Efficacy data for FABHALTA^® (iptacopan)

IN ADULTS WITH PRIMARY IgAN TAKING MAXIMALLY TOLERATED RASi ± SGLT2i TREATMENT

FABHALTA helped preserve kidney function better than placebo¹

FABHALTA significantly slowed eGFR decline over 24 months vs placebo¹

ANNUALIZED MEAN CHANGE FROM BASELINE IN eGFR (mL/min/1.73 m²) ESTIMATED OVER A 24-MONTH PERIOD

Mean change from baseline in eGFR (mL/min/1.73 m²) by visit¹

The mean change from baseline in eGFR was estimated from an MMRM with stratification factors: geographic region, baseline eGFR, and baseline UPCR. MMRM analysis included all eGFR data during the double-blind period up to Month 24 regardless of treatment discontinuation for any reason, with the exception of the initiation of kidney replacement therapy, which was handled by a worst-case imputation method.

*Represents the number of patients with values nonmissing and not imputed as per the intercurrent event handling strategy by visit and treatment group.

PRESPECIFIED EXPLORATORY SUBGROUP ANALYSIS

​Prespecified exploratory subgroup analyses: annualized total eGFR slope estimated over 24 months²

The subgroup analyses of the primary end point are exploratory and are neither adjusted for multiplicity nor powered to establish superiority of FABHALTA over placebo. These data are descriptive in nature, presented for observation only, and should be interpreted with caution. No formal conclusions or comparisons between the 2 treatment arms can be made.

ANNUALIZED TOTAL eGFR SLOPE ESTIMATED OVER 24 MONTHS ACROSS PRESPECIFIED SUBGROUPS DEFINED BY BASELINE DEMOGRAPHICS AND CLINICAL CHARACTERISTICS

Intercurrent events handled with hypothetical strategy: values after the intake of corticosteroid therapy/immunosuppressant therapy, other newly approved drugs for IgAN, and kidney replacement therapy initiation were imputed under jump to reference and missing at random for the LNP023 and placebo groups, respectively; values after initiation of new background therapy for IgAN were imputed under missing at random. 
Treatment discontinuation was handled with a treatment policy strategy. 
The same model as for the analysis of the primary estimand for eGFR slope was used; for subgroups that are also stratification factors, the corresponding stratification factor term was removed from the model. 
In cases where model convergence was not achieved due to small subgroup size, results are not displayed in the forest plot.

EXPLORATORY END POINT

Substantial reduction in proteinuria observed with FABHALTA at Month 9 and at Month 24^1,2

Final analysis exploratory end point

PERCENT REDUCTION IN UPCR (g/g) (FROM 24-HOUR URINE COLLECTION) FROM BASELINE*

Intercurrent events handled with hypothetical strategy: values after the intake of corticosteroid therapy/immunosuppressant therapy, other newly approved drugs for IgAN, and kidney replacement therapy initiation were imputed under jump to reference and missing at random for LNP023 and placebo, respectively; values after initiation of new background therapy for IgAN were imputed under missing at random.

Treatment discontinuation for any reason was handled by the treatment policy strategy. Log transformed ratio to baseline was analyzed using an MMRM including treatment, timepoint (as categorical variable), randomization strata as fixed effects, treatment*timepoint and treatment*log (baseline UPCR 24-hour) as interaction terms and baseline log (UPCR 24-hour) as a fixed covariate.

Results were back-transformed and expressed as geometric means.

EXPLORATORY END POINT

Rapid reduction in UPCR first morning void (FMV) observed with FABHALTA at Week 2 and sustained through Month 24¹

GM PERCENT CHANGE FROM BASELINE IN UPCR FMV AND 24-HOUR UPCR BY VISIT¹

Log transformed ratio to baseline in UPCR was analyzed using an MMRM with stratification factors: geographic region, baseline eGFR, and baseline UPCR. MMRM analysis included UPCR data during the double-blind period up to Month 24 based on all patients. UPCR data after the intercurrent events and missing data were handled by the predefined strategies and imputation approaches. 24-hour UPCR and UPCR FMV were analyzed separately using the same analysis method.

*Represents the number of patients with values nonmissing and not imputed as per the intercurrent event handling strategy by visit and treatment group.

KEY SECONDARY END POINT

FABHALTA significantly delayed time to first occurrence of a kidney composite event over 24 months vs placebo¹

Time to first occurrence of a kidney composite event was defined as reaching either:

• Sustained ≥30% decline in eGFR from baseline over ≥4 weeks,

• Sustained eGFR <15 mL/min/1.73 m² over ≥4 weeks,

• Maintenance dialysis over ≥4 weeks,

• Receipt of kidney transplant, or

• Death from kidney failure

The treatment effect was driven by an effect on a sustained decline in eGFR ≥30% from baseline.

TIME TO FIRST OCCURRENCE OF A KIDNEY COMPOSITE END POINT*

In total, 4 patients in the FABHALTA arm and 6 in the placebo arm had sustained eGFR <15 mL/min/1.73 m2; 6 patients in the FABHALTA arm and 4 in the placebo arm required maintenance dialysis; 2 patients in the placebo arm had receipt of kidney transplant; and no patients died during the study.

*For patients with multiple events, only the first event contributing to the composite end point is counted in the table.

^†Hazard ratio <1 in favor of FABHALTA. Analyzed using Cox proportional hazards model.

^‡Adjusted P value. 

^§Over at least 4 weeks.