C3G/Primary IC-MPGN

Game-changing results across the trifecta of key measures

Proteinuria
Kidney function
C3 staining
Subgroup data

EMPAVELI results in proteinuria, kidney function, and C3 staining1,2

Statistically significant proteinuria reduction at Week 26, 
with reduction observed as early as Week 41,2

Primary endpoint: change in uPCR from baseline at Week 26

68%
reduction in uPCR
from baseline vs placebo1
(P<0.0001)
  • Geometric means at Week 26 vs baseline (95% CI): 0.33 (CI: 0.25, 0.43) with EMPAVELI vs 1.03 (CI: 0.91, 1.16) with placebo1

Following the 26-week randomized controlled period (RCP), a 26-week open-label period (OLP) was conducted in which all patients received EMPAVELI.

uPCR over 52 weeks2

Based on the geometric mean of uPCR compared to baseline.

These prespecified subgroup analyses were not powered to detect differences between treatment and placebo in these subgroups and results were not included in the study’s formal multiplicity-controlled testing hierarchy. Therefore, findings should be considered exploratory and interpreted descriptively. No formal statistical conclusions can be drawn.

Consider these post hoc subgroup analysis findings exploratory and interpret with caution, as these analyses were not prespecified. The study was not designed or powered to detect differences between treatment and placebo in these subgroups, and multiple comparisons increase the risk of findings due to chance. No formal conclusions can be drawn, and further prospective studies are needed to confirm these observations.

Post hoc analysis: proteinuria shifts from baseline to Week 262

Powerful kidney protection by slowing disease progression

Key secondary endpoint: a statistically significant proportion of patients met composite renal endpoint at Week 26 with EMPAVELI1

Composite renal endpoint was defined as ≥50% reduction in uPCR + stable eGFR (≤15% reduction from baseline)1

27x higher odds of achieving composite renal endpoint with EMPAVELI than placebo (P<0.0001) (95% CI: 6, 124)1

Odds ratio (EMPAVELI vs placebo)

Key secondary endpoint: change in eGFR from baseline through Week 261,2

Difference in EMPAVELI vs placebo at Week 261
+6.31 mL/min/1.73 m2
(95% CI: 0.50, 12.12)

Pharmacodynamic data: clearing of excessive C3 deposits

Reduction of C3 staining by ≥2 orders of magnitude (OOM) in evaluable patients§ taking EMPAVELI (n=35).1,2

Baseline
Week 26

74% had reduction in C3 staining by ≥2 OOM at Week 26 compared to 12% with placebo (n=34)1,2

27x higher odds of achieving ≥2 OOM reduction in C3 staining (95% Cl: 6, 116).2

Week 26
Based on an additional analysis of these pharmacodynamic data, 71.4% (n=35) saw complete clearance (0 intensity staining) vs 8.8% with placebo (n=34) at Week 26.2

1 OOM=10x; 2 OOM=100x.

Renal biopsies from a patient with post-transplant recurrent C3G. Images courtesy of Patrick D. Walker, MD, Senior Renal Pathologist at Arkana Laboratories.

§Evaluable patients included only adult patients. Renal biopsies were not performed on pediatric patients.

Results in pediatric and post-transplant C3G subgroups

These prespecified subgroup analyses were not powered to detect differences between treatment and placebo in these subgroups and results were not included in the study’s formal multiplicity-controlled testing hierarchy. Therefore, findings should be considered exploratory and interpreted descriptively. No formal statistical conclusions can be drawn.

Pediatric patients who achieved composite renal endpoint vs placebo at Week 264

Patients had a 37x higher odds of achieving composite renal endpoint with EMPAVELI than placebo4

Odds ratio (EMPAVELI vs placebo)

Change in eGFR from baseline observed at Week 26 in pediatric patients4

Difference in EMPAVELI vs placebo at Week 264

+9.7

mL/min/1.73 m2

These prespecified subgroup analyses were not powered to detect differences between treatment and placebo in these subgroups and results were not included in the study’s formal multiplicity-controlled testing hierarchy. Therefore, findings should be considered exploratory and interpreted descriptively. No formal statistical conclusions can be drawn.

