‘I don’t want any more Kentuckians to die’; UK doctor leads charge against new opioid pill 

A University of Kentucky doctor is leading the charge against FDA approval of an opioid pill that’s 10 times stronger than fentanyl, a drug blamed in more than 30,000 overdose deaths in the United States last year.

Raeford Brown, M.D., a professor of anesthesiology and pediatrics at UK, chairs the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee committee that on Oct. 12 approved DSUVIA, a pill form of sufentanil, a synthetic opioid that is used for IV and epidural anesthesia. The pill would dissolve under the tongue. The committee vote was scheduled despite the fact that Brown and several other members had told the FDA they would be unable to attend because of the American Society of Anesthesiologists meeting being held in San Francisco at the same time.

“I informed the FDA that I would not be at this meeting, and they made the decision to have the meeting without me,” Brown said in a telephone interview Tuesday. “And because this is such a problematic formulation of a potent opioid, I felt that I should make known my concerns and so I did.”

Brown wrote a letter with several researchers from the Public Citizen’s Health Research Group to outline their opposition to the approval. Brown said that as a doctor in Kentucky, he’s at ground zero of the opioid epidemic, and it’s obvious that a drug like DSUVIA could be easily diverted from hospitals and make the crisis even worse.

According to the National Institute on Drug Abuse, of the more than 70,000 overdose deaths last year, 30,000 were due to fentanyl, which has been counterfeited in China and Mexico in recent years. In Kentucky, 1,565 people died in overdose deaths and 52 percent were ascribed to fentanyl.

“My main concerns is that we still have an opioid crisis, we still have an acute death rate and, we’re still writing 200 million opioid scrips per year, prescriptions are still being diverted and we have yet to find a way to prevent that,” Brown said.

Brown says he doesn’t know why the FDA held a vote without him and other pain experts. The FDA did not respond to a request for comment.

The FDA is expected to make a final approval on Friday.

DSUVIA is being developed and marketed by the company AcelRX Pharmaceuticals, which in 2015 signed a contract with the U.S. Army for $17 million to develop a drug for battlefield use. Soldiers with devastating injuries go into shock and require multiple morphine injections, which can lead to death; AcelRx officials have said in interviews that DSUVIA requires less blood flow to deliver pain relief. They have also said that because of its one pill format and its availability only in hospitals, the danger of diversion is much less.

But according to clinical trials, DSUVIA would deliver “meaningful pain relief” after 58 minutes, which is too long, said Sidney Wolfe, co-founder of the Public Citizen’s Health Research Group and a cosigner of the letter to the FDA.

“The other thing that the studies failed to do was check out other existing approved methods of treating pain, including other opioids that aren’t as dangerous as this one,” Wolfe said.

Wolfe said it’s also strange that the advisory committee met to approve an opioid without the input of the Drug Safety and Risk Management Advisory Committee. Usually, opioid approval would require that both committees vote. 

As for diversion, the letter states, sufentanil has been most diverted by health workers in hospitals, even though it is currently only available in liquid form.

“It (sufentanil) is so potent that abusers of this intravenous formulation often die when they inject the first dose; I have witnessed this in resuscitating physicians, medical students, technicians, and other health care providers, some successfully, as a part of my duties as a clinician in a major academic medical center,” Brown wrote. “Because it is so potent, the dosing volume, whether in the IV formulation or the sublingual form, can be quite small. It is thus 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.”

Pamela Palmer is the chief medical officer and co-founder of Acel Rx and herself a former practicing anesthesiologist. She said she designed DSUVIA as a way to counteract medication errors with IV morphine, which happen because liquid morphine comes in so many concentrations. U.S. Army personnel heard one of her presentations and asked her to develop it for battlefield use. Each DSUVIA pill is 30 micrograms, administered with a syringe-like device that places the pill under the tongue, so it’s impossible to make a dosing error, she said.

In addition, Palmer said, opioids diverted from hospitals make up a tiny percentage of the total opioid diversion, such as when people sell their prescription pills. “So we will have checks and balances to make sure this is only shipped to and used in medically supervised settings,” she said. “By keeping it there, we’ve addressed 99 percent of abuse and diversion.”

Palmer said patients or soldiers with severe trauma may have limited blood flow, which keeps IV morphine from kicking in. Sufentanil is much more lipophilic than morphine, meaning it rushes to fatty membranes, of which there are many under the tongue.

“So sufentanil can get to your blood and brain faster than morphine,” she said. She said initial pain relief begins in 15 minutes and “meaningful” relief is at about 50 minutes.

On Wednesday, Avisol Capital Partners issued a release saying the newsletter endorsed AcelRx’s prediction of $1 billion in peak revenue from DSUVIA by 2027, although it said that the drug’s approval may be in jeopardy because of Brown and others. “The company may also be required to boost its marketing efforts to counter this negative publicity, impacting its cash flows marginally,” the newsletter said.

The introduction of prescription opioids such as OxyContin is widely believed to have started the current opioid crisis because it was overprescribed in the erroneous belief that the time-release format would not be addictive. Brown believes that diversion from medical settings is still a serious problem. 

“We’ve had thousands of Kentuckians die because of fentanyl and other opioids, and I’m really attached to this because I don’t want any more Kentuckians to die,” he said. “It just seems to me that having more opioids on the market is likely going to not be helpful for us in protecting our fellow citizens. I’m trying to protect people from the folks that don’t have the big picture.”

Van Ingram, the head of Kentucky’s Office for Drug Policy, said he was concerned that another form of a dangerous opioid was being introduced. 

“If there’s a way it can fall into the wrong hands, it will,” he said.

Last year, he noted, the FDA requested and received the withdrawal of Opana, a long-lasting opioid manufactured by Endo Pharmaceuticals after the FDA noted that the harm it caused outweighed the good.

Wolfe says the FDA should be making the same determination about DSUVIA before it can cause harm.

“This drug is likely to get approved, if it gets approved, it will kill people,” Wolfe said. “It’s just a matter of does the FDA know enough to pay attention to all the evidence? Do they have enough courage and concern for public health? It will come off the market but only after a sufficient number of people die.”

By Linda Blackford
Lexington Herald-Leader