FDA Approves Nonopioid Pain Medication in Novel Class for Treatment of Acute Pain

On January 30, 2023, the FDA approved suzetrigine (Journavx), a first-in-class nonopioid analgesic, for managing moderate to severe acute pain in adults. Suzetrigine, preclinically characterized as VX-548, is a highly selective inhibitor of the voltage-gated sodium channel NaV1.8.

NaV1.8 is a sought-after therapeutic target for pain, given its role in transmitting nociceptive signals in peripheral, dorsal root neurons. This is a new therapeutic target and, therefore, a class to be identified in the nonopioid category for the management of acute pain.

The new approval is the first nonopioid option for moderate to severe acute pain in adults. | Image Credit: DedMityay - stock.adobe.com

EFFICACY

Two phase 3, randomized, double-blind, placebo-controlled clinical trials (VX22-548-105 [NCT05558410] and VX22-548-104, [NCT05553366]) evaluated the safety and efficacy of suzetrigine compared with placebo and an opioid analgesic (hydrocodone bitartrate/acetaminophen). Participants were enrolled if they met the criteria for moderate to severe acute pain following an abdominoplasty (VX22-548-105, n=1118) or bunionectomy (VX22-548-104, n=1075).^1,2

The primary efficacy outcome evaluated was the mean difference in time-weighted sum of the pain-intensity difference over 48 hours (SPID 48) in both treatment groups (abdominoplasty, n = 447; bunionectomy, n = 426) compared with placebo group (abdominoplasty, n = 223; bunionectomy, n = 216). These scores use patient-reported numeric pain rating scale scores. SPID 48, reported using the least square mean, was 37.8 (95% CI, 9.2-66.4) in the abdominoplasty population and 36.8 (95% CI, 4.6-69.0) in the bunionectomy population.^1,2

SAFETY

Investigators analyzed safety data from the 2 trials’ pooled data. Less than 1% of patients discontinued suzetrigine (0.6%), hydrocodone/acetaminophen (0.6%), or placebo (0.2%) early on due to adverse events. The most reported reasons for premature discontinuation in the suzetrigine group were postprocedural hematoma and hypotension (both 0.2%). Adverse reactions reported in less than 1% of patients in the suzetrigine groups and greater than that of placebo were pruritus (2.1%; placebo, 1.6%; hydrocodone/acetaminophen, 3.4%), muscle spasms (1.3 %; placebo, 0.5%; hydrocodone/acetaminophen, 0.7%), increased blood creatinine phosphokinase (1.1%; placebo, 0.5%; hydrocodone/acetaminophen, 0.8%), and rash (1.1%; placebo, 0.5%; hydrocodone/acetaminophen, 0.7%).^1,2

Supportive safety data from an open-label study (NCT05661734) evaluating acute pain following a surgical procedure or nonsurgical condition were consistent with safety data observed from the pooled analysis.³

DOSING AND ADMINISTRATION

Suzetrigine is available as a 50-mg tablet. The recommended dosing is a loading dose of 100 mg, followed by 50 mg every 12 hours.⁴ The loading dose should be taken on an empty stomach, and subsequent doses with or without food. It should be used for the shortest duration needed to establish treatment goals. Concomitant use with strong CYP3A4 inhibitors is contraindicated, and use in patients with severe hepatic impairment (Child-Pugh class C) should be avoided.⁵

REFERENCES

1. Evaluation of e cacy and safety of VX-548 for acute pain after an abdominoplasty. ClinicalTrials.gov. Updated August 27, 2024. Accessed February 21, 2025. https://clinicaltrials.gov/study/NCT05558410

2. Evaluation of e cacy and safety of VX-548 for acute pain after a bunionectomy. ClinicalTrials.gov. Updated December 16, 2024. Accessed February 21, 2025. https://clinicaltrials.gov/study/NCT05553366

3. A single-arm study to evaluate safety and effectiveness of VX-548 for acute pain. ClinicalTrials.gov. Updated December 12, 2024. Accessed February 21, 2025. https://clinicaltrials.gov/study/NCT05661734

4. Jones J, Correll DJ, Lechner SM, et al; VX21-548-101 and VX21-548-102 Trial Groups. Selective inhibition of NaV1.8 with VX-548 for acute pain. N Engl J Med. 2023;389(5):393-405. doi:10.1056/NEJMoa2209870

5. Journavx. Package insert. Vertex Pharmaceuticals Incorporated; 2025.