AcelRx’s controversial under-the-tongue opioid nod sparks rare defense from FDA chief

Scott Gottlieb FDA
FDA Commissioner Scott Gottlieb argued AcelRx’s opioid Dsuvia offers an alternative when IV opioid is impractical. (FDA)

Under the heat of an addiction epidemic is perhaps the worst of times to approve a new opioid in the U.S. But the FDA granted AcelRx’s sufentanil-based Dsuvia—ten times the strength of the already high-powered fentanyl—a green light anyway.

A 30 microgram sufentanil tablet that’s put under the tongue, Dsuvia is now approved to manage acute pain in adults, despite an outpouring of concerns over the drug’s potential role in the U.S. fight against the opioid crisis and even doubts about its efficacy and safety profile.

It was no ordinary FDA review, and not only because its Anesthetic and Analgesic Drug Products Advisory Committee chair, Raeford Brown, wrote a letter pleading with the agency to reject it. Commissioner Scott Gottlieb also made a rare separate statement to explain. But the noise around the approval didn’t stop AcelRx from planning a launch early next year or Jefferies analyst Roger Song from projecting more than $500 million in peak U.S. sales.

Using the $140 overall cost of starting an IV opioid—including materials like the catheter and the drug itself—as a reference, AcelRx plans to price Dsuvia at $50 to $60, which means that even two doses of Dsuvia would still “remain competitive,” said AcelRx CEO Vince Angotti on a conference call on Monday.

Here’s the twist: The opioid won’t be available at retail pharmacies for patients to take home. It must be administered by a healthcare professional in a medically supervised setting, such as hospitals and emergency rooms, under a restrictive risk-management plan mandated by the FDA.

That restriction could turn out to be a double-edged sword. On the one hand, it limits the drug’s uptake and hence sales, but on the other, as executives pointed out on the call, the drug poses low risk for potential abuse—a feature that could ease some public anxiety over yet another opioid option.

RELATED: 1 year after FDA snub, advisory committee recommends AcelRx's Dsuvia for approval 10-3

“Our goal is not to expand the opioid market,” said AcelRx CEO Vince Angotti on the call. “However, when the healthcare professional has already decided that the opioid class of medication is the best option to treat a patient in acute pain, we believe Dsuvia provides a compelling alternative.” In fact, according to Chief Medical Officer Pamela Palmer, the 30 mcg dose is already the “minimally effective” amount as demonstrated in clinical studies.

The FDA chief also came to the agency’s defense in a rare move on a drug approval. “There are very tight restrictions being placed on the distribution and use of this product,” Gottlieb wrote in a long statement Friday that even cited potential military use as a reason for clearing it.

But is it really necessary to have a new opioid drug based on an existing active ingredient? Gottlieb appears to think so. Dsuvia “has some unique features in that the drug is delivered in a stable form that makes it ideally suited for certain special circumstances where patients may not be able to swallow oral medication, and where access to intravenous pain relief is not possible,” he said.

According to the company’s executives, initiating IV lines come with logistical delays and potential difficulties accessing veins, not to mention medication errors, as compared to a single-dose tablet. The convenience of using Dsuvia could mean a better experience for patients, they said.

Each year, about 92 million patients visit hospitals for moderate-to-severe acute pain, and among them about 18 million receive an IV only to manage pain. That’s the initial market Dsuvia will target, said Angotti. Currently 3,000 hospitals meet the company’s target criteria based on emergency volume, outpatient surgery volume, among other criteria, and the company will aim at first aim for 1,260 of them, he said.

But pricing and potential misuse aren’t the only questions Dsuvia might have to face. As Jefferies’ Song mentioned in a Friday note to clients, citing an FDA advisory committee discussion on Dsuvia back in October, the agency's experts weren't fully convinced by the drug’s efficacy and safety profile, even though they voted 10-3 in favor of its approval.  

RELATED: Pfizer manufacturing ills mean ongoing shortages for hospitals

Some questions remained around its onset of action and a lack of data comparing the drug head-to-head against IV morphine. Besides, doses must be given at least an hour apart, which could become burdensome for providers. And to use it, medical professionals must go through mandatory training.

“With this approval, AcelRx may need to prepare adequate materials/information to educate/convince prescribers that Dsuvia is a safe, effective, and practical alternative to current treatment options,” wrote Song.

But at the same time, Angotti also pointed to some FDA committee discussion around opioid injectable shortages vis-à-vis Pfizer’s manufacturing hiccups, as well as Dsuvia’s simplicity in dosing, as indications of a strong marketing opportunity.

Outside of the commercial space, Dsuvia, developed under help from the Department of Defense, could also sign up some military contracts for use in battlefield—a factor Gottlieb also played up in his statement.