Suzetrigine Phase 3 Trials in Moderate to Severe Acute Pain

Key Takeaways

• Suzetrigine met the placebo comparison on the SPID48 primary endpoint in both postoperative pain trials.
• Superiority versus hydrocodone bitartrate/acetaminophen was not shown on the first key secondary endpoint in either study.
• Meaningful pain relief occurred faster than with placebo, and adverse events were similar to those seen in postsurgical settings and were mild to moderate.

In phase 3 suzetrigine trials, adults with postoperative pain after abdominoplasty or bunionectomy had placebo-controlled benefit over 48 hours.

The studies enrolled 1,118 patients after abdominoplasty and 1,073 after bunionectomy. Participants were randomized after surgery to suzetrigine 100 mg followed by 50 mg every 12 hours, hydrocodone bitartrate/acetaminophen 5/325 mg every 6 hours, or placebo for 48 hours. Suzetrigine is an oral nonopioid small molecule that selectively inhibits NaV1.8. The primary endpoint was SPID48, a time-weighted sum of pain intensity difference on the numeric pain rating scale from 0 to 48 hours versus placebo.

Both trials met the primary endpoint on SPID48 versus placebo. After abdominoplasty, the least squares mean difference was 48.4, with a 95% CI of 33.6 to 63.1 and P < 0.0001. After bunionectomy, the corresponding difference was 29.3, with a 95% CI of 14.0 to 44.6 and P = 0.0002. Neither trial met the first key secondary endpoint of superiority versus hydrocodone bitartrate/acetaminophen on SPID48. The authors characterized pain reduction with suzetrigine as similar to that seen with hydrocodone bitartrate/acetaminophen.

On the timing endpoint, suzetrigine produced a faster time to a 2-point or greater reduction in numeric pain rating scale versus placebo in both trials. After abdominoplasty, the times were 119 minutes with suzetrigine and 480 minutes with placebo, with nominal P < 0.0001. After bunionectomy, the times were 240 minutes and 480 minutes, respectively, with nominal P = 0.0016. Adverse events were similar to those seen in postsurgical settings and were mild to moderate in severity.

These findings reflect the reported postoperative outcomes over 48 hours in the two surgical cohorts.