One of us leads the FDA’s advisory committee on anesthetic and analgesic drug products. The other is a former member of the FDA’s drug safety advisory committee. We write out of a sense of alarm over the FDA’s recent decision to approve another super-potent opioid.
Two weeks ago, despite being aware that a new version of an opioid, sufentanil, has limited efficacy and no unique benefits — and that an older version has been abused by health professionals — the agency approved a new, under-the-tongue version of the drug under the brand name Dsuvia. The drug is similar to fentanyl, the synthetic opioid that has been wreaking havoc on our streets and causing fatal overdoses to skyrocket — except Dsuvia is five to 10 times more potent.
Why did the agency fail to fully recognize the dangers of this drug? It can’t be because of its effectiveness. In fact, clinical trials suggested it is far less effective than proponents claim.
Dsuvia was designed, in part, to provide pain relief for our soldiers on the battlefield. But the clinical trials for the drug did not reflect the kind of medical conditions — such as massive trauma or shock — for which it would be used in a real-world military setting. Instead, Dsuvia was tested on patients following minor surgical procedures. Dsuvia required nearly an hour, on average, to meet the standard of clinically meaningful pain relief, suggesting it would not meet the needs of injured soldiers.
Rejecting Dsuvia should have been a no-brainer. An FDA-approved intravenous version of sufentanil has been used by clinicians only in hospital settings for general anesthesia and for epidurals during labor and delivery for more than 20 years. But research shows that, along with fentanyl, it is one of the two most diverted and abused drugs by anesthesiologists. One of us (Brown) has witnessed the drug’s potency firsthand,
attempting to resuscitate doctors and other health-care providers — some successfully but others not.
Because it is so potent, the dosing volume, whether in the IV version or the tiny under-the-tongue pill form, is quite small. It thus lends itself to being stolen by medical personnel for personal use, conceivably for sale. We predict that such diversion, abuse and death will be encountered within the early months of its availability on the market.
Yet the process through which the FDA approved this drug raises serious questions. Two months before the Oct. 12 advisory committee meeting at which Dsuvia was considered, the FDA disinvited the members of its drug safety advisory committee who had been invited except for three, as members of the committee told one of us (Wolfe), making a favorable vote for the drug more likely because of decreased focus on safety. An agency spokeswoman said input from drug safety and risk experts was “taken very seriously,” even though most of the drug safety committee wasn’t there.
Does the military, which partially funded the clinical trials on Dsuvia, know there is no evidence that any of the trials confirm a unique utility for the drug in a battlefield setting? Is the military comfortable using a drug that may not perform as well as available analgesics, such as intravenous morphine? No competent medic would use an under-the-tongue analgesic that takes an hour to achieve meaningful pain relief if he can, instead, quickly insert an IV line and get pain relief in minutes using older opioids.
Dsuvia will add to the flood of opioids that are feeding the epidemic. Its approval sends another signal that the FDA does not recognize the risk to public health of encouraging more opioids rather than offering incentives to create new classes of non-opioid analgesics that are effective and safe.
Opioids can provide safe relief for acute pain when prescribed rationally, but all opioids can cause serious harm. Our experience over the past decade is that the more opioids that are available, the higher the likelihood of harm for patients and the general public.
The FDA too often encourages the pharmaceutical industry to invest in more opioids. When many of those products come to be reviewed, the agency appears to believe there is no option other than to continue to flood the market. When asked why, the agency laments the requirement to maintain a level playing field. In too many cases, the product must only show up to get a stamp of approval from an agency that denies its complicity in creating or furthering the opioid fiasco and continues to ask questions about the regulation of opioids that have been answered many times by outside and in-house experts.
Too often, the agency is playing a deadly game of maintaining a level playing field for the industry while not assuring the same for the public. It is far past time to ask the hard question: When will they ever learn?