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Iptacopan (LNP023) is an oral, first-in-class, low molecular weight inhibitor of Factor B in clinical development for the treatment of diseases associated with activation of the alternative complement pathway. Phase 3 studies of iptacopan are ongoing in paroxysmal nocturnal hemoglobinuria, C3 glomerulonephritis, IgA nephropathy, and atypical hemolytic uremic syndrome. Previous studies indicated the liver as the primary organ of iptacopan elimination, necessitating this study.
Participants with mild (n=8; Child-Pugh [CP] score 5–6), moderate (n=8; CP score 7–9) or severe (n=6; CP score 10–15) hepatic impairment (HI) or normal liver function (n=16; control group) were enrolled. Each participant with HI was demographically matched with a control participant. All participants received a single oral dose of iptacopan 200 mg, followed by serial pharmacokinetic sampling of total and unbound iptacopan.
Treatment with iptacopan was well tolerated. The Gmean ratio (90% CI) for iptacopan Cmax and AUC are shown below for each group relative to the control group. HI had no clinically relevant effect on peak (Cmax) or total (AUC) iptacopan plasma exposure. Unbound iptacopan exposure increased by 2–4 fold in participants with severe HI.
Conclusions
The lack of effect of HI on total iptacopan exposure indicates that no dose adjustment is required. The increase in unbound iptacopan exposure with increasing severity of HI is an expected consequence of reduced hepatic protein synthesis. These results support the clinical dose of oral iptacopan 200 mg twice daily to provide durable inhibition of the alternative pathway in patients with hepatic impairment.
This abstract was also submitted for the NKF’23 congress. By submitting the abstract to WCN’24, abstract authors declare that re-submitting the abstract is permitted by the organizers of the previous meeting.