Opioids provide extremely quick pain relief — within a single minute when injected directly into the bloodstream. But they come with a high cost: Opioids are highly addictive due to their direct activation of opioid receptors involved in the brain’s reward circuitry. In 2022 alone, more than 80,000 Americans died from an opioid overdose (1). Novel non-opioid pain medications are urgently needed, but none had been approved in more than 20 years.
That finally changed on January 30th when the FDA approved the non-opioid oral pill Journavx (suzetrigine) from Vertex Pharmaceuticals to treat moderate-to-severe acute pain in adults.
“It's really exciting for the field. We haven't had a win in a very long time,” said Theodore Price, a neuroscientist at the University of Texas at Dallas. “It’s going to have a huge impact. And I also think it's going to be amazing to have a tool that we can use so that we don't have to expose some of the patients to opioids.”
It's really exciting for the field. We haven't had a win in a very long time.
– Theodore Price, University of Texas at Dallas
Journavx works by blocking the voltage-gated sodium channel 1.8 (NaV1.8) found on nerve cells that process pain outside of the brain. Sodium channels like NaV1.8 are involved in amplifying pain signals after injury, but previous attempts to block NaV1.7 resulted in safety issues, including cardiovascular adverse events (2). Vertex Pharmaceuticals did not observe the same side effects with Journavx. In two clinical trials of over 2,000 patients who underwent either a tummy tuck or bunion removal surgery, Journavx provided significantly more pain relief than a placebo pill while showing an “amazing” safety margin, Price said. The most common side effects were itching, skin rashes, muscle spasms, and an increased level of creatine phosphokinase, an enzyme involved in regulating metabolism.
“I like that it works by a different mechanism, and that it has a much more favorable side effect profile than opioids, which are the gold standard,” said Steven Cohen, an anesthesiologist and pain researcher at Northwestern University.
Vertex Pharmaceuticals researchers also showed that the pain relief from Journavx was about the same as taking the opioid hydrocodone with acetaminophen (the two active ingredients in Vicodin). But unlike opioids, clinicians and scientists aren’t worried about patients becoming addicted to Journavx. “There really is no NaV1.8 in the brain. I cannot come up with a mechanism through which [addiction] could happen,” said Price. Instead, he added that Journavx represents a successful validation of the idea that blocking signals from pain neurons outside of the brain can have a large influence on pain. Moving forward, Price and Cohen said that further research will focus on improving upon the approach to block NaV1.8 and other sodium channels for acute pain relief. Researchers in the field also aim to apply this approach to treat other types of pain, like chronic pain.
For now, despite the societal benefits of a non-opioid pain drug, Cohen said we may not see widespread use of Journavx due to its high cost compared to opioids. “There are always limits on costly drugs. And the limits will come from hospitals that don't want to lose money, and they'll come from [insurance] payers,” he said. “That's why when IV acetaminophen was approved, a lot of hospitals limited it to certain populations, and it had to be approved by pain services.” In an encouraging sign, UnitedHealth Group’s pharmacy benefit manager, OptumRx, recently announced that Journavx will likely be included in its prescription coverage, pending their formal review. However, it will be placed in tier 3, meaning that it will cost patients more money out-of-pocket than generic opioids.
Price also suggested that with similar drugs now in development behind Journavx, competition could bring the price down. But right now, he is more concerned about how the recent attacks on National Institutes of Health (NIH) funding and the firings of thousands of federal workers at the NIH, CDC, and FDA by President Trump’s administration will affect the United States’ scientific enterprise. “In pain, specifically, we have made so much progress in the last five years, and this whole [Journavx approval] is evidence of it,” he said. Price explained that the mechanistic work for a NaV1.8 drug came from academic labs, though he emphasized Vertex deserves credit for developing the drug and getting it to FDA approval. “Even though it's a third of the population the United States that suffers from some kind of pain problem, we were in an amazing position to make a huge impact on it. And maybe we won't lose all our momentum, but it seems very dangerous right now to me.”
References
- Hébert, A.H. & Hill, A.L. Impact of opioid overdoses on US life expectancy and years of life lost, by demographic group and stimulant co-involvement: a mortality data analysis from 2019 to 2022. Lancet Reg Health Am 36, 100813 (2024).
- Regan, C.P. et al. Autonomic Dysfunction Linked to Inhibition of the Nav1.7 Sodium Channel. Circulation 149, 1394–1396 (2024).
