Pacibekitug is an investigational monoclonal antibody developed by Tourmaline Bio, Inc., through a license form

Pfizer Pfizer Inc. ( ) is an American Multinational corporation, multinational Pharmaceutical industry, pharmaceutical and biotechnology corporation headquartered at The Spiral (New York City), The Spiral in Manhattan, New York City. Founded in 184 ...

, targeting

interleukin-6 Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smoo ...

(IL-6) for the treatment of inflammatory conditions. It is administered subcutaneously and is designed to reduce systemic inflammation by inhibiting IL-6, a pro-inflammatory

cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

implicated in various diseases, including

cardiovascular disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...

and

chronic kidney disease Chronic kidney disease (CKD) is a type of long-term kidney disease, defined by the sustained presence of abnormal kidney function and/or abnormal kidney structure. To meet criteria for CKD, the abnormalities must be present for at least three mo ...

(CKD). Pacibekitug is notable for its potential for quarterly dosing, offering a less frequent administration schedule compared to other IL-6 inhibitors. As of May 2025, it is in phase 2 clinical trials, with results demonstrating significant reductions in high-sensitivity C-reactive protein (hsCRP) in CKD patients with elevated inflammation.

Medical use

Pacibekitug is being developed to treat inflammatory conditions associated with elevated IL-6 levels, such as cardiovascular disease and CKD. It aims to reduce systemic inflammation, as measured by biomarkers like hsCRP, which is linked to adverse outcomes in these diseases. As of May 2025, Pacibekitug has not received regulatory approval and is limited to investigational use in clinical trials.

Mechanism of action

Pacibekitug is a humanized monoclonal antibody that binds to IL-6, preventing its interaction with the IL-6 receptor and subsequent activation of inflammatory pathways. By neutralizing IL-6, it reduces downstream production of acute-phase reactants like hsCRP, which are markers of systemic inflammation. This mechanism is similar to other IL-6 inhibitors but is optimized for high potency and an extended half-life.

Clinical Trials

TRANQUILITY Study

The phase 2 TRANQUILITY study evaluated Pacibekitug in patients with stage 3 or 4 CKD and hsCRP levels greater than 2 mg/L, indicating significant inflammation. The open-label, single-arm study enrolled 12 patients who received a single 960 mg subcutaneous dose of Pacibekitug. Results, announced on May 7, 2025, showed: * A median hsCRP reduction of 57% at week 12, with 80% of patients achieving hsCRP levels below 2 mg/L. * Sustained hsCRP reductions through week 24, supporting the potential for quarterly dosing. * No serious adverse events related to Pacibekitug, with a safety profile consistent with other IL-6 inhibitors. The study’s findings suggest Pacibekitug’s efficacy in reducing inflammation in CKD patients, a population at high risk for cardiovascular events.Tourmaline Bio plans to initiate a phase 2b study in 2025 to further evaluate dosing regimens and indications, including cardiovascular disease.

Safety and Side Effects

In the TRANQUILITY study, Pacibekitug was well-tolerated, with no serious adverse events reported.

References