© 2024 MJH Life Sciences™ and Patient Care Online. All rights reserved.
Vertex Nonopioid Analgesic on Par with Placebo in Phase 2 Study of Lumbosacral Radiculopathy
Pain relief with suzetrigine was comparable to that seen with placebo, an issue Vertex plans to address with study design as the drug moves to the pivotal phase 3 trials.
Boston-based Vertex announced this morning that its phase 2 trial of suzetrigine, the novel highly selective NaV1.8 pain signal inhibitor, showed pain relief comparable to that from placebo in adults with lumbosacral radiculopathy (LSR), the chronic lower back condition. The equivocal findings for use of the analgesic for chronic pain come as the company anticipates a FDA PDUFA date of January 30, 2025, for approval of suzetrigine for treatment of acute pain.
Treatment with suzetrigine met the study’s primary endpoint with a statistically significant and clinically meaningful 2.02-point within-group reduction from baseline in the weekly average of daily leg pain intensity on the Numeric Pain Rating Scale (NPRS), where 0 = no pain and 10 = worst pain imaginable, Vertex said in a news release. For participants in the placebo arm, the reduction in pain from baseline as measured on the NPRS was similar at the 12-week study visit, at 1.98 points. According to Vertex, the study was not designed or powered for a statistical comparison between the active drug and placebo groups.
In post-hoc analyses of the findings on suzetrigine efficacy, Vertex reported variability in pain reduction in placebo groups across study sites, an issue “recognized” in pain trials, the company said. At approximately 40% of study sites where placebo responses were lower, the within-group reduction in pain in the suzetrigine arm was comparable to the overall study results.
“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 [p]hase 3 study design to control for the placebo effect as we advance suzetrigine into pivotal development for this condition,” Carmen Bozic, MD, Vertex EVP, global medicines development and medical affairs and chief medical officer said in the news release, addressing the apparent shortfalls.
Based on the phase 2 results, the potential for suzetrigine to address an unmet need in treatment for LSR-related pain remains, according to Christine Sang, MD, MPH, who describes LSR as “a heterogenous condition that is notoriously hard to treat.” Sang also points to the challenge of managing the placebo response in pain trials and anticipates working with regulators to revise the design of the pivotal phase 3 trial now planned. Sang is director of translational pain research at Brigham and Women's Hospital, associate professor of anesthesia at Harvard Medical School, and also co-chair of Vertex’s peripheral neuropathic pain steering committee, according to the news release. The study design will be a topic of discussion during a conference call and webcast scheduled for early today.
The 218 adults with painful LSR in the phase 2, 12-week, randomized, double-blind, placebo-controlled study were randomly assigned treatment with suzetrigine or placebo. The primary endpoint was the within-group change from baseline in the weekly average of daily leg pain intensity on the NPRS at week 12.
Findings for the secondary endpoints were not reported in the release but included assessments of the within-group change from baseline in weekly average of the score on a daily sleep interference scale, also at week 12.
The safety assessment showed that suzetrigine was well tolerated. The adverse event (AE) rate was 22.9% in the suzetrigine-treated group and 32.4% among study participants treated with placebo. None led to treatment discontinuation among those treated with the active drug and Vertex reported no serious AEs.
As announced earlier this year, suzetrigine is currently under FDA review for the treatment of moderate-to-severe acute pain. The regulator granted the drug priority review and assigned a Prescription Drug User Fee Act target action date of January 30, 2025.
Vertex is also advancing suzetrigine through a pivotal trial program in painful diabetic peripheral neuropathy.
