The FBI called a powerful opioid developed for the military a public threat. The company selling the drug says it'll save lives.

In October 2018, Dr. Raeford Brown was attending a meeting of the American Society of Anesthesiologists in San Francisco when, back in Washington, the Food and Drug Administration advisory committee he headed met to review Dsuvia, a powerful new opioid.

Brown had long believed that the drug agency had scheduled the critical vote specifically for a date when he couldn’t attend. He had asked the FDA to move the meeting, and agency officials had refused, he later recalled.

A few weeks later he was working from his home office in Lexington, Ky., when Dr. Janet Woodcock, director of the Center for Drug Evaluation and Research at the FDA, called to tell him that Dsuvia had just been officially approved.

“I told her that I thought that was a bad decision,” Brown, an anesthesiology professor and clinician at the University of Kentucky, said in a recent interview. “I told her exactly why.”

Brown, who until recently headed the FDA’s advisory committee on analgesics and anesthetic drug products, was upset. In his absence, the committee had voted 10-3 to recommend approving Dsuvia, which likely influenced the FDA’s final decision.

Woodcock, according to Brown, said there had been pressure from the Pentagon to approve the drug, which the military had paid to help develop. “It was her trying to get me to shut up,” he said.

Dsuvia, which is delivered as a pill that is smaller than a Tic Tac, is a close chemical relative of fentanyl. A Drug Enforcement Administration scientist recently testified that it is 1,000 times stronger than morphine. Brown’s opposition to Dsuvia was based on the belief that approving this new drug, amid a nationwide opioid epidemic, would lead to more addictions and deaths.

It turns out he was not alone in his concerns.

Just six months later, in May 2019, the FBI, in an intelligence bulletin marked “for official use only,” warned that this new painkilling drug would likely exacerbate the nation’s opioid crisis.

The FBI warning about Dsuvia was dire. “Because of its potency, Dsuvia likely will cause deaths at a rate surpassing that associated with fentanyl, increasing the overall opioid-related death rate in the near term,” said the bulletin, which was obtained by Yahoo News and has not previously been made public.

Members of Congress, patient safety experts and public health advocates share the FBI’s worry and say that with several hundred opioids already on the market there is no need for another one. The drug’s critics point out that Dsuvia may be particularly dangerous because it is available only in a single dosage, and therefore can’t be adjusted for a given patient’s weight or overall health. They are outraged that the FDA would approve a highly potent new opioid at a time when a nationwide epidemic is raging.

About 68,000 Americans died of drug overdoses in 2018, according to the Centers for Disease Control and Prevention — slightly fewer than in 2017, but still tens of thousands more than died annually from AIDS at the height of that epidemic.

Dsuvia’s development and approval are in large part the result of interest from the Department of Defense, which had invested in the drug to help wounded soldiers and, last month, finally cleared it for use in military kits. But a number of people connected to the military medical community say they fear Dsuvia may be unsafe without more understanding of how to dose it, and believe the Defense Department will never end up using it widely.

Advocates of Dsuvia say that it addresses a military need, and that particularly now, with the coronavirus pandemic driving shortages in some drugs, it could fill a significant niche in hospitals and prevent possible accidental overdoses using liquid opioids. And patient advocates say the opioid crisis has led to hysteria that threatens access to medication for the estimated 50 million Americans living with chronic pain and the 20 million afflicted with severe chronic pain. “All opioids are not bad,” says Kelly Dineen, who worked as an intensive care and neurology nurse for 11 years and is now a health policy law professor at Nebraska’s Creighton University. “Prescription opioids can be and are an effective tool.”

Dsuvia placebo. (Sam Matthews/Yahoo News)
Dsuvia placebo. (Sam Matthews/Yahoo News)

The controversy over Dsuvia, a synthetic opioid, illustrates the competing pressures of a country whose attention has turned from an opioid epidemic to a coronavirus pandemic in the course of just a few months. The government spent several years trying to crack down on painkiller abuse and limit production, and now hospitals are seeing shortages of some opioids needed to intubate patients. Even with those shortages in hospitals, the opioid epidemic continues to kill tens of thousands of Americans every year. While the most recent CDC statistics available suggest opioid overdose deaths are in decline overall, death rates involving synthetic opioids increased by 10 percent from 2017 to 2018.

