Rezera's Oral NLRP3 Inhibitor Ruvonoflast Hits Primary Inflammation Endpoint in Phase 2 RESOLVE-1, Phase 3 PAD Trial Planned for 2027
核心洞察
Rezera (搜索)'s oral NLRP3 (搜索) inhibitor ruvonoflast (搜索) met the primary endpoint of change in hsCRP up to week 24 in the Phase 2 RESOLVE-1 trial.
Both the 150 mg daily and 300 mg daily doses reduced hsCRP versus placebo in participants with and without type 2 diabetes (搜索).
The company reported no drug-related serious adverse events, no hepatotoxicity and no increase in infections across treatment groups.
Rezera (搜索) Inc. reported that ruvonoflast (搜索), its oral NLRP3 (搜索) inflammasome inhibitor, met the primary inflammation endpoint in the Phase 2 RESOLVE-1 trial, reducing high-sensitivity C-reactive protein (hsCRP) versus placebo over 24 weeks in a broad cardiometabolic population. The September 9 readout coincided with the Boston-based company's rebranding from NodThera (搜索) to Rezera and its announcement that it plans to begin a Phase 3 registrational trial in peripheral artery disease (搜索) (PAD) in the first half of 2027.
RESOLVE-1 Design and Endpoint
RESOLVE-1 (NCT07055516) was a multi-center, randomized, double-blind, placebo-controlled Phase 2 trial evaluating the efficacy, safety and pharmacodynamic effects of ruvonoflast (搜索) in participants with and without type 2 diabetes (搜索). The study enrolled 176 participants randomized to ruvonoflast 150 mg/day or 300 mg/day, or placebo, in addition to standard of care, for a 24-week treatment period. The primary endpoint was change from baseline in hsCRP up to week 24, assessed as a measure of residual inflammatory risk. Baseline hsCRP was not an inclusion criterion, meaning the trial was not enriched for participants with elevated inflammatory burden.
Both active doses reduced hsCRP compared with placebo, with reductions observed in participants with and without type 2 diabetes (搜索). Rezera (搜索) said the findings demonstrate a clear dose-response for ruvonoflast (搜索) and provide a foundation for Phase 3 trials using doses of up to 450 mg/day. Quantitative effect sizes from RESOLVE-1 have not yet been disclosed; full results are expected to be presented at an upcoming medical conference and submitted for publication in the fourth quarter of 2026.
Biomarker and Safety Findings
Beyond hsCRP, treatment with ruvonoflast (搜索) produced concordant reductions across multiple thrombo-inflammatory biomarkers, which the company characterized as broad, dose-dependent engagement across the NLRP3 (搜索) inflammatory axis. There was no impact on body weight. Ruvonoflast was generally well tolerated across all treatment groups. Analysis of safety data revealed no evidence of liver toxicity caused by ruvonoflast, no increase in infections or serious infections, and no drug-related serious adverse events.
"The RESOLVE-1 results are a key milestone in the development of ruvonoflast (搜索), establishing dose-dependent clinical effects in a broad cardiometabolic patient population and demonstrating a favourable safety profile that supports advancement of this unique NLRP3 (搜索) inhibitor into Phase 3," said Dr. Jyothis George, MBBS, Ph.D., Chief Medical Officer at Rezera (搜索). "These data are consistent with our recent peer-reviewed publication in study participants with elevated cardiovascular risk. We look forward to advancing ruvonoflast into a Phase 3 study in participants with PAD, where the unmet need is high."
Consistency With Prior Data
The RESOLVE-1 results align with previously published data from a smaller study in participants with elevated cardiovascular risk and high inflammatory burden, in which ruvonoflast (搜索) reduced hsCRP by 82.2% from baseline versus 37.2% with placebo at four weeks. Those results were published in the Journal of the American College of Cardiology in May 2026. Rezera (搜索) said the combined dataset — more than 400 participants across five ruvonoflast clinical trials, with durations of up to nine months and doses ranging from 150 mg/day to 450 mg/day — underpins the Phase 3 design.
Ruvonoflast (搜索) (formerly NT-0796) acts as an oral prodrug converted intracellularly to its active metabolite, which inhibits NLRP3 (搜索) inflammasome assembly, blocking the upstream IL-1β/IL-6/IL-18 inflammatory cascade implicated in atherosclerotic cardiovascular disease (搜索). The company's lead program recently completed both the Phase 2 RESOLVE-1 and RESOLVE-2 trials; RESOLVE-2 is evaluating ruvonoflast as an adjunct to semaglutide in obesity (搜索) and is active but not recruiting.
Phase 3 PAD Program
Rezera (搜索) said it has aligned with regulators on core elements of the Phase 3 PAD trial design, including endpoints, sample size, duration and safety, and plans to initiate the study in the first half of 2027. PAD, characterized by arterial narrowing that reduces limb blood flow, affects more than 230 million people worldwide and carries a two- to four-fold elevated risk of cardiovascular death depending on disease stage, according to Rezera.
"Ruvonoflast (搜索) has demonstrated significant reductions in multiple measures of inflammation, a core driver of disease in PAD, giving us a potential novel therapeutic approach for a disease with great unmet need," said Marc Bonaca, M.D., M.P.H., Executive Director of the Colorado Prevention Center, Professor of Medicine at the University of Colorado Anschutz, and Chair of the American Heart Association's PAD Collaborative. "Peripheral artery disease (搜索) affects more than 230 million people worldwide, yet the treatments we have still don't adequately address one of the core axes of risk and drivers of the disease. I'm excited about the prospect of a new treatment for patients in a field that has lagged in innovation relative to other areas of cardiovascular medicine. The upstream targeting of the NLRP3 (搜索) pathway with ruvonoflast, a highly tissue penetrant molecule, could address PAD in a way that the current standard of care simply doesn't reach."
Competitive Landscape and Pipeline
The NLRP3 (搜索) inhibitor field has attracted multiple programs, though none has yet reached approval in cardiovascular disease. Novartis's Ilaris (canakinumab), an injectable IL-1β antibody, demonstrated cardiovascular event reduction in the CANTOS trial but was not developed commercially for that indication. Smaller-molecule NLRP3 inhibitors from companies including Inflazome (搜索) (acquired by Roche) and IFM Therapeutics (搜索) have been in earlier development. Rezera (搜索)'s oral, tissue-penetrant formulation and the duration of its clinical dataset — including RESOLVE-1's 24-week treatment window — distinguish its program, though cross-trial comparisons remain limited without published numerical data from RESOLVE-1.
Rezera (搜索) is also advancing trabzanoflast (搜索) (formerly NT-0150) for the treatment of neurologic diseases, with Phase 1 topline results expected in the fourth quarter of 2026. The company maintains headquarters in Boston, Massachusetts, with an R&D base in Cambridge, UK.