Lonigutamab
Lonigutamab is an investigational monoclonal antibody biosimilar designed to target the insulin-like growth factor 1 receptor. It is being evaluated for its potential in treating thyroid eye disease and certain cancers, such as breast cancer, through clinical trials. Lonigutamab is expressed in Chinese hamster ovary cells and is currently limited to laboratory research applications, not approved for human therapeutic or diagnostic use.
Medical use
Lonigutamab is under investigation for its therapeutic potential in two primary areas: thyroid eye disease and breast cancer. In TED, it is being studied for its ability to mitigate symptoms such as proptosis and inflammation, while in breast cancer, it is evaluated as part of an antibody-drug conjugate to induce tumor regression in IGF-1R-overexpressing tumors.
A Phase 1/2, multicenter, multiple-dose clinical study is evaluating Lonigutamab’s efficacy and safety in subjects with TED, a condition characterized by proptosis and inflammation. The study includes patients aged 18 to 75 with a Clinical Activity Score ≥4 and proptosis ≥3 mm above normal in the most severely affected eye. Key exclusion criteria includes inflammatory bowel disease, hearing impairment, and corneal decompensation unresponsive to medical management. The primary outcome measure is the incidence and characterization of nonserious treatment-emergent adverse events from Day 1 to Day 169.
Breast cancer
Lonigutamab ugodotin, an ADC targeting IGF-1R and delivering monomethyl auristatin E as a payload, has shown promise in preclinical models of breast cancer with IGF-1R overexpression. A 2020 study demonstrated its ability to induce tumor regression without affecting normal cells. A Phase I clinical trial assessed its safety profile in advanced or metastatic tumors, including breast cancer. The study was terminated in 2024.
Mechanism of action
Lonigutamab targets IGF-1R, a receptor implicated in cell growth and survival, which is overexpressed in certain cancers and inflammatory conditions like TED. As a monoclonal antibody, it binds to IGF-1R, potentially inhibiting signaling pathways that promote tumor growth or inflammation. In its ADC form, it delivers MMAE, a cytotoxic agent, to selectively kill cancer cells.
Development and regulatory status
Lonigutamab is being developed by Acelyrin for TED applications. Its use in breast cancer is explored through collaborative research, with no regulatory approval granted as of May 2025. The drug remains a research tool, with Abbexa Ltd. explicitly stating it is not suitable for human therapeutic or diagnostic applications. Ongoing clinical trials are in early phases, and further data are needed to establish efficacy and safety.