FDA Approves Apellis' EMPAVELI® (pegcetacoplan) as the First C3G and Primary IC-MPGN Treatment for Patients 12 and Older

• Proven efficacy across all three key markers of disease—68% reduction in proteinuria, stabilization of kidney function, and substantial clearance of C3 deposits

• Broad label includes adults and adolescents with C3G or primary IC-MPGN, and post-transplant C3G disease recurrence

• Well-established safety profile, consistent across >2,200 patient years in approved indications

• C3G and primary IC-MPGN are rare kidney diseases with high risk of kidney failure

• Conference call tomorrow at 8:00 a.m. ET
  
  

WALTHAM, Mass., July 28, 2025 (GLOBE NEWSWIRE) -- Apellis Pharmaceuticals, Inc. (NASDAQ:APLS) today announced that the U.S. Food and Drug Administration (FDA) has approved EMPAVELI^® (pegcetacoplan) as the first treatment for C3 glomerulopathy (C3G) or primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) in patients 12 years of age and older, to reduce proteinuria. C3G and primary IC-MPGN are rare kidney diseases, affecting 5,000 people in the United States.¹

"I'm excited to now have a highly effective therapy for a broad range of patients living with C3G and primary IC-MPGN," said Carla Nester, M.D., MSA, FASN, lead principal investigator for the VALIANT study, professor of internal medicine and pediatrics and director of pediatric nephrology, University of Iowa Stead Family Children's Hospital. "With standard of care, patients living with these rare and severe diseases frequently progress to kidney failure, necessitating lifelong dialysis and/or a kidney transplant. Given the urgent need, particularly in children, the approval of EMPAVELI marks a pivotal moment in the treatment of rare kidney diseases."

In the Phase 3 VALIANT study, EMPAVELI demonstrated an unprecedented 68% reduction in proteinuria, stabilization of kidney function, and substantial clearance of C3 deposits as measured by C3 staining, compared to placebo. The positive results were consistent across adolescent and adult patients with C3G and primary IC-MPGN, and in C3G patients with post-transplant disease recurrence.

"EMPAVELI has the potential to be truly transformational for patients with C3G and primary IC-MPGN, who until now have had very few treatment options. In the largest pivotal study of these diseases, EMPAVELI demonstrated its potential to preserve kidney function by controlling all three key markers of disease," said Cedric Francois, M.D., Ph.D., co-founder and chief executive officer, Apellis. "As Apellis' third approval in four years, this milestone underscores the unique ability of targeting C3 to improve patients' lives. We are deeply grateful to everyone who made this approval possible and look forward to building on this momentum as we advance pivotal studies of EMPAVELI in other rare kidney diseases."

"The approval of EMPAVELI is a historic milestone for people living with C3G and primary IC-MPGN, many of whom are adolescents or young adults," said Josh Tarnoff, chief executive officer, NephCure. "We recognize Apellis' commitment to these patients and their families, and to the research and innovation that will bring this life-changing treatment into the hands of patients that need it most."

The approval of EMPAVELI is based on positive six-month results from the VALIANT study, demonstrating benefits across all three key markers of disease:

• Proteinuria reduction: The study met its primary endpoint, demonstrating a statistically significant 68% (p<0.0001) proteinuria reduction in EMPAVELI-treated patients compared to placebo.
• Stabilization of kidney function: EMPAVELI-treated patients achieved stabilization of kidney function compared to placebo (nominal p=0.03) as measured by estimated glomerular filtration rate (eGFR).
• Reduction of C3 staining: A majority of EMPAVELI-treated patients achieved a reduction in C3 staining intensity (nominal p<0.0001) compared to placebo. 71% of EMPAVELI-treated patients achieved zero C3 staining intensity, demonstrating complete clearance of C3 deposits. 
  
  

The safety profile of EMPAVELI is well-established, with >2,200 patient years across all approved indications. The most common adverse reactions in the VALIANT study (≥10%) were infusion site reactions, pyrexia, nasopharyngitis, influenza, cough, and nausea. 

Apellis is committed to helping patients with treatment access and support. ApellisAssist^® is a program designed to help EMPAVELI patients along their treatment journey by providing a comprehensive system of support including help navigating insurance coverage, financial assistance for eligible patients, disease education, and ongoing product support. Patients and healthcare providers can call 1-888-273-5547 for more information.

