FDA Approves Non-Opioid Pain Medication Suzetrigine (Journavx™)

The Food and Drug Administration (FDA) recently approved a new, non-opioid prescription pill—suzetrigine. Sold under the brand name Journavx™, the drug is helpful in treating moderate-to-severe acute (short-term) pain in adults.

Medical experts say suzetrigine, which is made by Vertex Pharmaceuticals, is not addictive because it works by blocking pain signals that originate in the peripheral nervous system, before they reach the brain. In contrast, opioid medications attach to certain receptors in parts of the body, including the brain, where they can not only block pain but also can elicit pleasurable feelings. Opioid addiction can develop if the brain begins to crave those euphoric effects.

To address the opioid epidemic that has emerged in the United States, it’s become increasingly important to find effective, non-opioid pain management strategies. From 1999 to 2022, nearly 727,000 people died in the U.S. from an opioid overdose, including prescription and illegal opioids, according to the Centers for Disease Control and Prevention (CDC).

Given the severity of this problem, Journavx is believed to be an important step in the right direction. “For pain physicians, the holy grail of medication management is something that can block pain with no side effects,” says Robert Chow, MD, a Yale Medicine anesthesiologist and pain management specialist. “We have effective medications for treating pain and improving function, but the ideal scenario is one that works as well as opioids, but without the untoward side effects.”

Journavx, however, is not a cure-all. It is meant for moderate-to-severe acute pain, or pain that starts suddenly (often from trauma or surgery) and is expected to last less than three months. This means, based on the current evidence, that it would likely be used primarily in the hospital setting and only for a few days, says Dr. Chow. Though no date has been specified, the drug will be available by prescription as well. The medication is not intended for chronic pain, but the clinical trials did show that it had some efficacy in treating diabetic peripheral neuropathy (nerve damage that can cause numbness in extremities) when compared to a standard treatment, Dr. Chow notes.

Stephen Waxman, MD, PhD, a Yale School of Medicine neuroscientist, and his research team laid the foundation for the development of Journavx and similar drugs more than 25 years ago when they showed that Nav1.8—a “molecular battery” that produces nerve impulses—is needed for pain signaling within peripheral nerves, but not within the brain.

“Based on that finding, multiple biopharma companies have attempted to develop new drugs that block Nav1.8, with the hope that they would block pain signaling at the source—the nerves—but have no effect on the brain,” explains Dr. Waxman, who was not involved with Vertex’s development of Journavx.

For now, price might be an obstacle for Journavx. The medication, which comes in 50-milligram tablets, has a list price of $15.50 per pill, and most people would need to take two a day. By comparison, a common painkiller such as Vicodin (a combination of acetaminophen and the opioid hydrocodone) is $1 to $2 per pill. It’s not yet known if insurance companies will cover its cost and for which conditions.

To understand Journavx’s mechanism of action, it helps to review how the brain receives pain signals—and the role sodium channels play in transmitting them. When you get injured, for example, from stepping on a nail, pain-sensing nerve cells in the injured area respond by producing nerve impulses that they send as a signal, like Morse code, to the brain.

Those nerve impulses are produced by molecules called sodium channels, which are found in the membranes of nerve cells. The sodium channels act like gates, and when they open, they allow charged particles called sodium ions to enter the nerve cell. The electrical currents of the sodium channels create the nerve impulses that carry the pain signal to the brain.

Sodium channel blockers are substances that stop sodium channels from operating, preventing the nerves from sending pain messages to the brain as effectively, which can reduce or eliminate pain.

Journavx is not the first medication that blocks sodium channels. Novocaine, a local anesthetic widely used in dental offices, is a sodium channel blocker, but it is not selective. This means it doesn’t target a particular sodium channel; instead, it numbs the area where it is applied. Journavx, however, acts within the peripheral nervous system to block Nav1.8, which Dr. Waxman’s team showed is responsible for sending pain signals to the brain. The medication reduces the pain signals before they can reach the brain.

Suzetrigine was tested in two large clinical trials, each with about 1,000 patients who experienced moderate-to-severe pain after surgery. Participants were assigned to three groups: One received a placebo, one got the opioid Vicodin, and the third was given suzetrigine.

One of the trials involved patients who had an abdominoplasty (tummy tuck); the other involved patients who had a bunionectomy (bunion removal). Both trials showed that suzetrigine eased pain as effectively as Vicodin, and both medications provided more pain relief than the placebo.

Vertex also submitted safety data from a study of about 250 people who received suzetrigine after experiencing pain from other types of surgery, trauma, or accidents.

One weakness of the study, Dr. Chow says, is that it compared suzetrigine to Vicodin instead of to other, stronger opioids like oxycodone, morphine, hydromorphone, and fentanyl. “Plus, the surgeries in the studies are outpatient procedures that typically do not require significant pain management and are amenable to regional or local pain blocks,” Dr. Chow says.

In addition to being nonaddictive, suzetrigine does not cause nausea or drowsiness, which are common issues with opioid medications. The studies found that the most common side effects of suzetrigine include itching, muscle spasms, and rash.

People should not take Journavx if they take certain medications, including the antibiotic erythromycin and the blood pressure/angina medication verapamil, which are strong inhibitors of CYP3A, a liver enzyme. Food or drink that contains grapefruit can also interfere with the medication and should be avoided. Journavx can also increase a certain blood enzyme called creatine phosphokinase, which can be a measure of tissue injury in the muscle, heart, and brain.

Journavx may temporarily reduce the chance of becoming pregnant, but women who use contraceptives should continue using them while being treated with the medication, Vertex says.

Dr. Waxman and colleagues, including Dmytro Vasylyev, PhD, a Yale School of Medicine research scientist in neurology, have been investigating how blocking certain sodium channels could reduce chronic neuropathic pain, including numbness in the hands or feet.

Journavx reduces pain after injury or surgery, but does not totally relieve it. Dr. Waxman’s team is attempting to design sodium channel blockers that will be more effective than Journavx for acute pain. And they are exploring approaches that will relieve long-term chronic pain as it occurs in diabetic neuropathy. Dr. Waxman is also studying how gene therapy might help prevent pain by altering the mechanism of peripheral sodium channels.

Journavx was approved for acute pain, but there are other types of pain for which there aren’t many good treatments, including peripheral neuropathic pain, as mentioned above.

For example, existing pain medications are not effective in sciatica, pain that radiates from the lower back down one leg due to a compressed nerve. In small studies so far, Vertex found that suzetrigine helped people with diabetic neuropathy but was no better than a placebo for sciatica. Larger studies are continuing.

In an article in The New England Journal of Medicine that accompanied Vertex’s report of their positive results with Journavx for acute pain, Dr. Waxman characterized the development of the medication as a milestone, not because it is totally effective, but rather because it provides “proof of concept” that, via the strategy of blocking Nav1.8, it is possible to reduce pain in humans.

“This is a first step,” Dr. Waxman says. “We have more work to do, but I expect that next-generation drugs will be even better.”