Post-transplant patients with recurrent C3G who 
achieved composite renal endpoint at Week 265

60% of post-transplant recurrent C3G patients achieved composite renal endpoint at Week 265

Change in eGFR from baseline observed at Week 26 in post-transplant patients with recurrent C3G5

Difference in EMPAVELI vs placebo at Week 265
+9.3 mL/min/1.73 m2

Safety and effectiveness of EMPAVELI in patients with recurrent IC-MPGN following kidney transplant have not been established.1

These data are based on an additional analysis of pharmacodynamic data. They were not powered to detect differences between treatment and placebo in these data, and results were not included in the study’s formal multiplicity-controlled testing hierarchy. Therefore, findings should be considered exploratory and interpreted descriptively. No formal statistical conclusions can be drawn.

All post-transplant patients with recurrent C3G reduced C3 staining by ≥2 OOM at Week 26 with EMPAVELI5,||

100% of post-transplant recurrent C3G patients reduced C3 staining by ≥2 OOM at Week 26 in the treatment arm5

Results of pharmacodynamic data in patients with recurrent IC-MPGN following kidney transplant have not been established.1

|| In adults with evaluable baseline and Week 26 renal biopsies.

Discover the safety data of EMPAVELI

EMPAVELI SAFETY

FMU=first morning urine; GM=geometric mean; LS=least squares.

References: 1. EMPAVELI [prescribing information]. Waltham, MA: Apellis Pharmaceuticals, Inc.; 2025. 2. Data on file. Apellis Pharmaceuticals, Inc., Waltham, MA. 3. Nester CM, Bomback AS, Ariceta Iraola MG, et al. VALIANT: phase 3 trial of pegcetacoplan for patients with native or post-transplant recurrent C3G or primary IC-MPGN. ASN Kidney Week. 2024. 4. Vivarelli M, Ariceta G, Borovitz Y, et al. Pegcetacoplan for adolescents with C3G or IC-MPGN in phase 3 VALIANT. 3rd Annual Spring Clinical Meetings of the National Kidney Foundation. 2025. 5. Bomback AS. Pegcetacoplan for posttransplant recurrent C3 glomerulopathy or primary immune complex-mediated glomerulonephritis: the VALIANT trial. 3rd Annual Spring Clinical Meetings of the National Kidney Foundation. 2025.

IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS INFECTIONS CAUSED BY ENCAPSULATED BACTERIA

EMPAVELI, a complement inhibitor, increases the risk of serious infections, especially those caused by encapsulated bacteria, such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B. Life-threatening and fatal infections with encapsulated bacteria have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early.

  • Complete or update vaccination for encapsulated bacteria at least 2 weeks prior to the first dose of EMPAVELI, unless the risks of delaying therapy with EMPAVELI outweigh the risks of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against encapsulated bacteria in patients receiving a complement inhibitor.
  • Patients receiving EMPAVELI are at increased risk for invasive disease caused by encapsulated bacteria, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious infections and evaluate immediately if infection is suspected.

Because of the risk of serious infections caused by encapsulated bacteria, EMPAVELI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the EMPAVELI REMS.

CONTRAINDICATIONS

  • Hypersensitivity to pegcetacoplan or to any of the excipients
  • For initiation in patients with unresolved serious infection caused by encapsulated bacteria including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B

WARNINGS AND PRECAUTIONS

Serious Infections Caused by Encapsulated Bacteria

EMPAVELI, a complement inhibitor, increases a patient’s susceptibility to serious, life-threatening, or fatal infections caused by encapsulated bacteria including Streptococcus pneumoniae, Neisseria meningitidis (caused by any serogroup, including non-groupable strains), and Haemophilus influenzae type B. Life-threatening and fatal infections with encapsulated bacteria have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors. The initiation of EMPAVELI treatment is contraindicated in patients with unresolved serious infection caused by encapsulated bacteria.

Complete or update vaccination against encapsulated bacteria at least 2 weeks prior to administration of the first dose of EMPAVELI, according to the most current ACIP recommendations for patients receiving a complement inhibitor. Revaccinate patients in accordance with ACIP recommendations considering the duration of therapy with EMPAVELI. Note that ACIP recommends an administration schedule in patients receiving complement inhibitors that differs from the administration schedule in the vaccine prescribing information. If urgent EMPAVELI therapy is indicated in a patient who is not up to date with vaccines against encapsulated bacteria according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer these vaccines as soon as possible. The benefits and risks of treatment with EMPAVELI, as well as the benefits and risks of antibacterial drug prophylaxis in unvaccinated or vaccinated patients, must be considered against the known risks for serious infections caused by encapsulated bacteria.

