Can Journavx replace opioids?
Journavx is finally in the wild. Widely touted as an opioid replacement, it hit the market this year — the first new type of non-opioid pain medication to be approved by the FDA in twenty years.1 Most media coverage of Journavx has been extremely positive. The New Yorker:
Scientists working in pain research described the underlying scientific achievement as “a magisterial first step,” “just marvellous,” and “the holy grail.”
Okay, technically that was scientists being extremely positive, not the media — but the media has certainly run with that enthusiasm in a big way. I do not love that New Yorker article, because it reads like a poetic press release. The salamander’s take is more cynical, of course. That is how the salamander earns his kibble here.
So let’s look at some of the not-so-great news about Journavx now that it’s actually being prescribed. First some review: why would anyone call this drug the “holy grail” of analgesia? What’s the big idea?
Journavx makes peripheral nerves less trigger happy
The generic name of the drug is suzetrigine (Wikipedia), branded as Journavx (“JOR-na-viks”) by the manufacturer, Vertex Pharmaceuticals. It’s a peripheral nerve channel blocker, the result of many years of research into the mind-bogglingly complex mechanistic details of how nerves work. This was a very long scientific journey. Michelle Ma for the Works in Progress Newsletter:
Vertex chose to keep funding and pushing forward through decades of work that industry professionals describe as ‘tedious’, ‘mind-numbing’, and ‘painstaking’, a slog driven by slow, incremental progress and frequent setbacks. In exchange, humanity now has its first non-opioid painkiller.2
The point of this drug is to block pain “at the source,” by reducing the sensitivity of peripheral nerves to nociception. Nociception is the transduction of damage or danger into nerve impulses, and not quite equivalent to pain — although any large dose of nociception usually does lead to pain!
Journavx raises the threshold at which those signals are generated in the first place.
More specifically, it makes peripheral nerve cells less sensitive by clogging their NaV1.8 sodium channels. This means that the drug cannot be addictive, because it doesn’t tinker with the brain: no “reward” physiology. And there’s no tolerance or dependence either, because those sodium channels don’t adapt in a clinically significant way to the drug — so it doesn’t change how you work, and therefore there are no withdrawal symptoms to endure.
And … it works well enough to have gotten approved. Yazhtzee! This all sounds great. And of course in some ways it is.
Theory, meet reality: Journavx (and cousins) don’t seem to work as well as they “should”
The principle makes a sodium-channel blocker seem like a slam dunk: how could it disappoint? But disappoint it does. The principle is clearly not a free pass to perfect pain relief.
For instance, a closely related candidate drug in Vertex’s pipeline, VX-993, recently failed its Phase 2 trial. But Journavx had some subtle special sauce that enabled it to stumble across the finish line that VX-993 couldn’t even reach, despite the fact that they are practically the same thing.3 Makes you wonder.
Despite being good enough for approval, the efficacy data for Journavx is underwhelming: only high doses were even modestly effective, and still could not actually beat weak opioids for acute pain.4 Journavx’s approval was based on its ability to do more than a placebo, of course, but it’s pain-relieving power was similar to that of hydrocodone (more potent than codeine, but much less than oxycodone, morphine, etc).
That might replace some opioids, but clearly not the strong ones, and probably not even the weak ones for all patients.
This doesn’t mean Journavx is useless, of course, far from it. If you can’t get relief from your garden variety pain killers for a nasty acute pain, Journavx is now there for you as a next step up, more effective than codeine and maybe as effective as hydrocodone and less problematic — and that truly is something to celebrate.
Chronic pain patients are definitely not celebrating the arrival of Journavx
Journavx got approval for acute pain only, not chronic pain — which would have been very important for patients, and extremely lucrative for Vertex. But Journavx didn't beat a placebo for sciatica in a Phase 2 trial.5 That New Yorker article understated the implications egregiously: “it remains unclear if Journavx will be helpful with chronic pain, cancer pain, or neuropathic pain.”
Yes, it’s “unclear” … and unlikely based on the evidence we’ve seen so far.
Other Journavx caveats
Journavx is also a bit “slow” — opioids typically have a clear effect within half an hour, and peak after a couple hours. Journavx takes a couple hours to be noticeable. Vertex can’t honestly put “fast relief” in the marketing!
