Vertex Pharmaceuticals (VRTX) Study Result summary

Study design and methodology

• Two large phase 3 randomized, controlled trials (NAVIGATE 1 and 2) evaluated suzetrigine, a selective Nav1.8 inhibitor, in over 2,000 subjects with moderate-to-severe acute pain after abdominoplasty or bunionectomy, using FDA-accepted models and endpoints.

• Subjects were randomized to suzetrigine, hydrocodone-acetaminophen (HB/APAP), or placebo, with ibuprofen available for rescue pain relief; demographics and baseline characteristics were balanced.

• Primary endpoint was SPID over 48 hours versus placebo; key secondary endpoints included comparison to HB/APAP and time to meaningful pain relief.

• A single-arm phase 3 study assessed safety and effectiveness in diverse surgical and non-surgical acute pain conditions in real-world settings.

• Phase 3 data will be presented at the ASA annual meeting in October 2024, with abstracts featured in oral and poster sessions.

Efficacy and safety results

• Both phase 3 studies met the primary endpoint, showing statistically significant and clinically meaningful pain reduction versus placebo as monotherapy and as part of multimodal therapy.

• Suzetrigine reduced pain by 47% (abdominoplasty) and 51% (bunionectomy) from baseline at 48 hours, with rapid onset of pain relief (median time to ≥2-point NPRS reduction as low as 91–119 minutes vs. 180–480 minutes for placebo).

• Did not show superiority to hydrocodone-acetaminophen in SPID48 but had a more favorable safety profile.

• Lower incidence of adverse events with suzetrigine than both HB/APAP and placebo; most AEs were mild or moderate, with headache, constipation, and nausea most common.

• Discontinuation due to AEs was low, and no serious adverse events were considered related to suzetrigine.

Open-label and broader use findings

• Open-label study in 256 subjects across various surgical and nonsurgical pain conditions showed high patient satisfaction and minimal opioid use.

• Over 83% rated suzetrigine effectiveness as good, very good, or excellent; only four withdrew due to lack of efficacy.

• Most common adverse event was headache; two serious adverse events were unrelated to suzetrigine.