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With over 2.1 million Americans struggling with opioid use disorder and more than 80,000 lives lost to opioid overdoses in 2022 alone, the need for alternatives to opioid painkillers has never been more urgent.[1][2] These highly addictive drugs, while effective for pain management, come with dangerous risks of dependence and overdose.
In a groundbreaking move, the FDA approved Journavx (suzetrigine) on January 30th—the first non-opioid pain medication in two decades.[3] As the first drug in a new class of painkillers, Journavx offers a novel approach by inhibiting pain signals at the nerve level, providing effective relief without the risks associated with opioids.
Because non-opioid alternatives are limited in the current healthcare landscape, opioids have often been the go-to solution—even when their dangers may outweigh the benefits. Journavx’s approval marks more than just the arrival of a new drug; it could be a pivotal moment in the effort to combat opioid dependency and reshape pain management, shifting toward safer, non-addictive treatments.
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What is Journavx (suzetrigine)?
Journavx, developed by Vertex Pharmaceuticals, uses a novel approach to reducing pain by targeting a specific sodium channel involved in pain signaling, NaV1.8.[4][5]
As the active ingredient in Journavx, suzetrigine inhibits the transmission of pain signals to the brain and spinal cord by selectively inhibiting NaV1.8 voltage-gated sodium channels.
Unlike opioids, which act on the brain’s opioid receptors to dull pain and can induce euphoria (which, in turn, fuels addiction), suzetrigine works peripherally, directly blocking pain at the nerve level.[1][4]
This distinction makes it an exciting alternative for those who need effective pain relief without the risks of dependence and overdose.
How does Journavx work?
Pain perception is heavily influenced by sodium channels, particularly NaV1.8, which plays a critical role in transmitting pain signals from the site of injury to the brain. Journavx works by selectively inhibiting NaV1.8, preventing those pain signals from reaching the brain in the first place.[4]
This is a significant departure from traditional pain medications, which either block pain at the brain level (opioids) or reduce inflammation (NSAIDs).
How is it different from opioid painkillers?
Because Journavx does not activate opioid receptors and acts peripherally in the body before reaching the brain, it lacks the euphoric high that makes opioids so dangerously addictive. This different mechanism of reducing pain results in a much lower risk of dependence.
It also doesn’t cause the severe side effects of opioid use, particularly respiratory depression, a primary cause of overdose deaths.
The most commonly reported side effects of Journavx in clinical trials included itching, muscle spasms, increased blood level of creatine phosphokinase (CPK), and rashes. This is a much less severe side effect profile than opioid painkillers.[5]
These differences could make suzetrigine a game-changer for post-surgical pain, injury-related pain, and chronic pain conditions, offering relief without the risk of opioid dependency.
Does that mean it isn't addictive?
Based on clinical trials, the risk of addiction appears significantly lower than opioids, but no drug is entirely risk-free.[5] Journavx is new, and long-term studies are needed to determine its full safety profile.
Current data suggests it does not trigger the brain’s reward system in the same way opioids do, making addiction far less likely.[7]
That being said, the misuse of pain medications can go beyond their pharmacology, potentially leading to psychological dependence, which means real-world data is imperative to confirm their true potential for abuse.
Other non-opioid painkillers
Journavx isn’t the only non-opioid painkiller currently in development.
Biotechs like Latigo Bio are advancing LTG-001, an oral NaV1.8 blocker designed for acute pain, which works similarly to Journavx. CEO Desmond Padhi believes it has the potential to be the best in its drug class.[7]
Sangamo Therapeutics and Korro Bio are focusing on a different method for non-opioid pain relief, using a gene-editing approach, targeting NaV1.7 to reduce pain signaling at the genetic level.
Lexicon Pharmaceuticals is developing pilavapadin, an AAK1 inhibitor aimed at treating chronic neuropathic pain, while South Rampart Pharma’s SRP-001 is a non-toxic alternative to acetaminophen that provides central pain relief without liver damage.[7]
Other contenders include Algiax’s AP-325, a small-molecule GABAA activator for neuropathic pain, Xgene’s XG005, an investigational oral analgesic, and Tris Pharma’s cebranopadol, a dual nociceptin and opioid receptor agonist now nearing FDA submission.[7]
What do non-opioid painkillers mean for healthcare?
The U.S. opioid epidemic has claimed hundreds of thousands of lives, largely due to overprescription and the addictive nature of these drugs.[1]
A safer alternative like Journavx could reduce the need for opioids in post-operative and acute pain settings, making a dent in opioid dependency rates. Plus, with the growing number of non-opioid painkillers in the pipeline, the landscape of pain management may begin transforming over the coming years. This could lead to a paradigm shift where opioids are reserved for only the most severe cases rather than being the go-to pain solution.
Hopefully, this will result in safer pain management options and lower rates of addiction.
What happens next?
While Journavx is now approved, widespread adoption will take time. Physicians need to be educated on its use, insurance coverage must be sorted, and real-world efficacy and safety data will continue to be gathered.
The price of this new medication will also play a role in its prescription, as currently, a single 50 mg pill costs around $15, with a recommended dosage of 100 mg daily, totaling around $30 a day. In comparison, opioids cost as little as $1.25 per pill. These higher costs can deter patients from using the drug and may influence insurance coverage.
The approval of Journavx doesn’t mean opioids will no longer be used, but they will likely be reserved for severe cases refractory to other methods of pain control. If Journavx delivers on its promise, we could be looking at one of the most important breakthroughs in pain management in decades.
Medical professionals are hopeful yet cautious. New drugs always generate excitement, but it is imperative to remain vigilant to ensure they truly benefit patients without unintended consequences.
Final thoughts
Journavx is not a silver bullet for the opioid crisis, but it’s a major step in the right direction.
If it can replace even a fraction of opioid prescriptions, that means fewer people may be at risk for addiction, overdose, and long-term dependency.
The real test will be in how well it is integrated into pain management without repeating the mistakes of the past.
Medical professionals will be watching closely—and hoping that this time, we get it right.
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