Suzetrigine, a Non-Opioid Na_V1.8 Inhibitor With Broad Applicability for Moderate-to-Severe Acute Pain: A Phase 3 Single-Arm Study for Surgical or Non-Surgical Acute Pain

Affiliations

¹ Cenexel Georgia, Atlanta, GA, USA.
² Anaheim Clinical Trials, Anaheim, CA, USA.
³ Clinical Investigation, HD Research, LLC, Bellaire, TX, USA.
⁴ Orthopedic Surgery, OrthoNebraska, Omaha, NE, USA.
⁵ CenExel JBR Clinical Research, Salt Lake City, UT, USA.
⁶ Department of Emergency Medicine, UC San Diego Health, San Diego, CA, USA.
⁷ Department of Anesthesiology, Center for Pain Medicine, UC San Diego, San Diego, CA, USA.
⁸ Arizona Research Center, Phoenix, AZ, USA.
⁹ Global Patient Safety, Vertex Pharmaceuticals, Boston, MA, USA.
¹⁰ Biostatistics, Vertex Pharmaceuticals, Boston, MA, USA.
¹¹ Clinical Development, Vertex Pharmaceuticals, Boston, MA, USA.
¹² Research, Vertex Pharmaceuticals, Boston, MA, USA.
¹³ Global Medicines Development and Affairs, Vertex Pharmaceuticals, Boston, MA, USA.
¹⁴ Emergency Medicine, Brigham and Women's Hospital, Boston, MA, USA.

PMID: 40165940
PMCID: PMC11955400
DOI: 10.2147/JPR.S509144

Suzetrigine, a Non-Opioid Na_V1.8 Inhibitor With Broad Applicability for Moderate-to-Severe Acute Pain: A Phase 3 Single-Arm Study for Surgical or Non-Surgical Acute Pain

Jessica McCoun et al. J Pain Res. 2025.

. 2025 Mar 25:18:1569-1576.

doi: 10.2147/JPR.S509144. eCollection 2025.

Authors

Affiliations

¹ Cenexel Georgia, Atlanta, GA, USA.
² Anaheim Clinical Trials, Anaheim, CA, USA.
³ Clinical Investigation, HD Research, LLC, Bellaire, TX, USA.
⁴ Orthopedic Surgery, OrthoNebraska, Omaha, NE, USA.
⁵ CenExel JBR Clinical Research, Salt Lake City, UT, USA.
⁶ Department of Emergency Medicine, UC San Diego Health, San Diego, CA, USA.
⁷ Department of Anesthesiology, Center for Pain Medicine, UC San Diego, San Diego, CA, USA.
⁸ Arizona Research Center, Phoenix, AZ, USA.
⁹ Global Patient Safety, Vertex Pharmaceuticals, Boston, MA, USA.
¹⁰ Biostatistics, Vertex Pharmaceuticals, Boston, MA, USA.
¹¹ Clinical Development, Vertex Pharmaceuticals, Boston, MA, USA.
¹² Research, Vertex Pharmaceuticals, Boston, MA, USA.
¹³ Global Medicines Development and Affairs, Vertex Pharmaceuticals, Boston, MA, USA.
¹⁴ Emergency Medicine, Brigham and Women's Hospital, Boston, MA, USA.

PMID: 40165940
PMCID: PMC11955400
DOI: 10.2147/JPR.S509144

Abstract

Background: Many patients experience inadequate pain control due to limited options that are both efficacious and safe for treating moderate-to-severe acute pain; therefore, opioids are still frequently prescribed for their effectiveness despite known tolerability issues and safety concerns. Suzetrigine, an oral, non-opioid, offers a promising alternative by selectively inhibiting the voltage-gated sodium channel 1.8 (Na_V1.8), a novel therapeutic target for pain management. Given the high selectivity of suzetrigine for Na_V1.8 (does not bind to other sodium channels/receptors with CNS activity), suzetrigine does not have CNS side effects or addictive potential associated with opioids. In the largest randomized, controlled phase 3 trials in established acute pain models, suzetrigine monotherapy demonstrated statistically significant and clinically meaningful reduction in moderate-to-severe acute pain compared to placebo.

Methods: To evaluate the safety and effectiveness of suzetrigine for the treatment of moderate-to-severe-acute surgical and non-surgical pain conditions, we conducted a phase 3, single-arm study in adults with moderate or severe acute pain on the verbal categorical rating scale and ≥4 on the numeric pain rating scale following surgical procedures or after presenting to a medical facility with moderate or severe acute pain of new origin. Participants received suzetrigine (100mg then 50mg every 12hrs) for 14 days or pain resolution, whichever came first. The primary endpoint was safety. The secondary endpoint was participant perception of suzetrigine's effectiveness in treating acute pain at the end of treatment using a patient global assessment.

Results: Suzetrigine was generally safe and well-tolerated in participants (N=256) with a range of surgical and non-surgical acute pain conditions; the maximum severity for most participants who had adverse events was mild (71 participants; 27.7%) or moderate (21 participants; 8.2%). Most participants (213 participants; 83.2%) rated suzetrigine's effectiveness for treating pain on a patient global assessment as good, very good, or excellent.

Conclusion: Suzetrigine provides a safe and effective non-opioid, non-addictive treatment with broad applicability for moderate-to-severe acute pain.

Clinicaltrialsgov registration: NCT05661734.

Keywords: NaV1.8 inhibitor; VX-548; moderate-to-severe acute pain; non-opioid; surgical/nonsurgical acute pain; suzetrigine.

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Conflict of interest statement

Drs. McCoun, Solanki, Urban, Bertoch, Oswald, Swisher, Taber, and Weiner have reported personal fees from Vertex Pharmaceuticals as members of the Acute Pain Steering Committee. Dr. Urban has reported personal fees and honoraria from Pacira Biosciences. Dr. Oswald participates on a Data Safety Monitoring Board for Salix Pharmaceuticals. Dr. Swisher reports funding paid to his institution from SPR Therapeutics, Infutronix, and Avanos Medical, during the conduct of the study. Drs. Healey, Jazic, Correll, Negulescu, and Bozic are employees of Vertex Pharmaceuticals and own stock and/or options in the company. Dr. Weiner reports personal fees from Cessation Therapeutics, Inc., outside the submitted work. The authors report no other conflicts of interest in this work.

Figures

**Figure 1**
Study Participants. Includes participants who received at least one dose of suzetrigine. (A) shows surgical participants categorized by surgery type. (B) shows non-surgical participants categorized by region.

**Figure 2**
Patient Global Assessment. Includes participants who received at least one dose of suzetrigine. (A) shows the proportion of participants reporting good, very good, or excellent on the PGA at the end of suzetrigine treatment and (B) shows these data separately for surgical and non-surgical participants.

See this image and copyright information in PMC

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Suzetrigine, a Non-Opioid Na_V1.8 Inhibitor With Broad Applicability for Moderate-to-Severe Acute Pain: A Phase 3 Single-Arm Study for Surgical or Non-Surgical Acute Pain

Affiliations

Suzetrigine, a Non-Opioid Na_V1.8 Inhibitor With Broad Applicability for Moderate-to-Severe Acute Pain: A Phase 3 Single-Arm Study for Surgical or Non-Surgical Acute Pain

Authors

Affiliations

Abstract

Conflict of interest statement

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References

Associated data

LinkOut - more resources

Full Text Sources

Medical