The company behind Dsuvia argues that it spent years developing a better drug that will save lives by reducing frequent mistakes made with injectable opioids. Critics say that neither the Pentagon nor the drug’s manufacturer has laid out a convincing need for a new opioid, particularly one as powerful as Dsuvia, and that profit, not pain management, is behind the push. And the FDA, which focuses on a drug’s safety and effectiveness, not its need, is caught in the middle.

The Pentagon’s interest in a better painkiller dates back to the early days of the Iraqi insurgency, when U.S. troops were being injured or killed in increasing numbers by roadside bombs. In 2003, Chester “Trip” Buckenmaier III, a specialist in acute pain management and now a key advocate of the military’s use of Dsuvia, traveled to Iraq to help treat some of the early victims of these crude bombs. Injuries from what are called improvised explosive devices were gruesome: severed limbs, horrific burns and bodies torn apart by shrapnel.

But battlefield treatment for soldiers with traumatic injuries hadn’t changed much since the Civil War — they were given morphine injections, which often weren’t effective at blocking the pain.

“When I arrived in Iraq, three months after we had gone over in 2003, that was the only drug we had for pain at the time, and it was not optimal for the environment that we were working in then,” recalled Buckenmaier, a retired colonel who is now director of the pain clinic at Walter Reed National Military Medical Center, in an interview with Yahoo News. “And so the need was clearly defined. That was obvious to everybody.”

Around the same time, aware of the need for better painkillers, military medical experts decided to try out fentanyl lollipops, which were then used to treat intense pain in cancer patients. Sugary lozenges containing the powerful painkiller fentanyl, the lollipops were given to 22 injured soldiers fighting in Iraq and were found to be very effective battlefield pain relievers.

The following year, the Pentagon’s Committee on Tactical Combat Casualty Care, which sets guidelines for battlefield medicine for the entire military, recommended the use of fentanyl lollipops “off label” — meaning that while they were not specifically approved for battlefield use, they could be administered there. The lollipops were portable and easy to make use of in a combat environment. They were also better at relieving pain than the morphine shots the Pentagon had largely relied on previously. But the dosing was imprecise, so Buckenmaier was still looking for better solutions.

Package and example of fentanyl lollipop (brand: Actiq), 400 micrograms. (Photo: Crohnie via Wikicommons)
Package and example of fentanyl lollipop. (Crohnie via Wikicommons)

As the military researched options for pain management on the battlefield, back in the United States, Pamela Palmer, then the medical director of the Pain Management Center at the University of California, San Francisco, was getting calls from malpractice lawyers about an entirely different problem with painkillers. Hospitals were seeing a large number of accidental overdoses due to frequent mistakes dosing injectable opioids.

The answer, she thought, might be a drug called sufentanil, which could be delivered in pill form and thus, Palmer said, would not be as likely to trigger an accidental overdose. “Everyone would take a pill if they could,” she said, “if it worked as well and as quickly.”

Excited by the prospect of being an entrepreneur, she founded her own company, AcelRx, with plans to develop and market sufentanil-based products to hospitals. For Palmer, starting her own company meant leaving a tenured university position, but Silicon Valley’s booming biotech sector beckoned.

In 2009, Palmer’s quest for a better postoperative opioid crossed paths with Buckenmaier’s interest in acute pain at a conference of the American Society of Anesthesiologists in New Orleans. The two doctors met, and it appeared sufentanil’s properties made it just what the Defense Department was looking for.

At that time, many American soldiers were falling victim to roadside bombs in Iraq and Afghanistan, and medics were relying on morphine shots that were often ineffective, particularly for soldiers with substantial blood loss, leaving the wounded in excruciating pain. A powerful drug that could be administered orally and held the potential to relieve pain quickly would be easier to administer on the battlefield than IV morphine, which works well but is not practical in a war zone.

Buckenmaier, according to Palmer, said he loved her idea of using sufentanil, but the military needed something twice as strong. Medics couldn’t realistically re-up individual soldiers’ pain medication every 20 minutes during a combat fight.