Vaccination does not eliminate the risk of serious encapsulated bacterial infections, despite development of antibodies following vaccination. Closely monitor patients for early signs and symptoms of serious infection and evaluate patients immediately if an infection is suspected. Inform patients of these signs and symptoms and instruct patients to seek immediate medical care if these signs and symptoms occur. Promptly treat known infections. Serious infection may become rapidly life-threatening or fatal if not recognized and treated early. Consider interruption of EMPAVELI in patients who are undergoing treatment for serious infections.

EMPAVELI is available only through a restricted program under a REMS.

EMPAVELI REMS

EMPAVELI is available only through a restricted program under a REMS called EMPAVELI REMS, because of the risk of serious infections caused by encapsulated bacteria. Notable requirements of the EMPAVELI REMS include the following:

Under the EMPAVELI REMS, prescribers must enroll in the program. Prescribers must counsel patients about the risks, signs, and symptoms of serious infections caused by encapsulated bacteria, provide patients with the REMS educational materials, ensure patients are vaccinated against encapsulated bacteria at least 2 weeks prior to the first dose of EMPAVELI, prescribe antibacterial drug prophylaxis if patients’ vaccine status is not up to date and treatment must be started urgently, and provide instructions to always carry the Patient Safety Card both during treatment, as well as for 2 months following last dose of EMPAVELI. Pharmacies that dispense EMPAVELI must be certified in the EMPAVELI REMS and must verify prescribers are certified.

Further information is available at www.empavelirems.com or 1-888-343-7073.

Infusion-Related Reactions

Systemic hypersensitivity reactions (eg, facial swelling, rash, urticaria, pyrexia) have occurred in patients treated with EMPAVELI, which may resolve after treatment with antihistamines. Cases of anaphylaxis leading to treatment discontinuation have been reported. If a severe hypersensitivity reaction (including anaphylaxis) occurs, discontinue EMPAVELI infusion immediately, institute appropriate treatment, per standard of care, and monitor until signs and symptoms are resolved.

Interference with Laboratory Tests

There may be interference between silica reagents in coagulation panels and EMPAVELI that results in artificially prolonged activated partial thromboplastin time (aPTT); therefore, avoid the use of silica reagents in coagulation panels.

ADVERSE REACTIONS

Most common adverse reactions in adult and pediatric patients 12 years of age and older with C3G or primary IC-MPGN (incidence ≥10%) were infusion-site reactions, pyrexia, nasopharyngitis, influenza, cough, and nausea.

USE IN SPECIFIC POPULATIONS

Females of Reproductive Potential

EMPAVELI may cause embryo-fetal harm when administered to pregnant women. Pregnancy testing is recommended for females of reproductive potential prior to treatment with EMPAVELI. Advise female patients of reproductive potential to use effective contraception during treatment with EMPAVELI and for 40 days after the last dose.

INDICATION

EMPAVELI® (pegcetacoplan) is indicated for the treatment of adult and pediatric patients aged 12 years and older with C3 glomerulopathy (C3G) or primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN), to reduce proteinuria.

Please see full Prescribing Information, including Boxed WARNING regarding serious infections caused by encapsulated bacteria, and Medication Guide.

C3G/Primary IC-MPGN
  • EXPAND
  • COLLAPSE

IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS INFECTIONS CAUSED BY ENCAPSULATED BACTERIA

EMPAVELI, a complement inhibitor, increases the risk of serious infections, especially those caused by encapsulated bacteria, such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B. Life-threatening and fatal infections with encapsulated bacteria have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early.

  • Complete or update vaccination for encapsulated bacteria at least 2 weeks prior to the first dose of EMPAVELI, unless the risks of delaying therapy with EMPAVELI outweigh the risks of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against encapsulated bacteria in patients receiving a complement inhibitor.
  • Patients receiving EMPAVELI are at increased risk for invasive disease caused by encapsulated bacteria, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious infections and evaluate immediately if infection is suspected.

Because of the risk of serious infections caused by encapsulated bacteria, EMPAVELI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the EMPAVELI REMS.

