Vertex Pharmaceuticals (VRTX) Study Result summary

Study design and objectives

• Phase II/2, randomized, double-blind, placebo-controlled study evaluated suzetrigine, a selective NaV1.8 inhibitor, in 218 patients with painful lumbosacral radiculopathy (LSR) lasting over 3 months.

• Patients were randomized to suzetrigine 69 mg once daily or placebo after a 7-day run-in to establish baseline pain; demographics and baseline characteristics were balanced.

• Primary endpoint was within-group change from baseline in weekly average pain intensity (NPRS) at week 12; secondary endpoints included sleep interference and safety/tolerability.

• Background NSAID use was allowed and balanced; acetaminophen permitted as needed.

• Study aimed to assess treatment effect, placebo effect, and 12-week safety profile.

Efficacy and placebo response

• Suzetrigine achieved a statistically significant and clinically meaningful -2.02 point reduction in NPRS at week 12.

• Placebo group showed a similar -1.98 point reduction, resulting in no separation between treatment and placebo.

• High placebo response and site-to-site variability were observed, with some sites showing much higher placebo effects.

• Post-hoc analyses of lower placebo response sites showed separation between suzetrigine and placebo, supporting efficacy.

• Efficacy results for secondary endpoints were consistent with the primary endpoint.

Safety and tolerability

• Suzetrigine was well tolerated over 12 weeks, with a 22.9% adverse event (AE) rate versus 32.4% for placebo.

• Most AEs were mild or moderate; no serious AEs related to suzetrigine and no discontinuations due to AEs in the suzetrigine arm.

• No clinically significant trends in labs, ECGs, or vital signs; no issues with creatinine or renal function.

• High subject retention (>90%) in both arms; acetaminophen used as rescue medication by ~80% in both groups.

• One serious AE in suzetrigine group, two in placebo; no deaths in either group.