FDA Panel OKs Stronger Opioid Despite Concerns

Oct. 18, 2018 -- An FDA panel this week gave preliminary approval to a new kind of opioid for pain that is five to 10 times more potent than fentanyl. The drug advisory committee voted 10-3 to approve the drug, sufentanil, which would be marketed as Dsuvia. The panel vote is not the final step of approval, but the FDA regularly follows the committee’s lead.

"We are pleased with the advisory committee's recommendation to approve Dsuvia as a treatment in medically supervised settings for adults experiencing moderate-to-severe acute pain," Pamela Palmer, MD, PhD, chief medical officer and co-founder of manufacturer AcelRx, says in a news release.

"We believe Dsuvia represents an important noninvasive acute pain management option with potential to significantly improve the current standard of care."

But at least one committee member feels quite differently.

Raeford E. Brown Jr., MD, a professor of anesthesiology and pediatrics at the University of Kentucky, who chairs the committee, says he is concerned about allowing an opioid as potent and potentially lethal as this one onto the market. He's also worried about the lack of appropriate education for doctors who might prescribe it.

"The FDA's inability to enforce controls, the potency of the drug, and the ease with which it will be diverted are some of the reasons why I would never consider this product for marketing in the U.S.," says Brown, who was unable to attend he committee’s meeting.

Sufentanil is a synthetic opioid that is used for IV and epidural anesthesia. It is a pill that dissolves under the tongue.

The new sufentanil formulation was designed for rapid pain relief. It can take effect in as little as 15 minutes and can last for about 3 hours.

AcelRx says the drug’s single-dose, prefilled, disposable packaging should prevent dosing errors and misuse.

The company says there's a need for opioid pain medicines that don't require swallowing, because some patients have difficulty taking oral medication and may not have access to IV opioids.

The FDA had earlier flagged two safety concerns. These include possible adverse effects in patients who require the maximum proposed dosing, and the risk for misplaced pills (they're small in size), which could contribute to abuse and accidental exposure. The company had submitted a new drug application for consideration.

To address the first concern, the company lowered the maximum daily dose from 24 to 12 tablets and provided new safety data. To address the second concern, the company modified directions for use and carried out another study.

The new results showed that although the rate of opioid-related gastrointestinal adverse effects were generally higher in patients who took the maximum daily dose, the rate of other adverse effects were comparable between higher- and lower-dose groups.

The company emphasized that the product is not intended for home use and would only be available in doctor’s offices or in hospitals. It would not be sold at drugstores even with a prescription.

"The availability of a single-dose, noninvasive opioid, like Dsuvia, could significantly improve my ability to effectively, efficiently and safely alleviate acute pain experienced by my patients," David Leiman, MD, a clinical assistant professor of surgery at the University of Texas at Houston, says in the company news release.

Diversion, Abuse, Death

In Brown's view, though, sufentanil poses substantial risks for respiratory failure, abuse, and death.

Right now, the drug is restricted to IV use by professionals such as anesthesiologists who have some understanding of its dangers, he says. "It's really a drug used in the operating room where there are airway management experts available."

But outside that environment, doctors across the United States have little experience with this drug, Brown says.

Sufentanil is "extremely divertible," he says. "We have learned a hard lesson in the US that if you put a drug on the market, it will be diverted, and if it's diverted, people will die."

The drug is so potent that people "will become rapidly addicted to it" and may be in danger of overdosing or "rapidly transitioning" to heroin if it's not available, Brown says.

For the drug to be restricted to closely controlled settings, prescriber education needs to be guaranteed, something that Brown says is not the case. All too often, he has seen the same scenario "pan out" with other opioids over the years.

"There's the suggestion that a drug will be fine because it will be closely monitored, and then it's not. The FDA realistically does not have the statutory authority, or the will, to go after people who are using these drugs inappropriately," he says.

Brown has let his views be known to the FDA. He says he "begged" the agency not to hold the advisory committee meeting while anesthesiologist members like himself were unavailable (they were attending the American Society of Anesthesiologists in San Francisco), but the meeting went ahead anyway.

He's convinced that had he attended, the discussion would have been different, as would the vote.

He sees himself as the "voice of reason" concerning public health and does not feel it's his role to "protect the profit margin" of the pharmaceutical industry.

Brown wasn't the only one with concerns. Meena Aladdin, PhD, a health researcher with Public Citizen's Health Research Group, was scheduled to testify against approving sufentanil before the FDA panel.

The drug "does not offer any unique advantages over the numerous available FDA-approved opioid products for treating acute pain, and thus does not fill any unmet medical need," Aladdin says in a news release from Public Citizen. "However, it does pose unique risks of serious harm if it's misused or abused or if accidental exposure occurs."