Rezera reports statistically significant additional hsCRP reductions with ruvonoflast plus semaglutide in the Phase 2 RESOLVE-2 trial.
Written By: Aasritha Thippavajjala, PharmD
Reviewed By: Pharmacally Editorial Team
Rezera Inc., a clinical-stage biotechnology company based in Boston, announced topline results from the Phase 2a RESOLVE-2 clinical trial on October 7, 2026. The randomized study evaluated ruvonoflast, formerly known as NT-0796, as an adjunct to semaglutide in adults with obesity.
The 82-participant trial was primarily designed to evaluate the safety and tolerability of the combination, while also assessing exploratory effects on inflammatory markers and weight. Rezera reported that participants receiving ruvonoflast plus semaglutide achieved statistically significant additional reductions in hsCRP compared with those receiving semaglutide alone, with the difference maintained throughout the study.
Study Design, Population and Dosing
RESOLVE-2 (NCT07220629) was a randomized, double-blind, placebo-controlled, parallel-group, multicenter Phase 2a study evaluating the safety, tolerability and exploratory effects of ruvonoflast when added to semaglutide.
A total of 82 adults with obesity were randomized 1:1 to receive oral ruvonoflast or matching placebo for 32 weeks. All participants received once-weekly subcutaneous semaglutide, which was titrated according to the approved U.S. prescribing information to a dose of up to 2.4 mg.
Safety and tolerability were the primary objectives of the study. Baseline hsCRP concentration was not an inclusion criterion.
Ruvonoflast Produced Additional hsCRP Reductions
Ruvonoflast added to semaglutide produced statistically significant additional reductions in hsCRP compared with semaglutide alone. According to Rezera, the separation between the treatment groups was maintained throughout the study.
Weight loss was comparable between the two treatment groups in the overall study population. The findings therefore indicate an additional effect on the inflammatory marker rather than a reported difference in overall weight reduction between the treatment groups.
Because RESOLVE-2 was primarily designed to assess safety and tolerability, the hsCRP findings should be considered within the exploratory clinical objectives of the study rather than interpreted as evidence of a demonstrated cardiovascular outcome benefit.
Safety and Tolerability
Ruvonoflast was generally well tolerated when administered with semaglutide, according to Rezera. The company reported that the safety profile was consistent with previous clinical experience with ruvonoflast and the known safety profile of semaglutide.
No new safety signals or meaningful imbalances in safety parameters were reported.
These findings provide additional clinical safety information as Rezera advances ruvonoflast into further development, although larger and longer studies will be required to characterize its safety profile more fully.
Findings in Participants with Elevated Baseline hsCRP
Rezera also reported a subgroup analysis among participants whose baseline hsCRP concentration was at least 2 mg/L.
In this subgroup, participants receiving ruvonoflast plus semaglutide were more than twice as likely to achieve an hsCRP concentration below 2 mg/L compared with those receiving semaglutide alone.
The company linked the 2 mg/L threshold to elevated residual inflammatory risk in cardiovascular disease. However, the RESOLVE-2 findings do not establish that reducing hsCRP with ruvonoflast will translate into fewer cardiovascular events.
Previous Anti-Inflammatory Data and PAD Rationale
Earlier clinical data have supported the anti-inflammatory activity of ruvonoflast, including an 82% reduction in hsCRP alongside decreases in IL-6, IL-18 and fibrinogen. These findings came from earlier clinical studies and were not outcomes of RESOLVE-2.
Dr. Marc Bonaca of the University of Colorado Anschutz said the additive reductions in inflammatory markers observed with ruvonoflast and semaglutide are encouraging for further development in peripheral artery disease (PAD). He also referenced the STRIDE trial, in which semaglutide improved walking distance in patients with PAD and diabetes, although the contribution of its anti-inflammatory effects to this outcome remains a mechanistic hypothesis.
Next Steps and Investigational Status
Rezera is advancing ruvonoflast in PAD, including through the REVEAL-PAD study, and plans to progress toward a Phase 3 program. While RESOLVE-2 was conducted in adults with obesity rather than patients with PAD, its inflammatory findings may support further evaluation of ruvonoflast in cardiovascular disease.
Rezera plans to present the RESOLVE-2 findings at an upcoming medical conference and submit the data for peer-reviewed publication. The company will also present Phase 2 RESOLVE-1 data in participants with elevated cardiometabolic risk as a late-breaking Featured Science presentation at the American Heart Association Scientific Sessions in Chicago from November 6–9, 2026.
Ruvonoflast remains an investigational, unapproved therapy, and further clinical studies are needed to determine whether reductions in hsCRP translate into meaningful clinical benefits.
Reference
Rezera Announces Positive RESOLVE-2 Phase 2 Clinical Trial Results Demonstrating Favorable Safety and Tolerability Profile for Ruvonoflast in Combination with Semaglutide, Rezera, 07 October 2026
Study to Explore the Safety and Efficacy of NT-0796 as an Adjunct to Semaglutide in Participants with Obesity (RESOLVE-2) (RESOLVE-2), ClinicalTrials.gov ID NCT07220629
About the Writer
Aasritha Thippavajjala (Linkedin) is a pharm D student and aspiring medical writer with medical writing, clinical training experience and a strong interest in clinical research and patient safety She has hands-on exposure to clinical pharmacy activities including medication profile assessment, clinical case review, identification of potential drug-related problems, ADR awareness, patient counselling, and clinical documentation. She has also gained experience in medical literature review, evidence synthesis, and scientific communication through her published review article on digital twin-based patient simulation and her poster presentation at the 74th Indian Pharmaceutical Congress. Certified in ICH Good Clinical Practice (E6(R3)) and Scientific Writing in Health Research, she is passionate about applying her clinical knowledge and research skills to medical writing ,clinical research and contributing to accurate, evidence-based healthcare.