On Jan. 30, the U.S. Food & Drug Administration (FDA) approved suzetrigine (Journavx, formerly VX-548), a first-in-class, non-opioid analgesic tablet, for the treatment of adults with moderate to severe acute pain. The agent reduces pain by selectively inhibiting NaV1.8, a voltage-gated sodium channel that is a pain-signaling pathway in the peripheral nervous system.1
The FDA initially accepted the new drug application for suzetrigine for priority review in July 2024. The agent ultimately received FDA fast track and breakthrough therapy designations for the treatment of moderate to severe acute pain.2
The Research
In clinical trials of more than 2,000 patients aged 18–80, suzetrigine was evaluated for pain efficacy. In a phase 2 study in patients with painful diabetic neuropathy, suzetrigine was well tolerated and effective, showing a statistically significant improvement in post-surgical pain intensity.3
The current FDA approval is supported by two randomized, double-blind, placebo- and active-controlled trials that evaluated suzetrigine’s efficacy for acute post-surgical pain. One trial evaluated patients post-abdominoplasty, and the other evaluated patients post-bunionectomy.3,4
In rheumatology, many patients first present with pain complaints. Although these preapproval clinical studies were conducted in post-surgical pain relief, the drug is approved to treat moderate to severe acute pain and holds promise for the treatment of other types of pain.
In these studies, suzetrigine exhibited statistically significantly superior reductions in pain compared with placebo. Also, patients with inadequate pain relief were allowed to use ibuprofen as a rescue medication as needed. Both studies evaluated the time-weighted sum of the pain intensity difference from 0 to 48 hours (SPID48), compared with placebo, as well as a clinically meaningful reduction in pain from baseline at 48 hours on the Numeric Pain Rating Scale (NPRS), as primary end points. The primary end points described below were met:
- Abdominoplasty: the least square (LS) mean difference in SPID48 between VX-548 and placebo=48.4 (95% confidence interval [CI]: 33.6, 63.1; P<0.0001); and
- Bunionectomy: LS mean difference in SPID48 between VX-548 and placebo=29.3 (95% CI: 14.0, 44.6; P=0.0002).
Secondary end points: A key secondary end point tested the hypothesis that suzetrigine would be superior to hydrocodone bitartrate/acetaminophen (HB/APAP) on SPID48 post-surgery. Neither clinical trial achieved this secondary end point.
The next key secondary end point of both studies was the time to meaningful pain relief, defined as a ≥2-point reduction in the NPRS from baseline compared with placebo. In both studies, patients taking suzetrigine experienced a faster onset to meaningful pain relief compared with patients taking placebo, meeting the end point. The median time to meaningful pain relief for placebo-treated patients was eight hours in both clinical trials, compared with two hours for suzetrigine-treated patients in the abdominoplasty trial and four hours for suzetrigine-treated patients in the in bunionectomy trial.
Most of the safety data for suzetrigine was based on pooled, double-blind, placebo- and active-controlled trials of patient post-surgery (n=874), with supportive safety data from a single-arm, open-label study in patients (n=256) with different acute pain conditions. The most common adverse reactions include itching, muscle spasms, increased creatine phosphokinase blood levels, and rash. No serious adverse events were reported in clinical trials.
Suzetrigine Use
Suzetrigine is available as 50 mg tablets. The recommended starting dose is 100 mg taken on an empty stomach at least one hour before or two hours after eating. Clear liquids may be consumed during this interval. At 12 hours after the starting dose, 50 mg of suzetrigine can be taken orally and administered every 12 hours with or without food. The medication should be taken for the shortest duration possible that is consistent with individual patient treatment goals. Suzetrigine for this indication has not been studied beyond 14 days of use.4
Suzetrigine is contraindicated for concomitant use with strong or moderate CYP3A inhibitors, such as fluconazole and itraconazole. It should be avoided with strong and moderate CYP3A inducers, such as rifampin, efavirenz and Saint John’s wort. Patients should avoid food or drink containing grapefruit when taking suzetrigine.
Also, patients taking suzetrigine while using hormonal contraceptives containing progestins other than levonorgestrel and norethindrone should use a back-up contraceptive method (i.e., additional non-hormonal contraceptives) or alternative contraceptives (i.e., a combined oral contraceptive containing ethinyl estradiol as the estrogen and levonorgestrel or norethindrone as the progestin, or an intrauterine system). These additional contraceptive methods should be used throughout suzetrigine treatment and for 28 days after suzetrigine discontinuation.
Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.
References
- FDA approves novel non-opioid treatment for moderate to severe acute pain [news release]. U.S. Food & Drug Administration. 2025 Jan 30.
- Vertex announces FDA acceptance of new drug application for suzetrigine for the treatment of moderate to severe acute pain [news release]. Vertex Pharmaceuticals Inc. 2024 Jul 30.
- Vertex announces positive results from the VX-548 phase 3 program for the treatment of moderate to severe acute pain [news release]. Vertex Pharmaceuticals Inc. 2024 Jan 30.
- Highlights of prescribing information: Journavx (suzetrigine) tablets. U.S. Food & Drug Administration. 2025 Jan 30.