Dsuvia founder Pamela Palmer. (Morgan Schmidt-Feng/Yahoo News)
Dsuvia founder Pamela Palmer. (Morgan Schmidt-Feng/Yahoo News)

Soon after that, Palmer and her company applied for a Department of Defense grant to develop a more powerful version of her oral opioid pill, and the Pentagon money followed. In 2011, Palmer’s company received an initial $5.6 million contract from the Defense Department through Army Medical Research and Development Command’s Clinical and Rehabilitative Medicine Research Program. It was the first chunk of what would become a $22 million investment in the powerful new opioid.

The contract was a significant milestone for the drug, but the timing for a government-funded opioid could not have been worse: That fall the CDC issued a dire press release declaring that prescription painkiller overdoses were at “epidemic levels.”

As AcelRX collaborated with the military to develop Dsuvia over the next seven years, the opioid epidemic continued to explode in the United States. Fentanyl deaths increased 520 percent from 2009 to 2016, according to one estimate. Heroin overdoses also soared in that same period. At the same time, U.S. military casualties were falling as the U.S. drew down forces from Iraq and Afghanistan.

While battlefield deaths may have been declining, the Pentagon was still looking at how it dealt with pain from injuries. One increasingly popular option was ketamine. Military medical specialists describe ketamine as a nearly ideal battlefield drug, due to the fact that it does not slow breathing or lower blood pressure the way narcotic opioids do. It is also relatively inexpensive and easy for medics to carry.

In 2012, military medical leaders recommended that ketamine be used more often, and two years later, after traveling around Afghanistan by helicopter and talking to leaders on the ground, military trauma specialists issued a new set of guidelines: Fentanyl lollipops should be given to soldiers who were not in shock, but medics should otherwise rely on ketamine, which, as a non-opioid, doesn’t affect respiration and is ideal for patients who are losing a lot of blood.

But the Defense Department was also still investing in Dsuvia, which was beginning to draw attention in military medical circles.

A military official familiar with the Committee on Tactical Combat Casualty Care’s work, who spoke to Yahoo News on the condition of anonymity because they are not authorized to speak publicly about the Pentagon’s investment decisions, blamed a dysfunctional Defense Department culture for allocating millions to study Dsuvia without having any sense of whether it worked. In 2014, this person said, both the committee and the Pentagon’s Joint Trauma System requested a study to determine how Dsuvia compared with fentanyl lollipops.

The committee also recommended that military health leaders “explore all options” and make intramuscular ketamine auto-injectors and intranasal ketamine available to medics treating injured soldiers in the battlefield. A comparison study should have been “funded as a high-priority item, and it wasn’t,” the military official said.

Neither study was ever done.

The failure to do those studies appeared to be a disconnect between those in the Defense Department who control research and those who are responsible for determining treatment. “You don’t invest millions of dollars in a product and then not do the necessary studies to make sure that we have all of the information that we need to decide whether or not it’s better than what we’re currently using,” said the official.

Despite that, in 2015 the Defense Department awarded an additional $17 million to AcelRx to continue developing Dsuvia and help pay for stage III trials, which are designed to test the effectiveness of the drug. The military official was unaware of any other painkilling drug where the military has funded the stage III trials: “There is nothing else like this.”

If some in the Pentagon thought the military was moving too fast, for Palmer, whose company is situated in fast-paced Silicon Valley, it was a snail’s pace. “In the biotech world, if we move that slowly, we would disappear as a company,” she said, noting that her company paid for its own phase III work until the Pentagon money kicked in.

“So we actually were like, ‘Oh, my gosh, we got to do this on our own for a little, until they get caught up.’ So, in fact, we funded a lot of our first study on our own — that first phase III, because we just couldn’t keep waiting.”

By the time AcelRx was ready to submit for FDA approval, in 2017, the situation for the company was dire. At that point it had been in business for more than a decade, with nothing ready to market in the United States (its sufentanil-based product, Zalviso, was approved by the European Commission in 2015). Its fate rested largely on the FDA, and the response was not good.

In October of that year the FDA rejected Dsuvia, saying it could easily drop on the floor or in bedsheets. The agency cited the drug’s extreme potency and the relatively high number of dropped tablets in clinical trials to justify the decision. (An unusually tiny pill, Dsuvia proved difficult to position in patients’ mouths.) If a child or elderly person were to pick up and ingest a dropped dose, the FDA warned, they could die from “respiratory depression,” or not being able to breathe. “If one of those Tic Tacs drops on the floor and a child picks it up, they’re going to be dead,” says Brown, the former FDA advisory committee chair, who went public with safety concerns about Dsuvia after it was approved.

