MUNICH — Researchers presented results from the phase 2 TRANQUILITY clinical trial on August 29, 2026, showing that pacibekitug achieved durable suppression of inflammatory markers in patients with chronic kidney disease and elevated cardiovascular risk. The data were delivered during a Hot Line Session at the European Society of Cardiology Congress (ESC 2026) in Munich, Germany.

The TRANQUILITY phase 2 clinical trial evaluated the safety and efficacy of pacibekitug, an investigational anti-interleukin-6 monoclonal antibody. Pacibekitug is a long-acting monoclonal antibody designed to target interleukin-6 (IL-6), a signaling protein involved in inflammatory pathways associated with cardiovascular risk. Tourmaline Bio, Inc. a Novartis company, sponsored the trial.

The study was a randomized, double-blind, placebo-controlled trial conducted at 49 centers in the U.S. It enrolled 143 adults with chronic kidney disease (stage 3–4) and elevated high-sensitivity C-reactive protein (hsCRP) levels between 2 and less than 15 mg/L. Participants were randomized in a 1:1:1:1 ratio to receive placebo, pacibekitug 25 mg every 90 days, pacibekitug 50 mg every 90 days, or pacibekitug 15 mg every 30 days for 180 days.

Deepak L. Bhatt, MD, MPH, Director of Mount Sinai Fuster Heart Hospital and Dr. Valentin Fuster Professor of Medicine at the Icahn School of Medicine at Mount Sinai, presented the results. Dr. Bhatt chaired the Scientific Advisory Board for Tourmaline Bio and receives research funding from Novartis for this trial.

The TRANQUILITY trial's primary endpoint was the median time-averaged percent change in hs-CRP through Day 90, with 86% and 85% reductions in the 50 mg Q90D and 15 mg Q30D groups, respectively. On day 180, time-averaged hsCRP reductions ranged from 76% to 89% across pacibekitug treatment groups, compared with a 7% increase in the placebo group. Median time-averaged change from baseline in hsCRP through day 180 was plus 7% with placebo, minus 76% with pacibekitug 25 mg every 90 days, minus 85% with pacibekitug 50 mg every 90 days, and minus 89% with pacibekitug 15 mg every 30 days (all p less than 0.0001 vs. placebo).

Pacibekitug treatment resulted in dose-dependent decreases in hsCRP by day 30, which were sustained to day 180. Additionally, 77%-88% of participants receiving pacibekitug achieved hs-CRP levels less than 2 mg/L, and 45%-65% achieved less than 1 mg/L by day 180, compared to 15% in the placebo group. Sustained reductions in other inflammatory markers, as well as fibrinogen and lipoprotein(a), were observed across pacibekitug groups versus placebo. Pacibekitug was generally well tolerated, with few discontinuations (1.9%) and no new safety signals identified.

"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. He added, "These findings demonstrate that durable suppression of the IL-6 pathway is achievable with infrequent dosing of a long-acting monoclonal antibody."

Why It Matters

"The next critical step is to determine whether the effects observed in TRANQUILITY translate into improved cardiovascular outcomes in patients with elevated inflammatory cardiovascular risk," Bhatt said. He also stated, "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."

Timeline

On August 29, 2026, results from the TRANQUILITY trial were presented in a Hot Line Session at the European Society of Cardiology Congress (ESC 2026) in Munich, Germany.

He said the results demonstrate that the IL-6 pathway can be durably suppressed with infrequent dosing and no new safety signals. He 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. He also said the next critical step is to determine whether the effects observed in TRANQUILITY translate into improved cardiovascular outcomes in patients with elevated inflammatory cardiovascular risk. He said these findings demonstrate that durable suppression of the IL-6 pathway is achievable with infrequent dosing of a long-acting monoclonal antibody. The median time-averaged change from baseline in hsCRP through day 180 was +7% with placebo, −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<0.0001 vs. placebo).

What's New

Pacibekitug demonstrated no new safety signals, with only 1.9% of participants discontinuing the trial, according to the TRANQUILITY study protocol. Around 30% of patients with atherosclerotic cardiovascular disease and around 40% of those with concomitant chronic kidney disease are at high inflammatory risk based on elevated hs-CRP levels.

The next phase III trial for pacibekitug will be powered to evaluate cardiovascular outcomes, as stated by Dr. Bhatt following the TRANQUILITY results. He also said results from the TRANQUILITY study demonstrate that the IL-6 pathway can be durably suppressed with infrequent dosing and no new safety signals.

How Sources Differ

Regarding the tranquility study, Deepak Bhatt said the results demonstrate that the IL-6 pathway can be durably suppressed with infrequent dosing and no new safety signals.

Regarding improved cardiovascular outcomes, Deepak L. Bhatt said the next critical step is to determine whether the effects observed in TRANQUILITY translate into improved cardiovascular outcomes in patients with elevated inflammatory cardiovascular risk.

Regarding chronic kidney disease, the TRANQUILITY phase 2 clinical trial participant demographics report stated that the study enrolled 143 adults with chronic kidney disease (stage 3–4) and elevated high-sensitivity C-reactive protein (hsCRP) levels between 2 and less than 15 mg/L. Epidemiological data on cardiovascular disease and inflammation indicated that around 30% of patients with atherosclerotic cardiovascular disease and around 40% of those with concomitant chronic kidney disease are at high inflammatory risk based on elevated hs-CRP levels.