Study Supports Safety of Suzetrigine as Non-Opioid Treatment for Pain after Orthopaedic Surgery

Research presented at the AAOS 2025 Annual Meeting shows that the oral drug suzetrigine has potential to be a safe and effective option to manage moderate to severe acute pain, such as that experienced after orthopaedic surgery. This non-opioid pain medication is currently in development and may be the first in a new class of pain medications.

“Moderate to severe acute pain after orthopaedic surgery is frequently treated with opioids because of the lack of non-opioid treatment options with favorable benefit-risk profiles,” wrote the authors of this poster study, which was presented at the 2025 AAOS Annual Meeting by Joshua Aaron Urban, MD, FAAOS, joint-replacement specialist at OrthoNebraska in Omaha, Nebraska. Although commonly prescribed, opioids come with risks such as the development of addiction and misuse. Therefore, orthopaedic surgeons and patients need other pain-management options.

Suzetrigine efficacy
The voltage-gated sodium channel 1.8 (NaV1.8) may be a good therapeutic target involved in moderate to severe pain. It is selectively expressed on peripheral nociceptors and has a role in the transmission of pain signals. Suzetrigine is a potent and highly selective inhibitor of NaV1.8. Because of its mechanism of action, the drug carries no risk of addiction or misuse.

Two recent randomized, double-blind, placebo-controlled, phase 3 studies assessed the efficacy of suzetrigine in patients who had just had either abdominoplasty (n = 1,118 dosed) or bunionectomy (n = 1,073 dosed). In those cohorts, suzetrigine treatment reduced pain compared with placebo.

Utility for orthopaedics
The current study was a safety analysis of a single-arm, open-label, phase 3 study investigating suzetrigine in 256 patients with moderate to severe acute pain from a broader range of causes, including surgical and nonsurgical. The patients experienced pain after having a scheduled surgical procedure or after presenting to a medical facility with acute pain of new origin. They rated baseline pain as moderate or severe on a verbal categorical rating scale and ≥4 on a numeric pain rating scale ranging from 0 to 10. Suzetrigine dosing was 100 mg for the first dose, then 50 mg every 12 hours for 14 days or until resolution of pain.

The safety analysis included data from 93 patients with acute pain after orthopaedic surgery. The mean (SD) duration of suzetrigine treatment was 11.7 (4.2) days. The study found that suzetrigine was generally safe and well tolerated, with no serious adverse events reported. Mild to moderate adverse events included headaches, which affected 7.5 percent of participants.

At the end of treatment, most of the participants (89.2 percent) rated suzetrigine’s effectiveness as good, very good, or excellent. This was congruent with results from the overall study (83.2 percent).

Dr. Urban’s coauthors of “Suzetrigine, a Non-Opioid Selective Pain Signal Inhibitor, Is Effective in Treating Acute Pain Following a Broad Range of Orthopaedic Surgery-Related Procedures” are Daneshvari R. Solanki, MD; Tiffany Healey, MD; Theodore Huang, PhD; Darin J. Correll, MD; Paul Adrian Negulescu, PhD; James Jones, MD; Carmen Bozic; and Scott Weiner, MD, MPH.

Keightley Amen, BA, ELS, is a freelance writer for AAOS Now.

Reference

Osteen JD, Immani S, Tapley TL, et al: Pharmacology and mechanism of action of suzetrigine, a potent and selective NaV1.8 pain signal inhibitor for the treatment of moderate to severe pain. Pain Ther 2025 Jan 8.