3 Key Takeaways
Plain English Summary- 01Core Finding
Patients from the Phase 2 trial were not included in efficacy (real-world effectiveness in the trial) analyses.
- 02Study Evidence
Tested in a randomized controlled trial (174 patients) at the Phase I/II stage.
- 03Practical Meaning
Early-stage human studies — dosing, durability, and rare side effects still require Phase III confirmation.
What This Means for You
Long-term treatment with iptacopan led to sustained slowing in eGFR decline and proteinuria reduction that were also observed after switching from placebo (inactive comparison treatment). No new safety signals were observed.
The Discovery
Patients who completed APPLAUSE-IgAN or the Phase 2 iptacopan trial (NCT03373461) could enter an open-label rollover extension program (REP) (NCT04557462). Patients in this REP receive oral iptacopan 200 mg twice daily alongside supportive care. Patients from the Phase 2 trial were not included in efficacy (real-world effectiveness in the trial) analyses. Overall, 194 and 174 patients from the APPLAUSE-IgAN iptacopan and placebo (inactive comparison treatment) arms, respectively, entered the REP. In patients who received iptacopan for up to 48 months, the total annualized eGFR slope was -3.49 ml/min per 1.73 m 2 per year (95% CI -4.17, -2.80). Urine protein-to-creatinine ratio from first morning void (UPCR-FMV) reduction was sustained through 48 months with iptacopan (geometric mean ratio to baseline: 0.61 [95% CI 0.50, 0.75]). Before receiving iptacopan, the total eGFR slope over 24 months in APPLAUSE-IgAN placebo arm patients who entered the REP was -5.29 ml/min per 1.73 m 2 per year (95% CI -6.09, -4.49). After switching to iptacopan, the total eGFR slope improved to -2.11 ml/min per 1.73 m 2 per year (95% CI -3.08, -1.13) over the next 24 months. UPCR-FMV decreased after switching (geometric mean ratio to baseline at month 48: 0.74 [95% CI 0.59, 0.91]). Long-term safety up to 5 years (median treatment duration: 29.9 months) was consistent with the known profile of iptacopan.
How It Works, Simply
This nephrology research focuses on glomerular filtration & renal tubular preservation. Researchers evaluated it using a randomized controlled trial (174 patients) at the Phase I/II stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
Patients from the Phase 2 trial were not included in efficacy analyses.
- 02Study Evidence
Tested in a randomized controlled trial (174 patients) at the Phase I/II stage.
- 03Practical Meaning
Early-stage human studies — dosing, durability, and rare side effects still require Phase III confirmation.
Key Numbers
Biological Mechanism & Study Design
Study Design & Cohort
Randomized controlled trial
Randomized controlled trial (174 patients) · Phase I/II
Biological Pathway & Modality
Glomerular filtration & renal tubular preservation
Intervention: Long-term efficacy and safety for the complement factor B inhibitor
Experimental Findings & Endpoints
Patients who completed APPLAUSE-IgAN or the Phase 2 iptacopan trial (NCT03373461) could enter an open-label rollover extension program (REP) (NCT04557462).
Patients in this REP receive oral iptacopan 200 mg twice daily alongside supportive care. Patients from the Phase 2 trial were not included in efficacy analyses.
Overall, 194 and 174 patients from the APPLAUSE-IgAN iptacopan and placebo arms, respectively, entered the REP. In patients who received iptacopan for up to 48 months, the total annualized eGFR slope was -3.49 ml/min per 1.73 m 2 per year (95% CI -4.17, -2.80).
Urine protein-to-creatinine ratio from first morning void (UPCR-FMV) reduction was sustained through 48 months with iptacopan (geometric mean ratio to baseline: 0.61 [95% CI 0.50, 0.75]). Before receiving iptacopan, the total eGFR slope over 24 months in APPLAUSE-IgAN placebo arm patients who entered the REP was -5.29 ml/min per 1.73 m 2 per year (95% CI -6.09, -4.49).
After switching to iptacopan, the total eGFR slope improved to -2.11 ml/min per 1.73 m 2 per year (95% CI -3.08, -1.13) over the next 24 months. UPCR-FMV decreased after switching (geometric mean ratio to baseline at month 48: 0.74 [95% CI 0.59, 0.91]).
Long-term safety up to 5 years (median treatment duration: 29.9 months) was consistent with the known profile of iptacopan.
Clinical Translation & Practice Context
Long-term treatment with iptacopan led to sustained slowing in eGFR decline and proteinuria reduction that were also observed after switching from placebo.
No new safety signals were observed.
The Bottom Line · Clinical Pearl
“Long-term treatment with iptacopan led to sustained slowing in eGFR decline and proteinuria reduction that were also observed after switching from placebo.”
Published in Kidney International · Current Stage: Phase I/II