers, who earlier in the year questioned the effectiveness of the drug, which was tested in a small clinical trial. The wrangling raised still larger questions about standards for approving a drug, especially when it's intended for patients with a rare and deadly disease and no other treatment options." "In rare diseases, new drug development is especially challenging due to the small numbers of people affected by each disease and the lack of medical understanding of many disorders," said Dr. Janet Woodcock. As a condition of the approval, Sarepta will have to conduct a two-year randomized control trial to verify the clinical benefit of the drug.
The approval delighted a frazzled, but vociferous community of parents, whose determined lobbying efforts were reminiscent of the movement three decades ago to force regulators to green light AIDS treatments."
"The fate of the Sarepta drug has been closely watched as a litmus test for an intensifying struggle between the FDA and patient groups that want the agency to take a more expansive view toward approving medicines for unmet medical needs. In this instance, patient advocates hoped the FDA would use the accelerated approval process to endorse eteplirsen. This approach relies on a substitute outcome in a clinical trial to suggest a drug may have, but does not guarantee, a benefit."
Subsequent to all of this, as we all know, the Twenty First Century Cures Act has been passed. Part of the drug approval process under this act is the patient's and caregiver's perspectives on how the patient is responding to the medicine. The FDA stated that "Real world evidence and the stronger inclusion of patient perspectives on endpoints are two examples of the shifts that will impact therapy development." In this regard it seems significant that RETT parents are extremely involved and, in regard to A2-73, all patients wanted to continue the medicine after the end of the trial. Also the Australian media exposure supports very strong patient and caregiver responses. Additionally, in regard to potential accelerated approval and substitute outcomes, the impressive EEG/P300 results could qualify for that as, according to MacFarlane, "these are the kinds of studies that got donexepil approved by the FDA." Moreover, a positive outcome from Biogen's remyelination tests on A2-73 might also qualify, particularly in the context of A2-73's safety record.
News 
Market Data 
Discover 
AI
