TRANQUILITY: Pacibekitug Reduces hs-CRP, Inflammatory Biomarkers in CKD

Pacibekitug, an investigational interleukin-6 (IL-6) antibody, substantially reduced inflammatory biomarkers in patients with chronic kidney disease (CKD) at high inflammatory risk during the phase 2 TRANQUILITY trial.¹

These data were presented at the European Society of Cardiology (ESC) Congress 2026 in Munich, Germany, by Deepak Bhatt, MD, MPH, MBA, director of Mount Sinai Fuster Heart Hospital and the Dr. Valentin Fuster Professor of Cardiovascular Medicine at the Icahn School of Medicine at Mount Sinai.¹

“Overall, in the context of a phase 2 trial, I would say it was a positive trial,” Bhatt told HCPLive in an exclusive interview. “Of course, the trial wasn’t powered for cardiovascular events. That’s what would need to come next: a phase 2 trial in the right population to see if this approach of targeting inflammation with IL-6 inhibition reduces adverse cardiovascular outcomes.”

TRANQUILITY was a randomized, double-blind, placebo-controlled study evaluating quarterly and monthly pacibekitug dosing among patients with CKD and elevated high-sensitivity C-reactive protein (hs-CRP). Patients were eligible if they were ≥18 years of age with a serum hs-CRP level of ≥2.0 mg/L and <15 mg/L, as well as a diagnosis of CKD. Patients with a history of immunodeficiency, gastrointestinal ulceration or perforation, or active diverticulitis, among other criteria, were excluded.²

Enrolled patients were randomly assigned in a 1:1:1:1 ratio to receive subcutaneous pacibekitug 25 or 50 mg every 90 days, 15 mg every 30 days, or placebo, all over 6 months. The primary endpoint was time-averaged percent change from baseline in hs-CRP through day 90. Secondary endpoints included the proportion of patients with time-averaged hs-CRP <2 mg/L at 90 days, time-averaged percent change in hs-CRP from baseline through day 180, and the safety and tolerability of pacibekitug, among others.^1,2

A total of 143 patients were included, with a mean age of 69 years. 72% of the enrolled patients received statins, and 59% had diabetes. By day 30, pacibekitug treatment had resulted in dose-dependent decreases in hs-CRP – these reductions were sustained through 180 days. Median time-averaged change in hs-CRP was +7% with placebo, -76% with pacibekitug 25 mg, -85% with 50 mg, and -89% with 15 mg (all P<.0001 vs. placebo). Additionally, Bhatt and colleagues noted substantial and sustained reductions in fibrinogen and Lp(a), as well as other inflammatory markers, across all 3 pacibekitug groups.¹

Ultimately, Bhatt and colleagues concluded that pacibekitug treatment efficaciously reduced hs-CRP in this patient population, with only 1.9% of patients discontinuing treatment and none reporting clear dose-related safety signals. However, Bhatt also acknowledges the lingering question of actual cardiovascular outcome improvements, given that the trial was not powered to examine this endpoint.¹

“Ongoing trials with other agents will see whether drugs specifically targeting Lp(a) and reducing Lp(a) are associated with cardiovascular benefit or not,” Bhatt said. “These results will be coming out, I imagine, relatively soon, likely before the end of the year. I think that the bolus of data that we’ll get in the next year or 2 about Lp(a) reduction strategies and whether they reduce cardiovascular events will tell us a lot.”

Editors’ Note: Bhatt reports disclosures with GSK, Merck, Cereno Scientific, Angiowave, Boehringer Ingelheim, Novo Nordisk, and others.

References

1. Bhatt D. TRANQUILITY: Efficacy of monthly and quarterly dosing of pacibekitug (IL-6 ligand mAb) targeting inflammation in CKD with high cardiovascular risk. Presented at the European Society of Cardiology (ESC) Congress 2026, Munich, Germany. August 28-31, 2026.

2. Tourmaline Bio. A Study to Evaluate TOUR006 in Patients With Chronic Kidney Disease and Elevated Hs-CRP (TRANQUILITY). ClinicalTrials.gov Identifier: NCT06362759. Updated August 11, 2026. Accessed September 4, 2026. https://clinicaltrials.gov/study/NCT06362759