TRANQUILITY: Pacibekitug Safely Lowers hs-CRP in ASCVD, With Deepak Bhatt, MD

The interleukin-6 (IL-6) inhibitor pacibekitug (TOUR006) has indicated its safety and efficacy in reducing high-sensitivity C-reactive protein (hs-CRP) levels in patients with chronic kidney disease (CKD) and atherosclerotic cardiovascular disease (ASCVD), based on results from the phase 2 TRANQUILITY trial.1

These data were presented at the American Heart Association’s Scientific Sessions 2025 in New Orleans, Louisiana, by Deepak Bhatt, MD, director of the Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai.1

Pacibekitug is an investigational long-acting fully human monoclonal antibody against the IL-6 cytokine, in development by Tourmaline Bio. While the TRANQUILITY trial investigated its efficacy in treating ASCVD, pacibekitug is also under development for thyroid eye disease, with plans to expand into abdominal aortic aneurysm in the future.2

“We showed incremental benefit in hs-CRP reduction, and hopefully that will translate into cardiovascular event reduction,” Bhatt said in an exclusive interview with HCPLive. “But this wasn’t a trial designed to measure cardiovascular events. TRANQUILITY was designed to look at safety and to look at hs-CRP, and it seemed to be safe and highly efficacious in reducing risk.”

Patients were included in the TRANQUILITY trial if they were ≥18 years old, had a serum hs-CRP level ≥2.0 mg/L and <15 mg/L, and a diagnosis of CKD. Patients were excluded if they exhibited evidence of active infection, had serious infections within 6 months or >1 episode within 18 months, a known history of immunodeficiency, a history of gastrointestinal ulceration or perforation within 12 months, a history of active diverticulitis, inflammatory bowel disease, or GI abscess within 12 months, among other criteria.3

The treatment period lasted 6 months, followed by a follow-up period of an additional 6 months. The primary endpoint was median time-averaged percent change in hs-CRP through day 90, adjusting for baseline. The key secondary endpoint was the percentage of participants achieving time-averaged hs-CRP below 2 mg/L through day 90. Additionally, investigators noted the percentage of participants achieving hs-CRP reductions of ≥50%.2

Bhatt and colleagues ultimately included 143 patients, stratifying them by CKD stage and randomly assigning them to receive either pacibekitug 25 mg quarterly, 50 mg quarterly, or 15 mg monthly, or placebo, all delivered subcutaneously. Median age was 71 years, and 62% of patients were women. Baseline estimated glomerular filtration rate and hs-CRP were 43 ml/min/1.73m2 and 4.45 mg/L, respectively.1

By day 90, the median time-averaged percent reduction in hs-CRP was 86% for the 50 mg dose, 75% for the 25 mg dose, and 85% for the 15 mg dose, versus 15% for the placebo arm (all P <.0001). Several patients achieved hs-CRP reductions ≥50%, and the percentage of patients with hs-CRP <1 mg/L at day 90 was 60%, 45%, and 65% for the 50 mg, 25 mg, and 15 mg arms compared to 13% for placebo (all P <.0001).1

Bhatt and colleagues concluded that hs-CRP was reduced significantly across all prespecified groups with pacibekitug. They also observed significant reductions in serum amyloid A, fibrinogen, and lipoprotein(a). The incidence of adverse events was 54% and 56% in the pooled pacibekitug and placebo arms, respectively. The team noted similar findings for serious adverse events (10% vs 11%), infections (24% vs 22%), and serious infections (4% vs 3%). According to the study abstract, pacibekitug is now the first IL-6 inhibitor to demonstrate sustained and significant reductions in hs-CRP with quarterly dosing.1

“Our hope is that, on the basis of the TRANQUILITY trial, there will be a phase 3 trial powered to look at cardiovascular end points,” Bhatt said. “That’s really what the purpose of the TRANQUILITY trial was: to see if it looked like the drug was safe, if it looked like there was an advantage potential over other IL-6 inhibitors, and to proceed with phase 3 testing.”

References

1. Pergola P, Szarek M, Zayed H, et al. A Phase 2 Multicenter, Randomized Double-Blind, Placebo-Controlled Study of Monthly or Quarterly Subcutaneous Administration of the Interleukin-6 Inhibitor Pacibekitug in Patients With Elevated High-Sensitivity C-Reactive Protein and Chronic Kidney Disease: 90-Day Analyses from TRANQUILITY. Abstract presented at the American Heart Association’s Scientific Sessions 2025. New Orleans, Louisiana. November 8-10, 2025.

2. Tourmaline Bio, Inc. A Study to Evaluate TOUR006 in Patients With Chronic Kidney Disease and Elevated Hs-CRP (TRANQUILITY). ClinicalTrials.gov Identifier: NCT06362759. Updated November 14, 2025. Accessed November 20, 2025. https://clinicaltrials.gov/study/NCT06362759

3. Mishek S. Tourmaline Bio Announces Positive Topline Results from the Ongoing Phase 2 TRANQUILITY Trial Evaluating Pacibekitug in Patients with Elevated High-Sensitivity C-reactive Protein and Chronic Kidney Disease. Tourmaline Bio. May 20, 2025. Accessed November 20, 2025. https://ir.tourmalinebio.com/news-releases/news-release-details/tourmaline-bio-announces-positive-topline-results-ongoing-phase