Update: On November 2, the FDA approved Dsuvia. "Looking beyond this particular drug approval, I believe that we should consider whether we should be doing more to evaluate each candidate opioid," FDA chief Scott Gottlieb said in a statement.
In an unprecedented public dispute, scientists advising the FDA can’t agree over whether to allow the strongest painkiller on the market to be sold as an under-the-tongue tablet.
The drug, sufentanil, is an opioid 500 to 1,000 times more potent than morphine, and up to 10 times more powerful than fentanyl. The FDA approved an injected form of the drug more than two decades ago for severe injuries and use in surgery.
A highly addictive drug, it has long been abused by doctors who surreptitiously took it in injections. Now, in the midst of a national opioid epidemic driven by fentanyl, the FDA must decide whether to approve a tablet version of sufentanil, marketed as Dsuvia by pharmaceutical company AcelRx of Redwood City, California. If approved, the tablets would only be available at hospitals and not sold from pharmacies.
In making its decision, the FDA will rely heavily on the recommendations of a panel of medical experts. On Oct. 12, the agency’s advisory committee on new painkillers voted 10–3 in favor of approving the tablet. But just yesterday, the head of that panel wrote a seething letter to the agency opposing the vote on the grounds that the product would be easily diverted to the black market.
“It is an extremely divertible drug and I predict that we will encounter diversion, abuse, and death within the early months of its availability on the market,” wrote anesthesiologist Raeford Brown of the University of Kentucky in the letter, which was also signed by three members of the medical watchdog group Public Citizen. “It is my observation that once the FDA approves an opioid compound, there are no safeguards.”
Brown was absent at the advisory meeting on Oct. 12, along with some other panel members. His letter harshly criticized the agency’s past lax oversight of opioids, as well as its decision to hold the vote without more drug safety experts weighing in on the Dsuvia tablet that it rejected last year largely over safety concerns.
The FDA’s approval of the painkiller OxyContin for prescription in the 1990s is widely seen as the starting gun for today’s overdose epidemic, now dominated by heroin and fentanyl deaths, with increases in fentanyl-laced cocaine deaths also increasing in recent years. Fentanyl, for decades used by prescription in cancer patients and for anesthesia, was rarely a cause of overdose deaths until the past five years, when illicit forms of the drug began flooding the black market. Brown fears the same thing will happen with the new sufentanil.
But one member of the committee who voted “yes” for the tablet, anesthesiologist Ronald Litman of Children's Hospital of Philadelphia, told BuzzFeed News that the benefits of the tablet outweigh its risks.
The tablet “will allow patients in severe pain to begin to experience pain relief when they don’t yet have intravenous access,” he said by email. “It may be potentially useful in the emergency room setting or for our soldiers on the battlefield.”
AcelRx’s chief medical officer, Pamela Palmer, told BuzzFeed News that although sufentanil is a more potent opioid than fentanyl, the 30 microgram dose of the tablet delivers less of an opioid effect than the bigger doses in other painkillers do. The benefit of the tablet, packaged individually instead of in a bottle of pills, is that it delivers pain relief quickly, without an injection.
“I don’t think other people would want it — it won’t deliver the effect that illicit drug users want in such a very low dose,” Palmer said. Because of the low dosage, the company found that the drug worked without dangerous side effects even on elderly cancer patients who had never taken opioids before, she noted.
What’s more, Palmer said, “the Defense Department asked us for this drug.” Morphine injections often don’t work well on people who have lost limbs, because their blood does not circulate well. And painkiller injections are difficult for severe burn victims.
Still, Sidney Wolfe of Public Citizen criticized the FDA for not including its full drug safety advisory panel to participate in the vote, given the agency’s history with opioid approvals and the ongoing overdose crisis.
“I’m sure if [Dr. Brown] had been there, the vote would have gone the other way,” Wolfe told BuzzFeed News. “He is the rare committee chair who asks hard questions and is willing to push back.”
Wolfe was also critical of clinical trial participants reporting that they had lost some of their sufentanil tablets in past experiments, pointing to how easily they could be stolen and diverted to the black market. Partly to address concerns about missing doses, AcelRx developed a gadget that lets nurses pop the tablet under the tongue of patients, ensuring that the drugs don’t get pocketed or dropped.
Although advisory panels are usually charged with evaluating the safety and effectiveness of new drugs, Litman — one of the “yes” votes — acknowledged that “one of the concerns that should enter into the overall decision is the potential for diversion and abuse. This naturally makes all decisions about opioids that are presented for approval complicated and difficult.”
An FDA decision on the tablet is expected within six months. “Although advisory committees provide recommendations to the agency, the FDA makes the final decisions,” agency press officer Michael Felberbaum told BuzzFeed News.
This story was updated with the FDA approval and statement on November 2.