But the process was not over. AcelRX, with support from the Pentagon, reapplied for approval, conducting additional clinical trials and amending the directions for use to make them clearer and enhance safety.

The timing was fortuitous, because the FDA was in the middle of a battle with the Pentagon. The Department of Defense and its champions in Congress were frustrated by what they saw as the FDA’s slow pace in considering other drugs and devices prioritized by the military, including a blood plasma product the Pentagon urgently wanted.

At one point, Defense Department allies in Congress became so frustrated by the FDA’s slow progress that they proposed shifting the authority to approve certain high-priority battlefield drugs and medical devices from the FDA to the Pentagon. “The chairman has perfect moral clarity on this provision, and there is no doubt in his mind that it is the right thing to do for the troops,” a House Armed Services Committee spokesman told Politico at the time. (The spokesman, Claude Chafin, recently told Yahoo News that the House committee agreed with the proposal to give the Pentagon greater authority over approvals, “but this really was a Senate push.”) Scott Gottlieb, then the FDA commissioner, told the health news site STAT that the FDA “almost lost the ability to approve products for the military.”

Scott Gottlieb, commissioner of the Food and Drug Administration, answers a question as the Senate Committee on Health, Education, Labor and Pensions examines the federal response to the opioid addiction crisis, at the Capitol in 2017 in Washington. (J. Scott Applewhite/AP)
Then-FDA Commissioner Scott Gottlieb at a Senate health committee hearing on the opioid addiction crisis in 2017. (J. Scott Applewhite/AP)

The two sides were working on an agreement as these long-standing tensions boiled over, according to a person who was involved in Dsuvia’s FDA approval. Terry Rauch, the acting deputy assistant secretary of defense for health readiness policy and oversight, was “pushing to get the FDA out” of the way of the Pentagon’s priority medicines and medical devices by putting a “special carve-out” in place for Pentagon approvals, this person said.

While some in Congress were backing the Pentagon, others were worried about the opioid epidemic. Four senators weighed in to implore the agency to reject Dsuvia. The potent pill’s formulation — a small, single tablet taken orally — “allows for rapid absorption into the blood stream,” the senators wrote. “These properties also make the product highly divertible.” Fentanyl and sufentanil (the latter is Dsuvia’s chemical name) are the most common drugs for which anesthesiologists enter addiction treatment, the senators argued, and an easily consumed pill delivering a powerful high would make Dsuvia an attractive street drug.

Despite those warnings, a year after initially rejecting the drug, the FDA voted again on Dsuvia and this time approved it. This time, however, it failed to invite all but a few members of the safety committee, according to Brown, the Kentucky-based anesthesiologist, and a second committee member who spoke on the condition of anonymity. Brown, who was not invited, would later argue in a Washington Post op-ed that this move made a “favorable vote for the drug more likely because of decreased focus on safety.”

“A whole new group of new people that had some history with the FDA were inserted in the line,” Brown told Yahoo News. “One has to presume that there was a reason that they didn’t want people who were going to ask hard questions to be at the meeting.” (FDA spokesman Nathan Arnold said that while certain members couldn’t attend the meeting due to scheduling conflicts, the FDA did not disinvite anyone.)

Brown was not alone in his concerns. “This was a drug that was a solution in search of a problem,” said Steven Meisel, the patient safety director at M Health Fairview in Minneapolis, one of three members who voted against approving Dsuvia in 2018. The military, he noted, says Dsuvia is wanted for the battlefield, where inserting an IV line is not feasible. “But the problem is the studies that were done and presented to our committee were done in postoperative settings,” said Meisel. “The idea that a patient in a hospital undergoing surgery doesn’t have an IV line is absurd — that’s surgery 101.”

He said he worries that Dsuvia could cause accidental overdoses, particularly since clinical trials showed it took a surprisingly long median time of 54 minutes to offer “meaningful pain relief.” When ER or surgery patients are suffering, nurses want to help and might not carefully track when patients last received a pill, giving a second dose of Dsuvia too soon after the first. For patients who are already sicker or smaller than average, Meisel said, that raises a real risk of accidental overdose.

