Suzetrigine, a Non-Opioid NaV1.8 Inhibitor With Broad Applicability for Moderate-to-Severe Acute Pain: A Phase 3 Single-Arm Study for Surgical or Non-Surgical Acute Pain

Abstract

Jessica McCoun,1 Peter Winkle,2 Daneshvari Solanki,3 Joshua Urban,4 Todd Bertoch,5 Jessica Oswald,6,7 Matthew W Swisher,7 Louise Anne Taber,8 Tiffany Healey,9 Ina Jazic,10 Darin J Correll,11 Paul A Negulescu,12 Carmen Bozic,13 Scott G Weiner14 On behalf of the VX-548-107 Study Team1Cenexel Georgia, Atlanta, GA, USA; 2Anaheim Clinical Trials, Anaheim, CA, USA; 3Clinical Investigation, HD Research, LLC, Bellaire, TX, USA; 4Orthopedic Surgery, OrthoNebraska, Omaha, NE, USA; 5CenExel JBR Clinical Research, Salt Lake City, UT, USA; 6Department of Emergency Medicine, UC San Diego Health, San Diego, CA, USA; 7Department of Anesthesiology, Center for Pain Medicine, UC San Diego, San Diego, CA, USA; 8Arizona Research Center, Phoenix, AZ, USA; 9Global Patient Safety, Vertex Pharmaceuticals, Boston, MA, USA; 10Biostatistics, Vertex Pharmaceuticals, Boston, MA, USA; 11Clinical Development, Vertex Pharmaceuticals, Boston, MA, USA; 12Research, Vertex Pharmaceuticals, Boston, MA, USA; 13Global Medicines Development and Affairs, Vertex Pharmaceuticals, Boston, MA, USA; 14Emergency Medicine, Brigham and Women’s Hospital, Boston, MA, USACorrespondence: Carmen Bozic, Vertex Pharmaceuticals, 50 Northern Avenue, Boston, MA, 02210, USA, Email [email protected]: 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 (NaV 1.8), a novel therapeutic target for pain management. Given the high selectivity of suzetrigine for NaV 1.8 (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.Clinicaltrials.gov Registration: NCT05661734.Keywords: suzetrigine, VX-548, non-opioid, NaV1.8 inhibitor, moderate-to-severe acute pain, surgical/nonsurgical acute pain

Keywords

• suzetrigine
• vx-548
• non-opioid
• nav1.8 inhibitor
• moderate-to-severe acute pain
• surgical/nonsurgical acute pain