Conference Call and Webcast

Apellis will host a conference call and webcast to discuss the FDA's approval of EMPAVELI tomorrow, July 29, 2025 at 8:00 a.m. ET. To access the live call by phone, please pre-register for the call here. A live audio webcast of the event and accompanying slides may also be accessed through the "Events and Presentations" page of the "Investors and Media" section of the company's website. A replay of the webcast will be available for 30 days following the event.

About C3 Glomerulopathy (C3G) and Primary Immune-Complex Membranoproliferative Glomerulonephritis (IC-MPGN)

C3G and primary IC-MPGN are rare and debilitating kidney diseases that can lead to kidney failure. Excessive C3 deposits are a key marker of disease activity, which can lead to kidney inflammation, damage, and failure. Approximately 50% of people living with C3G and primary IC-MPGN suffer from kidney failure within five to 10 years of diagnosis, requiring a burdensome kidney transplant or lifelong dialysis therapy.^2-4 Additionally, approximately 90% of patients who previously received a kidney transplant will experience disease recurrence.⁵ The diseases are estimated to affect 5,000 people in the United States and up to 8,000 in Europe.¹ 

About the VALIANT Study

The VALIANT Phase 3 study (NCT05067127) was a randomized, placebo-controlled, double-blinded, multi-center study that evaluated EMPAVELI® (pegcetacoplan) efficacy and safety in 124 patients who were 12 years of age and older with C3G or primary IC-MPGN. It is the largest single trial conducted in these populations and the only study to include pediatric and adult patients, with native and post-transplant kidneys. Study participants were randomized to receive EMPAVELI or placebo twice weekly for 26 weeks. Following this 26-week randomized controlled period, patients were able to proceed to a 26-week open-label phase in which all patients received EMPAVELI. The primary endpoint of the study was the log transformed ratio of urine protein-to-creatinine ratio (UPCR) at Week 26 compared to baseline.

About EMPAVELI^®/Aspaveli^® (pegcetacoplan)

EMPAVELI^®/Aspaveli^® (pegcetacoplan) is a targeted C3 therapy designed to regulate excessive activation of the complement cascade, part of the body's immune system, which can lead to the onset and progression of many serious diseases. It is approved for the treatment of C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) in the United States and paroxysmal nocturnal hemoglobinuria (PNH) in the United States, European Union, and other countries globally. The therapy is also under investigation for other rare diseases.

U.S. Important Safety Information for EMPAVELI

BOXED 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.

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

About Apellis

Apellis Pharmaceuticals, Inc. is a global biopharmaceutical company leading the way in complement science to develop life-changing therapies for some of the most challenging diseases patients face. We ushered in the first new class of complement medicine in 15 years and now have two C3-targeting medicines approved to treat four serious diseases. Breakthroughs for patients include the first-ever therapy for geographic atrophy, a leading cause of blindness, and the first treatment for patients 12 and older with C3G or primary IC-MPGN, two severe, rare kidney diseases. We believe we have only begun to unlock the potential of targeting C3 across many serious diseases. For more information, please visit http://apellis.com or follow us on LinkedIn and X.

Apellis Forward-Looking Statement 

Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute "forward-looking statements" within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements regarding the potential market opportunity of EMPAVELI for C3G and IC-MPGN. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including whether the clinical trial results of EMPAVELI for C3G and IC-MPGN indicate an effect that is greater than the actual positive effect; and any other factors discussed in the "Risk Factors" section of Apellis' Annual Report on Form 10-K with the Securities and Exchange Commission on February 28, 2025 and the risks described in other filings that Apellis may make with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Apellis specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.

Media:

Tracy Vineis

[email protected]

617.420.4839

Investors: 

Neil Carnahan, CFA

[email protected]

617.977.5703

References

1. Data on file using literature consensus. 

2. Smith RJH, et al. Nat Rev Nephrol. 2019;15(3):129-143.

3. Servais A, et al. Kidney Int. 2012;82(4):454-464.

4. Zand L, et al. J Am Soc Nephrol. 2014;25(5):1110-1117.

5. Tarragón, B, et al. C3 Glomerulopathy Recurs Early after Kidney Transplantation in Serial Biopsies Performed within the First 2 Years after Transplantation. Clinical Journal of the American Society of Nephrology. August 2024; 19(8)1005-1015. doi: 10.2215/CJN.0000000000000474.

A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/4fa47f8b-688f-4233-a671-6fe022cb99b7