Brown believes that the FDA approved the drug because of pressure from the Pentagon, something the Pentagon doesn’t deny. Rauch of the DOD told Yahoo News that as a result of the pressure from Congress and the agreement between the FDA and the Pentagon that resulted from it, he now holds quarterly meetings with the FDA commissioner to monitor progress on drugs and medical devices that the Defense Department prioritizes. The agreement now in place was the result of a request for a “close collaboration and working relationship between” the Pentagon and the FDA, he said.

Terry Rauch, Acting Deputy Assistant Secretary of Defense for Health Readiness Policy and Oversight at the Department of Defense, testifies before the U.S. House Committee on Oversight and Reform in March at the United States Capitol in Washington D.C. (Stefani Reynolds/CNP via ZUMA Wire)
Terry Rauch, acting deputy assistant secretary of defense for health readiness policy and oversight at the Department of Defense. (Stefani Reynolds/CNP via ZUMA Wire)

How critical the Pentagon’s support for Dsuvia was to the approval is up for debate, but the same day that Dsuvia was approved, the FDA announced a new focus on collaborating with the Department of Defense. The initial “memorandum of understanding” authorized the FDA to “expedite the development of medical products” deemed important to the military. Gottlieb, then the FDA commissioner, also appeared to indicate that the FDA decision was influenced by the Pentagon. “I don’t want to say [Dsuvia] was only approved because we thought it had application in battlefield settings,” Gottlieb told STAT. “But this was a product priority for the military.”

AcelRX’s Palmer, however, said she didn’t think the Pentagon’s support helped with the FDA approval. “It’s been delay, delay, delay. ‘No, go back and do another study. Get older people. Get people with comorbidities. Oh, no, I’m giving you a complete response letter, because you need to change that wording and you need to put this number here,’” she said of the FDA process. “I mean, if the DOD was behind us, I don’t know what it helped.”

But the FDA did appear on the defensive about its decision. In its approval, Gottlieb included an unusual statement indicating that the agency was considering whether to begin studying new opioids not just on their “own merits” but also in light of “the epidemic of opioid misuse and abuse that’s gripping our nation.”

Gottlieb, who left the FDA in April of last year and is now a venture capitalist and a prominent national voice on the coronavirus pandemic, defended the FDA’s approval of Dsuvia as appropriate, but says the agency should have greater latitude when considering new opioids. “I think we need to have an explicit discussion in this country about whether or not there should be a higher standard applied to the approval of opioids and whether or not the agency should have the authority to look at therapeutic superiority or some kind of comparative effectiveness standard in the setting of approving new opioids,” he said in an interview earlier this year.

Opioids should be evaluated based primarily on whether they are better than what is already on the market, Gottlieb said: “In the setting of an opioid epidemic, I think the agency ought to have that authority.”

While Gottlieb supports stricter standards, he still doesn’t see Dsuvia as a unique threat. When Dsuvia was approved, he emphasized that the FDA was requiring an unusually strict safety program that had been established to protect the public. “There are very tight restrictions being placed on the distribution and use of this product,” he said at the time, citing the deaths caused by OxyContin and other opioid pills.

Those restrictions, however, have a poor track record, according to Joshua Sharfstein, an opioid expert and public health professor at Johns Hopkins University. He co-authored a study published in the New England Journal of Medicine last year showing that neither the FDA nor manufacturers monitored or punished doctors who failed to follow the rules when dispensing a highly potent class of fentanyl products known as TIRF drugs. The study, based on nearly 5,000 pages of FDA reports obtained under the Freedom of Information Act, showed that even though as many as half of patients taking fentanyl medications should not have received them, neither the FDA nor the manufacturers reviewed records for even a single physician responsible for prescribing them to ensure they were complying with agency rules.

Sharfstein said it is vital that the FDA change protocol to make the safety programs and their enforcement more transparent. The agency has historically relied too much on drug companies to implement them, he said in an interview. “And, in the end, the companies are making promises that they aren’t keeping.”

Palmer insists Dsuvia won’t be easy for addicts to get their hands on. While she acknowledges that no amount of regulation can ever be foolproof, Dsuvia is available only in medical settings, and doctors can’t write prescriptions for its use elsewhere. AcelRx also created a “single-use applicator” to make it easier for hospitals and clinics to detect if doses are stolen.

Dsuvia will be harder for medical personnel to steal than liquid morphine, Palmer said, pointing out that many addicts working in hospitals have been known to swap morphine with saline and water, leaving patients writhing in pain.