CONTRAINDICATIONS

  • Hypersensitivity to pegcetacoplan or to any of the excipients
  • For initiation in patients with unresolved serious infection caused by encapsulated bacteria including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B

WARNINGS AND PRECAUTIONS

Serious Infections Caused by Encapsulated Bacteria

EMPAVELI, a complement inhibitor, increases a patient’s susceptibility to serious, life-threatening, or fatal infections caused by encapsulated bacteria including Streptococcus pneumoniae, Neisseria meningitidis (caused by any serogroup, including non-groupable strains), and Haemophilus influenzae type B. Life-threatening and fatal infections with encapsulated bacteria have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors. The initiation of EMPAVELI treatment is contraindicated in patients with unresolved serious infection caused by encapsulated bacteria.

Complete or update vaccination against encapsulated bacteria at least 2 weeks prior to administration of the first dose of EMPAVELI, according to the most current ACIP recommendations for patients receiving a complement inhibitor. Revaccinate patients in accordance with ACIP recommendations considering the duration of therapy with EMPAVELI. Note that ACIP recommends an administration schedule in patients receiving complement inhibitors that differs from the administration schedule in the vaccine prescribing information. If urgent EMPAVELI therapy is indicated in a patient who is not up to date with vaccines against encapsulated bacteria according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer these vaccines as soon as possible. The benefits and risks of treatment with EMPAVELI, as well as the benefits and risks of antibacterial drug prophylaxis in unvaccinated or vaccinated patients, must be considered against the known risks for serious infections caused by encapsulated bacteria.

Vaccination does not eliminate the risk of serious encapsulated bacterial infections, despite development of antibodies following vaccination. Closely monitor patients for early signs and symptoms of serious infection and evaluate patients immediately if an infection is suspected. Inform patients of these signs and symptoms and instruct patients to seek immediate medical care if these signs and symptoms occur. Promptly treat known infections. Serious infection may become rapidly life-threatening or fatal if not recognized and treated early. Consider interruption of EMPAVELI in patients who are undergoing treatment for serious infections.

EMPAVELI is available only through a restricted program under a REMS.

EMPAVELI REMS

EMPAVELI is available only through a restricted program under a REMS called EMPAVELI REMS, because of the risk of serious infections caused by encapsulated bacteria. Notable requirements of the EMPAVELI REMS include the following:

Under the EMPAVELI REMS, prescribers must enroll in the program. Prescribers must counsel patients about the risks, signs, and symptoms of serious infections caused by encapsulated bacteria, provide patients with the REMS educational materials, ensure patients are vaccinated against encapsulated bacteria at least 2 weeks prior to the first dose of EMPAVELI, prescribe antibacterial drug prophylaxis if patients’ vaccine status is not up to date and treatment must be started urgently, and provide instructions to always carry the Patient Safety Card both during treatment, as well as for 2 months following last dose of EMPAVELI. Pharmacies that dispense EMPAVELI must be certified in the EMPAVELI REMS and must verify prescribers are certified.

Further information is available at www.empavelirems.com or 1-888-343-7073.

Infusion-Related Reactions

Systemic hypersensitivity reactions (eg, facial swelling, rash, urticaria, pyrexia) have occurred in patients treated with EMPAVELI, which may resolve after treatment with antihistamines. Cases of anaphylaxis leading to treatment discontinuation have been reported. If a severe hypersensitivity reaction (including anaphylaxis) occurs, discontinue EMPAVELI infusion immediately, institute appropriate treatment, per standard of care, and monitor until signs and symptoms are resolved.

Interference with Laboratory Tests

There may be interference between silica reagents in coagulation panels and EMPAVELI that results in artificially prolonged activated partial thromboplastin time (aPTT); therefore, avoid the use of silica reagents in coagulation panels.

ADVERSE REACTIONS

Most common adverse reactions in adult and pediatric patients 12 years of age and older with C3G or primary IC-MPGN (incidence ≥10%) were infusion-site reactions, pyrexia, nasopharyngitis, influenza, cough, and nausea.

USE IN SPECIFIC POPULATIONS

Females of Reproductive Potential

EMPAVELI may cause embryo-fetal harm when administered to pregnant women. Pregnancy testing is recommended for females of reproductive potential prior to treatment with EMPAVELI. Advise female patients of reproductive potential to use effective contraception during treatment with EMPAVELI and for 40 days after the last dose.

INDICATION

EMPAVELI® (pegcetacoplan) is indicated for the treatment of adult and pediatric patients aged 12 years and older with C3 glomerulopathy (C3G) or primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN), to reduce proteinuria.

Please see full Prescribing Information, including Boxed WARNING regarding serious infections caused by encapsulated bacteria, and Medication Guide.