And it’s expensive: roughly USD $900 for a month supply, which is something like 10–15 times more expensive than the cheap-like-borscht weak opioids. The economics matter, and it’s difficult to overstate how much more they matter in the context of the opioid war, where it’s not just the efficacy of opioids that will be traded in, but their truly greater affordability.
While the safety profile looks pretty good so far, it’s not perfect, and long-term safety is obviously still unknown and hardly assured — which is normal for a new drug, of course, but still a consideration for the millions of people who will have prescriptions for this drug offered to them.
Offered … or rammed down their throats?
“You’ll take this non-opioid pain killer and you’ll like it”
I fear that many patients who need strong opioids will be given Journavx instead, and many of those cases may be tragic.
In the context of the opioid war, Journavx will probably be over-prescribed and its value over-estimated just because it is not an opioid. In a healthy healthcare system, that wouldn't be a profound statement. But we're in the middle of a vicious war on opioids, and the people who actually need them, demonizing them as contemptible "drug seekers," equating any need/usage with addiction. I wish I was exaggerating. If anything, I’m understating how bad it has gotten.
“We’ve swallowed the lie that anyone who uses opioids is just one step away from the gutter,” writes David Manny in “The Forgotten Casualties of the Opioid War.”
The systemic appetite for something, anything to replace opioids is at an all-time high (and that’s saying something). There are now disastrously intense incentives to overlook any shortcomings of any drug that touts itself as an “opioid replacement.” We have already seen how this works with the anticonvulsants, which are a far less credible replacement for opioids, and yet they have been used that way in a big way.
In other words, this new drug may be “like crack” for prescribers right now — to use an absurdly apt ironic metaphor.
Journavx is an interesting drug that likely has an important place in healthcare. And there’s still reasonable hope that this approach to analgesia will eventually produce something that we can take more seriously as an “opioid replacement.”
Meanwhile, I won’t be adding Journavx to my list of “what works” for chronic pain — because it doesn’t. Not that we can tell from the evidence so far.
That’s a lot of bad news about literally the first serious advance in analgesia in many years, and it really sucks. It is a serious disappointment that this “next generation” pain-killer — the result of so much hard work by so many very smart people — is just riddled with caveats.
Notes
- A review article states: “Before suzetrigine’s approval in 2025, the most recent FDA-approved novel pain medication was celecoxib in 1998.” Celecoxib is a COX-2 selective NSAID (same class as ibuprofen). Obviously, other more conventional analgesics have had incremental changes and new formulations have been approved, e.g.Voltaren (topical diclofenac) for osteoarthritis. But Journavx is definitely the first new class of pain-killer.
- Actually, there are a few other “non-opioid pain killers”! Aside from this odd distortion — which even made it into the title, “The first non-opioid painkiller” — it’s a great article about Journavx, probably the best I’ve seen, and well worth reading after this one if you’re keen on the topic.
“Vertex non-opioid pain candidate fails Phase 2 trial.” StatNews.com.
What was the difference? Maybe due to pharmacokinetics, insufficient selectivity, or maybe they just tested it badly somehow — mistakes happen!
- Bertoch T, D'Aunno D, McCoun J, et al. Suzetrigine, a Nonopioid Na V 1.8 Inhibitor for Treatment of Moderate-to-severe Acute Pain: Two Phase 3 Randomized Clinical Trials. Anesthesiology. 2025 Jun;142(6):1085–1099. PubMed 40117446 ❐ PainSci Bibliography 49314 ❐
- Vertex Pharmaceuticals Incorporated. A Phase 2 Study of VX-548 in Participants With Lumbosacral Radiculopathy. ClinicalTrials.gov Identifier: NCT05406648. Press release. The trial met its within-group primary endpoint, and of course Vertex emphasized this … but investors weren't buying it. Within-group results alone just don’t cut it in clinical trials. The comparison to placebo is what matters … and the placebo arm improved almost the same amount, and the study wasn’t powered for a direct drug-vs-placebo comparison. So that landed with a clunk, and investors were very disappointed.