Critics aren’t convinced. Brown told Yahoo News that he has resuscitated at least three fellow anesthesiologists who have overdosed on the intravenous form of sufentanil. He said that when he has had to revive colleagues who have overdosed, his training kicks in immediately and he begins CPR. “You don’t have time to think about it being horrifying,” he said.

The controversy Brown spearheaded with his public remarks didn’t die down quickly. Advocates for drug addicts mounted a campaign decrying the decision dubbed “Wake Up FDA.” And Massachusetts Sen. Edward Markey and Colorado Rep. Diana DeGette sent Gottlieb a letter in February 2019 requesting all documents that the FDA had relied on in concluding that Dsuvia filled an unmet military need. “Sufentanil has been known for decades to be diverted in its current intravenous form,” they wrote. “It can deliver a potency that has been known to be lethal in small dosages.”

Sen. Edward Markey and Rep. Diana DeGette. (Barry Chin/The Boston Globe via Getty Images, Bill Clarke/CQ Roll Call via Getty Images)
Sen. Edward Markey, Rep. Diana DeGette. (Barry Chin/The Boston Globe via Getty Images, Bill Clarke/CQ Roll Call via Getty Images)

The FBI appears to share those concerns. The intelligence bulletin obtained by Yahoo News stated that the agency “assumes Dsuvia’s high potency will be attractive to criminals seeking to divert and abuse synthetic opioids.” The bulletin went on to note the “historic abuse and diversion of IV sufentanil, despite the strict delivery methods and limited number of medical professionals with access to the drug. The potency and ease of administration of Dsuvia tablets increase these risks.”

The bulletin’s conclusions were alarming: “Because of its potency, Dsuvia likely will cause deaths at a rate surpassing that associated with fentanyl, increasing the overall opioid-related death rate in the near term.”

The FBI declined to comment on the bulletin specifically, but a spokesperson wrote that the “illegal diversion of opioids that are required by law to be administered by a healthcare professional in a certified medically supervised setting remains a concern for the FBI and our federal, state, and local partners. Opioid prescription diversion and the illicit production of opioids contributes to the opioid epidemic our country is facing and leads to abuse and increased overdose deaths across many U.S. populations.”

Yet 13 months after that bulletin was issued, Dsuvia has not been widely diverted or misused, according to the Drug Enforcement Administration. “As with all controlled substances, we are continually working with our partners, including FDA, to monitor trends in diversion,” DEA spokesman Michael D. Miller told Yahoo News. “At present, there is very limited evidence that DSUVIA is being diverted and misused.”

Back in California, the FDA approval meant things were finally looking up for AcelRx, but time was critical for the small company. With relatively little cash on hand, only two closely related opioids in its portfolio and only one with FDA approval, it was critical that the company sell something to keep itself alive. The FDA approval for Dsuvia may have been based on the military’s interest and support, but now there was just one problem: The military wasn’t actually starting to buy the drug for battlefield use.

Despite the fact that Dsuvia advocates in the research community were funding the drug, it wasn’t clear that those responsible for buying would do so. Special Operations Command, which was thought to be one of the primary users of the drug, appears to be uninterested. “SOCOM is aware of sufentanil but did not officially request the drug,” said a spokesperson, who added that no special operations units have requested Dsuvia.

In late April, the Pentagon held a “milestone C” review for Dsuvia — which usually determines when a product is ready for military use — and approved the drug. At this point, however, no one in the military has committed to buy it, and it’s not clear they ever will. The roadside bombs that drove the initial military interest in Dsuvia have dropped precipitously as the U.S. has drawn down troops in Iraq and Afghanistan.

Lori Salvatore, a spokeswoman for the Army Medical Research and Development Command, said in a written statement that the military believes Dsuvia is a safe and effective option for treating battlefield pain. Citing “numerous advantages to our nation’s warfighters,” the statement said that Dsuvia is “safer than fentanyl with a therapeutic index nearly 100 times greater.” It also provides more consistent dosing than the fentanyl lollipop, the statement said, making it “a vital addition to the DOD’s inventory of pain management tools.”

Even so, it’s possible Dsuvia will never be widely used by the military. The Army Medical Research and Development Command doesn’t dictate what gets bought — that’s typically determined by commanders — and Dsuvia isn’t yet included in the Committee on Tactical Combat Casualty Care guidelines, and it’s unclear when that will happen, if ever.

