On January 30th, in a landmark decision that could reshape the way acute pain is treated in the United States, the FDA approved suzetrigine (brand name, Journavx), a first-in-class non-opioid analgesic that is an alternative to traditional painkillers. This long-awaited development comes at a time when although overdose deaths from legally prescribed opioids have decreased significantly in recent years, there remains the stigma of opioid use, the reluctance of some physicians to prescribe them, and the burden of government controls on them
With its innovative mechanism of action and promising clinical trial results, suzetrigine offers hope for millions suffering from moderate to severe acute pain.
A Paradigm Shift in Pain Treatment
Suzetrigine’s approval is significant not just because it provides an alternative to opioids, but because it represents a new class of pain medication with a novel mechanism of action. Unlike opioids, which work by binding to receptors in the brain and spinal cord, suzetrigine targets sodium channels in the peripheral nervous system before pain signals even reach the brain. Essentially, it acts as a targeted pain signal blocker at the source in the peripheral nerves. Thereby, it reduces the risk of addiction associated with opioids while still offering effective pain relief.
The drug was evaluated in rigorous clinical trials that demonstrated its efficacy in patients recovering from two common surgical procedures — abdominoplasty (excision of abdominal fat and skin for cosmetic purposes) and surgical removal of bunions. In these studies, patients who took suzetrigine reported statistically significant reductions in pain compared to those given a placebo.
Also, patients who needed additional pain relief were allowed to take ibuprofen (Advil), which suggests that suzetrigine could be used in combination with other non-opioid medications to optimize pain management strategies. This point is important, given that suzetrigine alone is not exactly a world-beater when it comes to pain relief. As my colleague, chemist Dr. Josh Bloom, wrote about the drug in January of last year:
As a key secondary endpoint, Vertex tested the hypothesis that VX-548 [suzetrigine] was superior to hydrocodone bitartrate/acetaminophen (Vicodin) on SPID48 following abdominoplasty surgery or bunionectomy surgery. Neither trial met this critical secondary endpoint. (Emphasis in original.)
Here's a problem that was not explicitly mentioned. Not only did VX-548 fail to demonstrate superiority over Vicodin, but also that of the two most common oral opioids given following surgery, Percocet (oxycodone) and Vicodin – Vicodin is the weaker drug. Furthermore, the dose of Vicodin used in the trial was 5 mg – the lowest therapeutic dose of the drug. So it's safe to say that VX-548/Suzetrigine will not fare better against a more potent opioid and/or higher dose.
Only future real-world experience – perhaps in combination with other non-opioid drugs, as mentioned above -- will determine the importance and acceptance of suzetrigine.
Addressing the Opioid Crisis
The FDA’s approval of suzetrigine aligns with the Agency’s broader efforts to combat opioid addiction through its Overdose Prevention Framework. Over the past decade, the FDA has encouraged the development of non-opioid pain treatments, issued guidance to facilitate their approval, and provided funding for research on alternative pain management strategies. The approval of suzetrigine is a testament to these efforts and marks the first time in more than 20 years that a novel pain drug has been authorized by regulators.
For pharmaceutical companies, healthcare providers, and policymakers, the potential impact of suzetrigine could be significant. Vertex Pharmaceuticals, the maker of the drug, has positioned it as a game-changer in acute pain management since more than 80 million people in the U.S. are prescribed medication for moderate to severe acute pain each year. If widely adopted, suzetrigine could greatly reduce the number of opioid prescriptions issued, potentially preventing thousands of cases of opioid dependency.
Economic and Policy Considerations
Despite its clinical promise, suzetrigine faces significant hurdles in achieving widespread adoption. The cost of the drug — $15.50 per 50-milligram pill, or $31 for a standard starting dose — could make it less attractive than cheap, generic opioids which remain the dominant choice for pain management in hospitals and clinics. Insurers and healthcare providers may be hesitant to switch unless clear, real-world benefits emerge, such as reduced hospital stays, lower rates of opioid addiction, or better overall patient outcomes.
Regulatory and policy dynamics also play a role in the drug’s future. The FDA’s decision to approve suzetrigine was particularly notable given the current political climate. Early on, the Trump administration imposed a temporary freeze on external communications from federal health agencies, making the announcement published by the FDA a high-profile exception to the new directive.
The appointment of Robert F. Kennedy Jr. as Secretary of Health and Human Services looms large over the broader regulatory landscape. The idiosyncratic, science-challenged Kennedy, who has been critical of mainstream medicine and pharmaceutical companies, could create new obstacles for companies like Vertex.
The future of non-opioid drug development, including potential expansion of suzetrigine’s indications for chronic pain, may hinge on the Trump administration’s approach to medical innovation.
The Road Ahead: Hopes, Skepticism, and Uncertainty
While the FDA’s approval of suzetrigine has been met with enthusiasm in many quarters, some experts caution that its impact remains uncertain. Clinical trials have shown strong results in controlled settings, but whether the drug will deliver the same benefits in a variety of real-world scenarios remains to be seen.
Some analysts have tempered expectations, particularly following a trial in sciatica patients that failed to demonstrate a significant advantage over placebo. Also, suzetrigine has thus far only been shown to work in acute pain settings — and it is in the chronic pain arena where the need for safer, non-opioid alternatives is most pressing.
The economic viability of suzetrigine also has been a topic of debate. The Institute for Clinical and Economic Review, a nonprofit organization that evaluates prescription drug cost-effectiveness, has suggested that the drug could be only slightly more cost-effective than opioids if priced at around $420 per week. The calculation is based on estimates of how many opioid addiction cases the drug might prevent, an area where precise data are elusive.
Despite these concerns, the approval of suzetrigine is, undeniably, a milestone. It signals that the pharmaceutical industry is making progress in developing effective non-opioid pain treatments, and it challenges the healthcare system to rethink its approach to pain management. If suzetrigine proves successful, it could pave the way for a new generation of safer painkillers, ultimately reducing reliance on opioids and lowering the risk of addiction.
Conclusion: A Step Forward in Pain Management
The FDA’s approval of suzetrigine represents potentially important step in addressing the nation’s pain management crisis. While questions remain about its cost, adoption, and long-term efficacy, its novel mechanism and positive clinical results offer a promising alternative to opioids. For policymakers, healthcare providers, and patients alike, the introduction of suzetrigine presents both an opportunity and a challenge: an opportunity to embrace an innovative treatment that may reduce reliance on opioids and a challenge to ensure that such new therapies are accessible, affordable, and truly beneficial.
Henry I. Miller, MS, MD
Henry I. Miller, MS, MD, is the Glenn Swogger Distinguished Fellow at the American Council on Science and Health. His research focuses on public policy toward science, technology, and medicine, encompassing a number of areas, including pharmaceutical development, genetic engineering, models for regulatory reform, precision medicine, and the emergence of new viral diseases. Dr. Miller served for fifteen years at the US Food and Drug Administration (FDA) in a number of posts, including as the founding director of the Office of Biotechnology.
