Vamifeport, a clinical stage oral ferroportin inhibitor, alleviates murine lupus nephritis: A pilot study.

Even after immunosuppression, the rate of complete remission for proliferative lupus nephritis (LN) remains around 50%, highlighting the need for identifying novel therapeutic targets. Iron exacerbates LN, and treatment with hepcidin, the primary regulator of systemic iron metabolism, ameliorates LN. This identifies ferroportin, the only known hepcidin receptor, as a target to alleviate LN. Vamifeport is a safe oral ferroportin inhibitor with promising pharmacodynamic effect, currently in clinical development for diseases with dysregulated iron metabolism. We demonstrate that oral vamifeport administration attenuates renal pathology in MRL/lpr mice, independently of circulating autoantibodies and glomerular immune complex deposits. We identified that vamifeport reduces ferroportin expression on monocytes. LN serum-induced inflammation is attenuated only in long-term vamifeport treated monocyte-derived macrophages (MDM), but not in renal proximal tubular epithelial cells (ferroportin-expressing cells in the kidney). Collectively, our study suggests that vamifeport has a high potential to be further developed clinically as an adjunct therapeutic to treat LN.