Maj. Stephen Schauer, an emergency physician and researcher at the U.S. Army Institute of Surgical Research, says that, in theory, commanders can deviate from those guidelines and request Dsuvia, but they are not likely to do so. “I don’t think that’s going to happen anytime soon,” he said of the chances that Dsuvia will make it to the battlefield.

That may not matter to AcelRx, which is now focusing most of its efforts on the civilian market. Even though the drug’s origins are with the Defense Department, once it’s approved, Dsuvia is not restricted to military customers.

On a November call with investors, Palmer and other AcelRx executives said the company is now targeting 1,100 ambulatory surgery centers along with hospitals. The company has had more success signing contracts with ambulatory surgery centers — where colonoscopies, orthopedic surgeries and similar outpatient procedures are performed — than with hospitals, which typically move more slowly to adopt new medicines. As of November, AcelRx said, Dsuvia had been approved for use at 105 outpatient facilities, with a goal to reach 125 by the end of 2019.

Palmer said AcelRx also sees ERs a natural fit, though emergency medicine standard bearers have begun to warn clinicians about giving powerful opioids to patients who report to the emergency room with relatively minor trauma. “This is a no-brainer in an emergency room,” Palmer said in an interview at her office. “That’s like the battlefield except moved inside. You come in with a broken leg. You’re in a lot of pain. Why not give you something like this instead of jamming an IV and trying to start, do all that hassle?”

The possible uses for Dsuvia, Palmer said, are already expanding rapidly in the civilian market. The drug, she said, is proving popular with time-pressed ambulatory surgery centers and dental offices, in part because it can be used on “autopilot,” an attractive feature for ER doctors. “Oral surgeons are using it for a lot of the dental extractions that they have to do,” she added.

That description alarms critics like Andrew Kolodny, medical director of the Opioid Policy Research Collaborative at Brandeis University’s Heller School for Social Policy and Management. Removing teenagers’ wisdom teeth is among the most common forms of oral surgery, he said, and oral surgeons are the No. 1 prescribers of opioids to young adults and teenagers. It’s likely Dsuvia sales reps “are going to be making this sound like a much better product than anything else existing despite the fact that it is an extremely dangerous, potent opioid,” he said.

While AcelRx has long asserted that the FDA’s safety program, known as a Risk Evaluation and Mitigation Strategy, will keep Dsuvia from harming people, Kolodny pointed out that the wording the FDA used to limit where it can be administered — “medically supervised setting” — is nebulous at best.

AcelRX headquarters in Redwood City, CA. (Sam Matthews/Yahoo News)
AcelRx headquarters in Redwood City, Calif. (Sam Matthews/Yahoo News)

AcelRx “isn’t likely to just sit on their hands and hope that doctors prescribe this new product that they’ve invested millions in,” Kolodny said. “They will do everything they can to see a return on their investment.”

At AcelRx’s headquarters in Northern California, Palmer, whose company is now in its 15th year, is cautiously optimistic about its future, even amid the economic crisis. In fact, the opioid shortages brought on by the coronavirus pandemic have prompted renewed interest in Dsuvia, she says. “The military had reached out to us and said, ‘Hey, people are coming to us and we’re asking them, well, have you considered Dsuvia?’” So now the company is making a renewed push to hospitals, pointing out that Dsuvia could be used to help intubate patients.

Palmer acknowledged that a “couple of anesthesiologists here and there” might abuse Dsuvia, but said the federal database that tracks such abuse consistently shows that just 0.5 to 0.7 percent of abused opioids originate from medically supervised settings.

The company now has about 50 employees, 40 of whom are salespeople focused on Dsuvia. “It’s still small,” says Palmer. “It’s hard to develop and change people’s patterns of behavior and what they’re used to.”

But she’s encouraged by the fact that those who do order Dsuvia appear to like it, a lot. “We’re excited in that everyone who tries it is like, ‘Oh, my gosh, this is great,’” she says. “And they want to reorder and use it, but it’s just trying to get them to try it the first time.”

Jana Winter and Sharon Weinberger contributed reporting to this story.

Cover thumbnail Photo illustration: Yahoo News; photos AcelRX, Getty Images


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