Human GM-CSF-R Antibody - Mavrilimumab Biosimilar

Mavrilimumab and GM-CSF background

Mavrilimumab is a fully human IgG4 monoclonal antibody that targets the alpha subunit of the granulocyte–macrophage colony-stimulating factor receptor (GM-CSFR), effectively blocking GM-CSF signaling [1].

GM-CSF, also known as CSF2, belongs to the β-common chain cytokine family [2]. It promotes the differentiation, activation, and survival of cells from the myeloid compartment, notably macrophages, dendritic cells, and neutrophils [1, 3]. Although originally identified as a hematopoietic growth factor, this cytokine is now regarded as a pleiotropic regulator of inflammation in response to pathogens, autoimmune diseases, and cancer [2,4]. 

GM-CSF signalization requires a multimeric structure comprising four α chains (GMRα, aka CD116), four β chains (GMRβ, CD131), and four cytokines. This 12-protein complex allows the juxtaposition of the intracellular Janus kinase 2 (JAK2) and activation of the signal transducer and activator of transcription 5 (STAT5) [2]. Other signaling pathways include ERK, NF-κB, and AKT pathways [2, 5]. The understanding of cellular and molecular mechanisms whereby GM-CSF exerts its varied functions is key for the development of therapeutic strategies (e.g. cancer vaccines, blocking antibodies) [2]. 

As of June 2025,  Mavrilimumab (CAM-3001) is not yet FDA-approved. It is still under clinical investigation for the treatment of various autoimmune diseases, including rheumatoid arthritis (RA) and giant cell arteritis (GCA) [3,6]. 

Mavrilimumab has demonstrated efficacy in clinical trials for RA, showing significant reductions in disease activity scores and improvements in patient outcomes [3]. Moreover, in GCA, a phase II randomized, double-blind, placebo-controlled trial showed that mavrilimumab significantly reduced the risk of disease flare and increased sustained remission rates compared to placebo [6]. Mavrilimumab has also been investigated for the treatment of severe COVID-19 pneumonia with systemic hyperinflammation [7].

References:

1. Burmester GR, et al., 2011. Mavrilimumab, a human monoclonal antibody targeting GM-CSF receptor-α, in subjects with rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase I, first-in-human study. Ann Rheum Dis. ;70(9):1542-9.
2. Dougan M. et al., 2019. GM-CSF, IL-3, and IL-5 family of cytokines: regulators of inflammation. Immunity. 50(4):796-811.
3. Burmester GR, et al. 2017. A randomised phase IIb study of mavrilimumab, a novel GM-CSF receptor alpha monoclonal antibody, in the treatment of rheumatoid arthritis. Ann Rheum Dis. 76(6):1020-1030.
4. Zhan Y. et al., 2019. The Pleiotropic Effects of the GM-CSF Rheostat on Myeloid Cell Differentiation and Function: More Than a Numbers Game. Front Immunol. 102679.
5. Hamilton J.A., 2020. GM-CSF in inflammation. J. Exp . Med. 217(1):e20190945.
6. Cid MC, et al., 2022. Efficacy and safety of mavrilimumab in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2022 May;81(5):653-661.
7. Cremer PC, et al., 2021. Mavrilimumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation (MASH-COVID): an investigator-initiated, multicentre, double-blind, randomised, placebo-controlled trial. Lancet Rheumatol. 2021 Jun;3(6):e410-e418.