Investigational Sodium Channel Blocker Effective as Treatment for Moderate-to-Severe Acute Pain

VX-548 (suzetrigine; Vertex Pharmaceuticals, Boston, MA), a selective Na_V1.8 inhibitor, was shown to be effective as a treatment for moderate-to-severe acute pain according to recent study results. Vertex Pharmaceuticals reported data from 2 phase 3 studies evaluating the safety and efficacy of VX-548 for acute pain after bunionectomy and abdominoplasty, as well as a single-arm phase 3 clinical trial evaluating the safety and effectiveness of the agent in treating surgical and nonsurgical pain (NCT05661734). Treatment with VX-548 was associated with statistically significant improvement in pain compared to placebo. Na_V1.8 is a voltage-gated sodium channel blocker that plays a role in pain signaling in the peripheral nervous system.

In the abdominoplasty and bunionectomy studies, the primary outcome measures were time-weighted sum of the pain intensity difference from 0 to 48 hours (SPID48) and clinically meaningful reduction in pain from baseline at 48 hours according to the Numeric Pain Rating Scale (NPRS). For people who received an abdominoplasty, the least squares mean difference in SPID48 was 48.4 for VX-548 vs placebo (95% CI, 33.6 to 63.1; P<.0001). For bunionectomy, the least squares mean difference in SPID48 was 29.3 for VX-548 vs placebo (95% CI, 14.0 to 44.6; P=.0002). VX-548 also met a key secondary endpoint in both studies, showing a more rapid onset to meaningful pain relief vs placebo, as measured by a ≥2-point reduction in NPRS from baseline. VX-548 was associated with fewer AEs than placebo in both studies. However, VX-548 was not shown to be superior to hydrocodone bitartrate/acetaminophen (HB/APAP) as measured by SPID48.

In the single-arm phase 3 study, participants received VX-548 every 12 hours for 14 days. The primary outcome measure was safety and tolerability as assessed by the number of participants who experienced adverse events (AEs) or serious adverse events (SAEs). VX-548 was shown to be safe and well tolerated, and 83.2% of participants rated the medication as “good”, “very good”, or “excellent” in treating pain.

“As a physician treating patients suffering from pain for many years, I know firsthand the critical need for new, efficacious and safe treatment options,” said Jessica Oswald, MD, MPH, Associate Physician in Emergency Medicine and Pain Medicine, University of California San Diego. “The Phase 3 safety and efficacy across the three studies are impressive and demonstrate VX-548’s potential to change the paradigm of pain management. I look forward to the potential of having a new class of acute pain medicine—the first in more than two decades—to use as an alternative to opioids to help the millions of people impacted by acute pain.”