Hepcidin monoclonal antibody LY2787106 a promising new agent for cancer patients with anaemia
LY2787106, a novel fully humanized monoclonal antibody (mAb) with high affinity for hepcidin, is a well tolerated and effective therapy for regulating iron levels in cancer patients with anaemia, say US-based researchers.
They evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of LY2787106 in a first-in-human phase 1, multicentre trial. Thirty-three cancer patients with anaemia and hepcidin levels ≥5 ng/mL received intravenous LY2787106 (0.30–10.0 mg/kg once every 3 weeks) as part of a dose escalation study to evaluate safety (n=19) or eight weekly doses of LY2787106 (10 mg/kg) with or without iron supplementation in order to elucidate the effect of LY2787106 on haemoglobin levels (n=14). [J Hematol Oncol 2017;10:73]
LY2787106 was well tolerated with no dose-limiting toxicities noted during the dose escalation part of the trial. It was also effective – the mean change in haemoglobin level was -0.2 g/dL and -0.5 g/dL from baseline among patients who did and did not receive oral iron supplementation during the second part of the trial. However, effects on iron mobilization and reticulocyte count were transient. Increases in serum iron and transferrin saturation typically peaked within 24 hours and returned to baseline by day 8.
The researchers concluded that their findings support the key role played by hepcidin in iron regulation and suggest that targeting the hepcidin-ferroportin pathway with a mAb is a promising strategy. They are currently evaluating the safety and efficacy of agents that affect other key components of the pathway, including ferroportin.