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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. Preclinical studies identified CYP2C8, OATP and P-gp as potential sources of drug–drug interactions with iptacopan that warranted clinical investigation.
In total, 56 healthy participants were enrolled into three separate cohorts (17–21 participants per cohort) to study the following interactions: iptacopan as a victim of CYP2C8 or OATP inhibition, and iptacopan as a perpetrator of P-gp or OATP inhibition. Test compounds used are shown (Table). All perpetrator drugs, including iptacopan 200 mg twice daily, were dosed to steady state. A single dose of iptacopan 100 mg was used as a victim drug.
Treatment with iptacopan treatment was well tolerated. Mean (standard deviation [SD]) oral drug clearance (CL/F) and volume of distribution (Vz/F) are shown for the four different drug–drug interactions (Table). In all cases, there was no significant change in how the drug was cleared from the body (CL/F) or distributed (Vz/F).
These data show that iptacopan has no relevant effect on the systemic exposure of P-gp or OATP transported drugs, and CYP2C8 or OATP inhibition have a ≤50% effect on systemic exposure of iptacopan. This finding provides reassurance that iptacopan can be used in patients on complex drug regimens without clinically relevant, iptacopan-related drug–drug interactions.
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.