Next Steps for Pacibekitug Following Positive TRANQUILITY Results

Pacibekitug outperformed placebo in reducing hs-CRP, Lp(a), and other inflammatory biomarkers in patients with chronic kidney disease (CKD) during the TRANQUILITY trial; however, without being powered for cardiovascular outcomes, the question of this drug’s efficacy in risk reduction still remains.¹

The data from TRANQUILITY 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. In an exclusive interview, HCPLive breaks down the results and investigators’ plans for a phase 3 trial of pacibekitug for cardiovascular events.¹

“This trial was meant to be a proof of principle, that the drug does what it’s supposed to – safely lowering hs-CRP in the context of a modest-size phase 2 trial,” Bhatt told HCPLive. “For the phase 3 trial planning, we were really never considering CKD because that’s a tough population. Things that have worked in other non-CKD populations for cardiovascular risk reduction haven’t always worked in advanced kidney disease.”

TRANQUILITY, a randomized, double-blind, placebo-controlled study evaluating pacibekitug administered quarterly and monthly to patients with CKD and elevated hs-CRP, enrolled patients with a serum hs-CRP level ≥2.0 mg/L and <15 mg/L and a diagnosis of CKD, among other criteria. These patients were randomly assigned in a 1:1:1:1 ratio to either pacibekitug 25 mg or 50 mg every 90 days, 15 mg every 30 days, or placebo.^1,2

The primary endpoint was time-averaged percent change from baseline in hs-CRP by day 90. Secondary endpoints included time-averaged percent change in hs-CRP through day 180, the proportion of patients with time-averaged hs-CRP <2 mg/L at 90 days, and the safety and tolerability of pacibekitug.²

A total of 143 patients were enrolled, of whom 72% were receiving statins and 59% had diabetes. Bhatt and colleagues noted dose-dependent reductions in hs-CRP by day 30, which were sustained through 180 days. The median time-averaged change was -76% with pacibekitug 25 mg, -85% with 50 mg, and -89% with 15 mg, compared to +7% with placebo. Fibrinogen and Lp(a) also saw sustained reductions in the pacibekitug arms, and no dose-related safety signals were recorded.¹

However, the trial itself was not powered to detect cardiovascular outcome improvements. Given the additional reductions in Lp(a), coupled with inflammation’s direct influence on cardiovascular disease risk, Bhatt believes that further data from ongoing trials will determine whether these targets are associated with cardiovascular benefit. On the other hand, inflammation is a notoriously narrow window to target – past trials, including CANTOS and ZEUS, have indicated the risk of increased fatal infection if inflammation is too significantly reduced and the lack of cardiovascular benefit if the effect is too small.

“The inflammation story is ongoing,” Bhatt said. “There are a number of trials in different therapeutic areas, and lots of different companies planning trials with various anti-inflammatory agents, phase 2 trials, phase 3 trials, ongoing in the planning stages. We’ll see whether that is also an independent axis of risk reduction. But for now, Lp(a) reduction, hs-CRP reduction, and a broader reduction of arterial inflammation all seem like promising approaches to study.”

Editor’s 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