Exactly one year after the FDA turned up its nose at AcelRx’s pain drug Dsuvia, an advisory committee has voted 10-3 in favor of its approval.
Dsuvia is a drug-device combo comprising a sublingual formulation of the painkiller sufentanil and a single-dose applicator that deposits the tiny pill under the tongue. AcelRx thinks this delivery method could be useful when intravenous or intramuscular injection might not work. This could include situations in which there is not enough time to place an IV line, such as in the emergency room, or on the battlefield, said members of the Anesthetic and Analgesic Drug Products Advisory Committee on Friday.
The FDA sent AcelRx a complete response letter for Dsuvia in October 2017 after finding fault with the safety database and directions for use included in the application. The agency wanted AcelRx to collect data from at least 50 people taking the maximum dose, address dropped tablets and other usage-related errors and run a human factors study. Briefing documents released (PDF) by the agency this week said misplaced tablets and the potential for misuse, abuse and accidental exposure would be a “significant discussion point.”
Dsuvia’s NDA included data from a phase 3 placebo-controlled trial and two phase 3 open-label studies, as well as a cross reference to safety data for Zalviso, another treatment based on sublingual sufentanil that is designed for self-administration by the patient. Zalviso earned its own CRL in 2014 because of lost tablets.
Panelists’ thoughts were mixed on whether the data adequately showed Dsuvia’s efficacy in its proposed indication: “the management of moderate-to-severe acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate, in adult patients in a medically supervised setting.”
"I don’t think we have the data to answer this question,” said Steven Meisel, director of patient safety at Fairview Health Services in Minneapolis. Because the treatment was only compared with placebo, there is no way of knowing how it stacks up against other painkillers such as ibuprofen, acetaminophen, aspirin and morphine, Meisel said.
Ron Litman, an anesthesiologist at the Children’s Hospital of Philadelphia, was “not overwhelmed by the usefulness of the drug,” but believed that its “benefits outweight its risks based on the unique ability to be used sublingually.”
Other panelists said the data supported efficacy, but that they were unsure the treatment would “fit a niche.” Most hospital patients undergoing operations already have IV lines through which to receive painkillers, for example. And eliminating the IV from delivering opioids may introduce a new danger—the inability to deliver naloxone intravenously in the case a patient needs to be rescued.
Most of the panelists were in agreement on the potential misuse or abuse of Dsuvia.
“I’m not overly concerned about the abuse issues with this particular product; all opioids can be abused as this one, no doubt, will be,” Meisel said.
Meisel, along with two others, Jacqueline Willacy and Michael Fischer, voted against approving Dsuvia, while the remaining 10 panelists voted in favor of approving it. Some of those who voted in favor did so with some caveats. These included specific labeling language about where it should be used—in military or emergency situations—and the age of patients in which it should be used. More than one panelist flagged the weakness of safety data in elderly patients.
The FDA is expected to make a decision on Dsuvia by Nov. 3.