Rezera’s ruvonoflast met the primary hsCRP endpoint in Phase 2 RESOLVE-1, supporting a Phase 3 peripheral artery disease trial planned for 2027.
Written By: Khushi Patel, PharmD
Reviewed By: Pharmacally Editorial Team
Rezera’s oral NLRP3 inhibitor ruvonoflast reduced systemic inflammation in the Phase 2 RESOLVE-1 trial (NCT07055516) across participants with and without type 2 diabetes, meeting the study’s primary hsCRP endpoint through week 24. Rezera has aligned with regulatory agencies on core elements of a Phase 3 peripheral artery disease (PAD) program, which it expects to initiate in the first half of 2027.
Ruvonoflast Reduces hsCRP Over 24 Weeks
The RESOLVE-1 study evaluated ruvonoflast across 176 participants with and without type 2 diabetes. The trial met its primary endpoint assessing change from baseline in high-sensitivity C-reactive protein (hsCRP) through week 24. Both the 150 mg once-daily and 150 mg twice-daily regimens (300 mg total daily dose) demonstrated statistically significant hsCRP reductions compared to placebo.
Significantly, elevated baseline hsCRP was not an enrollment requirement. Biomarker reductions occurred consistently across participants with and without type 2 diabetes, extending the drug’s anti-inflammatory signal beyond populations selected solely for high baseline inflammatory burden.
Ruvonoflast also demonstrated concordant reductions across multiple downstream thrombo-inflammatory biomarkers, confirming dose-dependent engagement of the NLRP3 pathway. Treatment had no impact on body weight.
Upstream NLRP3 Inhibition in Peripheral Artery Disease
Ruvonoflast is an oral, tissue-penetrant inhibitor of the NLRP3 inflammasome an intracellular sensor controlling the activation of interleukin-1β (IL-1β) and IL-18. These key cytokines drive downstream inflammatory signaling, including pathways linked to IL-6 and CRP. Blocking NLRP3 provides an upstream strategy to modulate chronic inflammation driving cardiometabolic disease.
PAD is a major manifestation of atherosclerotic cardiovascular disease wherein narrowed peripheral arteries restrict arterial blood flow, primarily to the lower extremities. This leads to impaired walking capacity, reduced functional freedom, and elevated major adverse cardiovascular and limb events. Affecting more than 230 million people worldwide, PAD represents a high unmet medical need.
The RESOLVE-1 findings build upon earlier Phase 1b data where 28 days of ruvonoflast treatment produced an 82.2% reduction in hsCRP versus 37.2% with placebo in high-risk patients. RESOLVE-1 extends these observations over a longer 24-week treatment period in a broader, unselected population.
Safety Profile Supports Phase 3 Advancement
Ruvonoflast was well tolerated across all treatment groups. Key safety findings showed:
- No evidence of drug-related liver toxicity
- No increase in overall infections or serious infections
- Zero drug-related serious adverse events (SAEs)
To date, more than 400 participants across five clinical trials have received ruvonoflast at daily doses ranging from 150 mg to 450 mg, with exposure durations reaching up to nine months.
Phase 3 Program Targeted for H1 2027
Following regulatory alignment on core trial parameters including primary endpoints, sample size, study duration, and safety monitoring Rezera expects to initiate its Phase 3 PAD study in H1 2027.
“The RESOLVE-1 findings establish dose-dependent clinical efficacy across a broad cardiometabolic cohort and provide strong validation for advancing ruvonoflast into Phase 3 development,” said Jyothis George, Chief Medical Officer at Rezera.
Marc Bonaca, Executive Director of the Colorado Prevention Center and Professor of Medicine at the University of Colorado Anschutz, noted that targeting NLRP3 directly addresses residual inflammatory pathways that remain under-treated in PAD care.
Rezera plans to present detailed findings from RESOLVE-1 at an upcoming medical conference in Q4 2026 and submit the full manuscript for peer-reviewed publication.
Reference
Rezera Announces Ruvonoflast Met its Primary Inflammation Endpoint and Demonstrated Favorable Safety Profile in RESOLVE-1 Phase 2 Clinical Trial, Rezera, 09 September 2026
About the Writer
Khushi Patel is a PharmD (Linkedin) professional with a strong foundation in clinical pharmacy, patient-centered care, regulatory affairs, and pharmacovigilance, with published work on Brugada syndrome.
Her interests include regulatory affairs, pharmacovigilance, guideline integration, multimodal therapy, pharmacogenomics, and antibiogram utilization, with a focus on evidence-based clinical decision-making and medication safety.
As a Pharmacally healthcare writer, she translates clinical and scientific evidence into clear, accurate, and clinically relevant healthcare content, while continuously developing her expertise in evolving pharmacy practice.