Apellis Highlights New Phase 3 Data Showing EMPAVELI Sustains Kidney Function And Proteinuria Reduction In Rare Kidney Diseases

Author: Benzinga Newsdesk | October 20, 2025 06:13am

Apellis Pharmaceuticals, Inc. (NASDAQ:APLS) today announced new data from the open-label period of the Phase 3 VALIANT study that reinforce the robust and sustained efficacy of EMPAVELI® (pegcetacoplan), a C3 inhibitor, in patients with C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN), rare and debilitating kidney diseases.

Among seven EMPAVELI presentations at the upcoming American Society of Nephrology (ASN) Kidney Week, the new results build on previous data showing durable reductions in proteinuria and stable kidney function over one year with EMPAVELI.

"These results further reinforce EMPAVELI's ability to deliver meaningful, lasting benefits for patients with C3G and primary IC-MPGN, with consistent efficacy across patient groups," said Peter Hillmen, M.B. Ch.B., Ph.D., chief medical advisor, rare disease, Apellis. "As the only approved treatment for C3G and primary IC-MPGN in patients 12 years and older, EMPAVELI has the potential to transform care for people living with these rare diseases, who have a high risk of kidney failure."

New One-Year Phase 3 VALIANT Data Reinforce EMPAVELI's Robust and Sustained Treatment Effect

• Maintained proteinuria reduction regardless of immunosuppressant use or baseline proteinuria levels: Through one year, EMPAVELI sustained the significant 68% proteinuria reduction versus placebo (p<0.0001) achieved at Week 26, with consistent efficacy in patients who were or were not taking immunosuppressants and independent of baseline proteinuria levels.
  
   
• Complete proteinuria remission achieved in one-third of patients and sustained through one year: One-third of EMPAVELI-treated patients achieved complete proteinuria remission (urine protein-to-creatinine ratio [UPCR] ≤0.5 g/g) compared to 3% for placebo at week 26. These benefits were maintained through one year, and patients who switched from placebo experienced similar improvements.

Additionally, EMPAVELI continued to stabilize kidney function as measured by estimated glomerular filtration rate (eGFR), a key measure of kidney function. EMPAVELI showed favorable safety and tolerability, consistent with its established profile. There were no new safety signals.

EMPAVELI Was Superior to Iptacopan in Reducing Proteinuria Levels and Achieving the Composite Renal Endpoint in C3G Patients 

Two anchored indirect treatment comparisons (ITCs) were conducted using individual data from patients with C3G from the Phase 3 VALIANT study of EMPAVELI and published data from the Phase 3 APPEAR-C3G trial of iptacopan. The Bucher method, which preserves randomization, was used as the primary analysis with a matching-adjusted indirect comparison (MAIC), which adjusts for trial differences, as a supportive analysis.

These analyses indicate that EMPAVELI was superior to iptacopan in lowering proteinuria levels and achieving the composite renal endpoint, which combines proteinuria reduction and stabilization of eGFR. A significantly greater proportion of EMPAVELI-treated patients achieved a UPCR reduction to less than 1 g/g, at least a 50% reduction in UPCR, and the composite renal endpoint. EMPAVELI was also numerically favored over iptacopan on improvement in eGFR.

In the absence of a head-to-head study, anchored ITCs are valid and accepted methods for comparative effectiveness research used by health technology assessment bodies around the world.1,2 As with other indirect treatment comparisons, these studies may not adjust for all confounding factors due to differences inherent in study design and entry criteria. Key limitations include differences in the route of administration, treatment administration schedule, and dosing regimen.



Presentation Details:

Oral Presentation

• Pegcetacoplan for 52 weeks results in sustained proteinuria reduction to remission (≤0.5 g/g) and normalization (≤0.2 g/g): Phase 3 VALIANT trial - Carla M. Nester, MD, MSA, FASN - Glomerular Targeted Therapies: The New Era - Saturday, November 8 - 4:50-5:00 p.m. CT
  
   

Poster Presentations

• Pegcetacoplan for 52 weeks maintains proteinuria reduction regardless of immunosuppressant use or nephrotic-range proteinuria at baseline: VALIANT subgroup analysis - Carla M. Nester, MD, MSA, FASN - Friday, November 7 - 10:00 am. - 12:00 p.m. CT - Poster FR-PO0836
• Pegcetacoplan for 52 weeks maintains proteinuria reduction and eGFR stabilization in pediatric patients: Phase 3 VALIANT subgroup analysis - Larry A. Greenbaum, MD - Friday, November 7 - 10:00 a.m. - 12:00 p.m. CT - Poster FR-PO0693
• Clinical efficacy of pegcetacoplan versus iptacopan in patients with C3 glomerulopathy: Indirect treatment comparisons - Bradley P Dixon, MD - Saturday, November 8 - 10:00 a.m. - 12:00 p.m. CT - Poster SA-PO0826​
• Human factors validation of a pegcetacoplan on-body injector demonstrates ease of use by adolescents with C3 glomerulopathy / primary immune-complex membranoproliferative glomerulonephritis - Eliyahu Khankin, MD - Friday, November 7 - 10:00 a.m. - 12:00 p.m. CT - Poster FR-PO0890
• Pegcetacoplan for adolescents and adults with C3 glomerulopathy or primary immune-complex membranoproliferative glomerulonephritis: Enrollment status of the VALE extension - Eliyahu Khankin, MD - Thursday, November 6, 2025 - 10:00 a.m. to 12:00 p.m. CT - Poster INFO15-TH
• Pegcetacoplan for adults with high risk of delayed graft function: A phase 3, randomized, placebo-controlled trial - Eliyahu Khankin, MD - Thursday, November 6 - 10:00 a.m. to 12:00 p.m. CT - Poster INFO16-TH

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