Suzetrigine phase II study shows significant pain reduction

The study met its primary endpoint with statistically significant and clinically meaningful reduction in pain on the numeric pain rating scale (NPRS).

Efficacy Results; The study’s primary endpoint was a within-group change from baseline in the weekly average of daily leg pain intensity on the NPRS at Week 12. This 11-point scale ranges from 0 (no pain) to 10 (worst pain imaginable). The suzetrigine arm showed a statistically significant and clinically meaningful within-group reduction from baseline in pain with a mean change in NPRS at Week 12 of -2.02. The study also included a placebo reference arm which showed a similar within-group reduction from baseline in pain with a mean change in NPRS at Week 12 of -1.98. The study was not designed nor powered for statistical comparison between suzetrigine and placebo.Vertex also conducted post-hoc analyses to further evaluate the efficacy results. These showed that there was variability in the placebo response across study sites, a recognized issue in pain trials. In the ~40% of sites that had lower placebo responses, the suzetrigine arm within-group reduction in pain was similar to the overall study and had greater separation from the placebo arm. These analyses suggest that trial design innovation may better control the placebo response and separate the treatment effect of suzetrigine from placebo in future studies, which Vertex will incorporate as it designs the pivotal program.

Safety Results; Suzetrigine was generally well tolerated in the study. The incidence of adverse events (AEs) was 22.9% in the suzetrigine arm and 32.4% in the placebo arm. In both treatment arms, most AEs were mild to moderate. There were no serious adverse events (SAEs) related or possibly related to suzetrigine. There were no AEs leading to treatment discontinuation in patients treated with suzetrigine.

“Suzetrigine has again demonstrated its potential to fill an important unmet need in the treatment of pain. Today's LSR results are consistent with previous studies of this pain signal inhibitor in terms of showing a meaningful treatment effect across pain conditions and a favorable safety profile,” said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. “We did not see separation between the suzetrigine and the placebo arms. Yet our post-hoc analyses suggest that this could be due to the high placebo response in this study. We remain committed to studying LSR and innovating our Phase III study design to control for the placebo effect as we advance suzetrigine into pivotal development for this condition.”

“The suzetrigine Phase II  results clearly show reduced pain intensity from baseline in the active drug arm, and the potential for suzetrigine to fill an unmet need in relieving LSR pain, a heterogeneous condition that is notoriously difficult to treat,” said Christine Sang, M.D., M.P.H., FASA, Director, Translational Pain Research, Brigham and Women's Hospital, Associate Professor of Anesthesia, Harvard Medical School, co-chair of Vertex’s Peripheral Neuropathic Pain steering committee, and lead principal investigator on the study. “Managing the placebo response in pain trials is a complex challenge. We look forward to innovating in clinical trial design, including for the pivotal study, with the aim of bringing a potentially safe and effective treatment to patients suffering from LSR."

Next Steps for the Pain Portfolio: Neuropathic Pain - Vertex plans to advance suzetrigine into pivotal development for painful LSR following discussions with regulators on the study design and regulatory package. The company will apply learnings from analysis of the full Phase II data set and post-hoc analyses to inform the Phase III study design. Earlier this year, Vertex initiated its suzetrigine pivotal program in painful diabetic peripheral neuropathy (DPN), another type of peripheral neuropathic pain (PNP). That study is ongoing. Acute Pain - Additionally, as previously announced, suzetrigine is under FDA review for the treatment of moderate-to-severe acute pain. The agency granted priority review and assigned a Prescription Drug User Fee Act (PDUFA) target action date of January 30, 2025.

In line with its portfolio strategy, Vertex continues to advance preclinical and clinical development of additional NaV1.8 and NaV1.7 inhibitors, for use alone or in combination, in acute and neuropathic pain.

About the Phase II Suzetrigine Lumbosacral Radiculopathy (LSR) Study: This phase II, 12-week, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of suzetrigine in treating patients with painful LSR. A total of 218 patients were enrolled in the study and randomized 1:1 with suzetrigine or placebo. The primary endpoint was the within-group change from baseline in the weekly average of daily leg pain intensity on a numeric pain rating scale (NPRS) at Week 12. The study also included a placebo reference arm; however, the study was not designed nor powered for comparison between suzetrigine and placebo.

Secondary endpoints assessed the within-group change from baseline in the weekly average of the daily sleep interference scale at Week 12 and safety and tolerability. By blocking the pain signal from the peripheral sensory neurons, Vertex believes that suzetrigine may alleviate the suffering for millions of patients with painful LSR.