The FDA’s Analgesic and Anesthetic Drug Advisory Committee (AADPAC), of which I am a member, met October 12 to discuss a controversial New Drug Application (NDA) for a powerful opioid called sufentanil, manufactured by AcelRx.
Like fentanyl, sufentanil is a short-acting synthetic opioid, but approximately 5 to 10 times more potent. In the midst of the current opioid crisis, why would anyone think that the availability of another powerful opioid is a good idea?
Because unlike previous formulations of sufentanil, which are administered intravenously (IV) primarily by anesthesiologists, this proposed formulation, named Dsuvia, is designed to be administered sublingually, as a tablet that dissolves under the tongue.
Dsuvia would be used only in highly-monitored acute-care settings, and will be especially useful for patients without IV access. For example, the Department of Defense has taken an interest in this unique formulation for administration to injured soldiers on the battlefield prior to obtaining IV access.
Advisory committees, which are made up of experts in their respective fields, help the FDA evaluate scientific studies of efficacy and safety that are required with each sponsor’s NDA submission. Advisory committee meetings consist of a series of presentations, first from the pharmaceutical sponsor, then the FDA scientists, and finally members of the public who present their viewpoints (some public speakers who encourage the committee to vote for approval have had their travel expenses paid for by the sponsor).
The panel of experts then has the opportunity to ask clarifying questions of the sponsor and the FDA, and each expert is invited to voice their opinion using a series of prompts suggested by the FDA, prior to a final vote to approve the drug. The discussion of whether or not to approve a new opioid formulation is uniquely complicated because besides the regulatory criteria of efficacy and safety that are normally required to approve a drug for public release, opioid experts must take into consideration the drug’s potential to cause addiction and abuse.
At the October 12 meeting, we voted to approve Dsuvia by a margin of 10-3 (I was one of the “yes” votes). Although the FDA is not bound by the outcome of the committee’s vote, during its deliberations, the FDA staff review the transcripts of the discussion and in most cases their final decision mirrors the vote.
Six days after our meeting, the non-profit medical watchdog group Public Citizen sent a letter to FDA leadership criticizing the outcome of the vote and urging the FDA to reject AcelRx’s NDA for Dsuvia. But, in a bizarre twist, the letter was co-signed by Dr. Raeford Brown, the Chair of the AADPAC, who because of other commitments, was not able to attend the meeting in person.
Dr. Brown and Public Citizen asserted that Dsuvia is too dangerous for public release, and in an interview Dr. Wolfe stated that had Dr. Brown been present at the meeting, he would have influenced the vote in the opposite direction.
The letter attracted media coverage, as well as an admonition by Senator Edward J. Markey (D-Mass) urging the FDA to reject the submission.
This controversy is emblematic of several broader questions that arise when considering the approval of a new opioid: Is it enough to approve the opioid if it merely works better than placebo, as long as the risk-benefit ratio is favorable? Or in light of the present opioid crisis, should any new drug have significant advantages over the opioids already in use? Furthermore, what criteria should be used by the AADPAC and the FDA to gauge the potential for addiction and abuse? Unsurprisingly, opioid experts have widely differing answers to these questions.
This week, the FDA announced its approval of AcelRx’s NDA for Dsuvia. The approval was accompanied by a lengthy explanation and defense of the approval by FDA Commissioner Dr. Scott Gottleib.
In his statement, Gottleib said he has asked the FDA “to evaluate a new framework for opioid analgesic approvals; one that provides a transparent process to delineate clearly, eventually in new guidance, how we intend to consider the benefits and risks of these products in the context of this crisis.”
Ron Litman, D.O., M.L. is a pediatric anesthesiologist at the Children’s Hospital of Philadelphia and a member of the faculty at UPenn medical school. He is the medical director of the Institute for Safe Medication Practices, the largest non-profit dedicated to medication safety in the world. Last year he joined the FDA’s AADPAC.
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