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During the congress, E-Posters will be accessible to all participants on the congress website 24/7, as well as in the E-poster stations in the congress center.
Preparing your E-Poster
Please review the E-Poster format requirements carefully when preparing your E-Poster. Should your E-Poster not meet the mentioned requirements, it may not be displayed as described above.
E-Poster Submission Deadline
Please prepare and upload your E-Poster no later than March 14, 2026 11.59PM CET. After this date, you will no longer be able to prepare and upload your E-poster and it will not be displayed and accessible on the congress website.
Please follow the instructions below to input your abstract title.
Abstract titles should be brief and reflect the content of the abstract.
Dysregulation of the complement alternative pathway (AP) contributes to progression of IgA nephropathy (IgAN). Elevated Factor B (FB), a key AP protein, is linked to proteinuria and kidney function decline. Sefaxersen is a GalNAc-conjugated antisense oligonucleotide (ASO) designed for targeted hepatic delivery to suppress FB production. It is the first AP mRNA-targeting therapy in late-stage development for IgAN. In Phase 1 and 2 studies, sefaxersen was well tolerated and markedly reduced systemic FB and AH50, a measure of alternative complement pathway activity. Ethnic sensitivity assessments are critical in global drug development to ensure safe and effective use across populations. For ASOs, limited clinical experience exists regarding potential ethnic differences in pharmacokinetics (PK) and pharmacodynamics (PD). A population PK and PK/PD analysis was conducted to assess ethnic effects (Asian vs. non-Asian) on the PK of sefaxersen and on the plasma FB profiles as the PD effect.
Plasma PK and PD data from Phase 1 single-ascending dose (696844-CS1) and multiple-ascending dose studies (696844-CS2) in healthy volunteers, including Phase 1 single-dose studies in China (YA45226) and Japan (JH44879), were pooled with data from two Phase 2 studies in patients with IgAN (696844-CS4) and Geographic Atrophy (696844-CS5). Sefaxersen was administered subcutaneously across a dose range of 10 to 100 mg. The pooled dataset included 45 Asian and 274 non-Asian participants. Concentration–time profiles and exposure–response relationships were analyzed using nonlinear mixed-effects modeling. Baseline covariates tested in the population PK and PK/PD models included ethnicity (Asian vs. non-Asian) and body weight. PD effects, measured as the time course of plasma FB, were characterized using an indirect-response model. Simulations of PK and PD profiles at steady state were performed to compare Asian and non-Asian participants under the proposed clinical dosing regimen.
The PK of sefaxersen was best described by a two-compartment model with first-order absorption and linear elimination. Its pharmacological effect on FB production was characterized by an indirect-response model with an inhibitory drug effect.
The distribution of individual random effects (ETAs) for key PK parameters (KA, CL/F, Vc/F, Q/F, Vp/F, and F1) was similar between Asian and non-Asian participants. Median values and variability overlapped across groups, and no systematic ethnic trends were observed. Similarly, for the PD (plasma FB) model, the distributions of ETAs for baseline (E₀), turnover rate constant (Kout), and potency (IC₅₀) were likewise comparable between Asian and non-Asian participants. These findings indicate that ethnicity had no clinically meaningful impact on the PK or PD of sefaxersen, supporting consistent exposure–response relationships across populations.
Sefaxersen had comparable PK and PD profiles in Asian and non-Asian participants. These results confirm the global applicability of the 70 mg regimen (Days 1, 15, and 29, then every 4 weeks) currently being evaluated in the Phase 3 ‘IMAgINATION’ study in IgAN (NCT05797610).
