Ruvonoflast (NT-0796), an oral NLRP3 inflammasome inhibitor developed by Boston-based Rezera Inc. (formerly NodThera), met its primary endpoint in the RESOLVE-1 Phase II trial, reducing high-sensitivity C-reactive protein (hsCRP) versus placebo over 24 weeks across a broad cardiometabolic population. The September 9 readout coincided with NodThera’s name change to Rezera and its announcement of plans to begin a Phase III registrational trial in peripheral artery disease (PAD) in the first half of 2027.
RESOLVE-1 enrolled 176 participants with and without type 2 diabetes, randomized to ruvonoflast 150 mg/day, 300 mg/day, or placebo for 24 weeks. Both active doses reduced hsCRP compared with placebo. Rezera said the reductions were consistent across participants regardless of diabetes status, and that baseline hsCRP elevation was not an inclusion criterion — meaning the signal emerged in an unenriched population. The company reported concordant reductions across multiple thrombo-inflammatory biomarkers, a dose-response relationship across the two doses tested, and no drug-related serious adverse events, no hepatotoxicity, and no increase in infections. Quantitative effect sizes have not yet been disclosed; full results are expected to be presented at a medical conference and submitted for publication in Q4 2026.
The RESOLVE-1 findings align with earlier published data from a smaller study in participants with elevated cardiovascular risk and high inflammatory burden, in which ruvonoflast reduced hsCRP by 82.2% from baseline versus 37.2% with placebo at four weeks — results published in the Journal of the American College of Cardiology in May 2026. Rezera said the combined dataset from more than 400 participants across five trials, with durations up to nine months and doses up to 450 mg/day, underpins the Phase III design. The company said it has reached regulatory alignment on endpoints, sample size, duration, and safety for the PAD study.
Ruvonoflast acts as an oral prodrug converted intracellularly to its active metabolite, which inhibits NLRP3 inflammasome assembly, blocking the upstream IL-1β/IL-6/IL-18 inflammatory cascade implicated in atherosclerotic cardiovascular disease. PAD, characterized by arterial narrowing that reduces limb blood flow, affects more than 230 million people globally and carries a two- to four-fold elevated risk of cardiovascular death depending on disease stage, according to Rezera.