FDA Approves the First Non-Opioid Pain Drug in 20 Years

On Jan. 30, the U.S. Food and Drug Administration (FDA) approved a new drug called suzetrigine to treat moderate-to-severe pain. The prescription pills, sold under the brand name Journavx and made by Vertex Pharmaceuticals, are taken twice a day and represent the first new class of pain medications in 20 years—and the first non-opioid painkiller since that class first appeared on the market in the 1980s.

While opioids are currently the most potent and effective way to control pain, they are associated with a significant risk of addiction, and have fueled an epidemic of addiction and overdose deaths in the U.S. in recent decades. From 1999 to 2017, deaths from overdose due to prescription opioids increased more than seven times, exposing a dire need for effective but nonaddictive ways to manage pain.

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Here’s what to know about suzetrigine.

How suzetrigine works

One major conduit for pain transmission in the human body is through sodium channels. People have nine such sodium channels in the body, and different ones are active in different tissue types, including in the brain.

Suzetrigine relieves pain by controlling the flow of sodium in and out of cells, and it targets one sodium channel that is specific to pain neurons in tissues that are found throughout the body but not in the brain. The medication therefore avoids the addictive potential of opioids, which work by binding to opioid receptors throughout the central nervous system, in both the brain and spinal cord.

Finding the right sodium channel target, however, took decades of research, which was all the more challenging since sodium channels by definition work quickly—so their effects, and the effects of any compounds designed to control them, are hard to measure. Once researchers identified the specific sodium channel that was selectively active in pain nerves, called Nav 1.8, scientists at Vertex combed through libraries of compounds to find an effective inhibitor to block the opening of the channel. “We screened hundreds of thousands of compounds looking for the needle in the haystack that inhibited 1.8,” says Paul Negulescu, senior vice president at Vertex. Animal studies were encouraging, and the company launched human studies that were completed in early 2024. Vertex submitted a request for FDA approval in July.

What the studies found

Trials included people with acute pain after two types of surgery—bunion removal and tummy tucks—that represented two major types of pain-generating injury: to bone and soft tissues, respectively. Researchers tracked people’s self-reported measures of pain for 48 hours, beginning immediately after their anesthesia wore off. People were randomly assigned to receive suzetrigine, hydrocodone-acetaminophen (an opioid), or a placebo to treat their pain.

Those receiving suzetrigine reported around a greater and faster reduction in pain compared to those taking placebo pills; among those getting abdominoplasty, 61% of those taking suzetrigine reported at least a 30% drop in pain, which researchers consider meaningful, compared to 48% taking placebo. Among those getting bunionectomy, 83% those taking suzetrigine achieved this threshold, compared to 68% of those getting placebo.

People assigned to the opioid hydrocodone and acetaminophen group reported better pain control than those taking suzetrigine, but suzetrigine doesn’t carry the risk of addiction. “We saw patients reporting huge decreases in pain,” says Dr. Jessica McCoun, an anesthesiologist who was one of the principal investigators on trials for both bunionectomy and abdominoplasty at CenExel in Atlanta, one of the trial sites. The results “make me believe that suzetrigine could replace opioid use, although I can’t say that for sure,” she says. “Any novel class of drug is a huge opportunity, since we haven’t had anything new in the pain space in 20 years.”

The company also conducted a third study of people with a wider range of pain-related conditions—both surgical and non-surgical—affecting the head, neck, shoulder, knee, foot, and ankle. In this study, patients knew they were receiving the drug. Those results also showed that suzetrigine effectively relieved pain in a variety of conditions.

Could it work for chronic pain?

Vertex is also exploring whether suzetrigine could manage chronic pain, which usually stems from a more complex and sprawling set of conditions than acute pain. Those results have been less solid so far. Among patients with sciatica, those who received suzetrigine and those who got a placebo reported similarly small reductions in pain after 12 weeks.

Still, Negulescu says the company is moving ahead with later-stage testing to better adjust for the placebo effect and better understand the drug’s effect in chronic pain. “Our belief is that the Nav1.8 mechanism is going to be relevant in both acute and chronic pain,” he says.

Chronic pain can be traced to two primary mechanisms, Negulescu says. One affects muscles and bone—in arthritis and low back pain, for example—in which nerves remain intact, but tissues surrounding them are damaged and start sending pain signals. Another type of chronic pain occurs when the nerves themselves are damaged, which occurs in conditions like diabetes, especially in peripheral tissues like fingers and feet. “We believe the mechanism of suzetrigine is relevant in both musculoskeletal and neuropathic pain,” says Negulescu. “Our working hypothesis, based on the data we have, is that Nav1.8 is still expressed and present in chronic conditions.”

How the approval could change pain management

As effective as suzetrigine is, it doesn’t completely eliminate it. “Patients still feel pain; they don’t go to zero pain sensation,” says Negulescu. But, he believes, suzetrigine shows that it may be possible to get better at precisely controlling the sodium-channel pain signal to achieve greater pain management. “We are entering a new era where we may be able to more safely and specifically inhibit pain, and that will change our relationship to and how we think about pain,” he says.

Dr. Todd Bertoch, chief medical officer for pain research at CenExel in Utah, who was the lead investigator on the suzetrigine studies, also notes that the pills were associated with relatively few side effects—a major distinguisher from opioids. “This is the first study I have ever conducted where the side-effect profile for people on placebo was worse than the side-effect profile for people on the study drug,” he says.

Where suzetrigine will fit into the pain-management landscape remains to be seen, but experts see its potential in treating more serious pain, if over-the-counter remedies don’t work. Ideally, pain experts believe it could be the first-line treatment after surgeries and minor procedures, including dental procedures, instead of the opioids that are currently prescribed.

Bertoch says opioids may continue to have a place in treating certain kinds of pain, but suzetrigine gives doctors another option. “Suzetrigine lets me add another tool that doesn’t have liver toxicity, doesn’t have kidney toxicity, is very safe, and is at least additive and maybe even synergistic with acetaminophen and ibuprofen,” he says. “It fills a gap where otherwise we have used opioids.”