Pacibekitug, an investigational long-acting monoclonal antibody targeting interleukin-6 (IL-6), produced sustained reductions in inflammatory biomarkers in patients with chronic kidney disease (CKD) at high inflammatory risk, according to results from the phase 2 TRANQUILITY trial presented in a Hot Line session at the European Society of Cardiology (ESC) Congress 2026 in Munich, Germany.¹
Addressing hypertension, smoking, diabetes, elevated cholesterol, and obesity reduces cardiovascular risk, but these factors account for only around half of the global cardiovascular disease burden.² Despite standard therapies, about 30% of patients with atherosclerotic cardiovascular disease, and approximately 40% of those with concomitant CKD, remain at high inflammatory risk based on elevated high-sensitivity C-reactive protein (hs-CRP).³
Frequently Asked Questions
Pacibekitug is an investigational long-acting monoclonal antibody targeting interleukin-6 (IL-6), a mediator of inflammation linked to cardiovascular risk.
What did the TRANQUILITY trial find?
Pacibekitug produced dose-dependent, sustained reductions in hs-CRP through 180 days in patients with CKD and elevated inflammatory risk, with the largest reduction (-89%) seen with 15 mg every 30 days.
Is pacibekitug proven to reduce cardiovascular events?
TRANQUILITY was a phase 2 biomarker trial; a larger phase 3 trial is needed to determine whether the inflammatory reductions translate into fewer cardiovascular events.
“A growing body of genetic, epidemiological and clinical evidence suggests that IL-6 mediates a key inflammatory pathway linked to cardiovascular risk,” Deepak Bhatt, MD, MPH, Icahn School of Medicine at Mount Sinai. “We evaluated the long-acting monoclonal antibody against IL-6, pacibekitug, in patients with chronic kidney disease and elevated levels of hs-CRP in the TRANQUILITY trial.”
Pacibekitug Efficacy and TRANQUILITY Trial Design
TRANQUILITY was a placebo-controlled phase 2 trial conducted at 49 centers in the US.¹ Investigators enrolled 143 patients with CKD stage 3-4 and elevated hs-CRP, defined as 2 to < 15 mg/L and randomly assigned them in a 1:1:1:1 ratio to subcutaneous pacibekitug 25 mg or 50 mg every 90 days, 15 mg every 30 days, or placebo, for 6 months.¹ The study population had a mean age of 69 years, 64% were female, 72% received statins, and 59% had diabetes.¹
Results showed pacibekitug produced dose-dependent decreases in hs-CRP by day 30, sustained through day 180. Median time-averaged change from baseline in hs-CRP through day 180 was +7% with placebo, compared with -76% with pacibekitug 25 mg every 90 days, -85% with pacibekitug 50 mg every 90 days, and -89% with pacibekitug 15 mg every 30 days (all P <.0001 vs placebo). Sustained reductions in other inflammatory markers, along with fibrinogen and lipoprotein(a), were also observed across pacibekitug groups compared with placebo.¹
Pacibekitug Safety and Cardiovascular Inflammation Landscape
Pacibekitug was well tolerated, with few discontinuations (1.9%) and no clear dose-related safety signals identified.¹
“Results from the TRANQUILITY study demonstrate that the IL-6 pathway can be durably suppressed with infrequent dosing and no new safety signals,” Bhatt said. “The next step is to determine whether the biomarker effects observed in TRANQUILITY translate into improved cardiovascular outcomes for patients in a larger, longer-term phase III trial.”
Pacibekitug joins a growing class of IL-6-targeted antibodies in cardiovascular development, following a similar trajectory to ziltivekimab, whose phase 2 RESCUE trial showed comparable hs-CRP reductions in an overlapping CKD population and is now being tested for cardiovascular outcomes in the ongoing phase 3 ZEUS trial.⁴
Earlier proof-of-concept for anti-inflammatory cardiovascular risk reduction came from CANTOS, in which the IL-1beta inhibitor canakinumab reduced cardiovascular events, though it was ultimately not pursued for cardiovascular indications.⁴ Together, these programs reflect a broader effort to establish IL-6 and IL-1beta inhibition as viable strategies for residual inflammatory cardiovascular risk beyond lipid- and blood pressure-lowering therapy.
References
European Society of Cardiology. Sustained reductions in inflammatory markers seen with novel antibody drug. Published August 29, 2026. Accessed August 29, 2026.
Global Cardiovascular Risk Consortium. Global effect of cardiovascular risk factors on lifetime estimates. N Engl J Med. 2025;393:125-138.
Navar AM, Bai L, Højen JF, et al. Global prevalence of elevated high-sensitivity C-reactive protein in patients with atherosclerotic cardiovascular disease, with and without chronic kidney disease: findings from the POSEIDON study. Atherosclerosis. 2026;419. doi:10.1016/j.atherosclerosis.2026.120816
Ridker PM. From RESCUE to ZEUS: will interleukin-6 inhibition with ziltivekimab prove effective for cardiovascular event reduction? Cardiovasc Res. 2021;117(11):e138-e140. doi:10.1093/cvr/cvab231
