The New England Journal of Medicine Publishes Positive Phase 3 VALIANT Results of EMPAVELI® (pegcetacoplan) for C3G and Primary IC-MPGN

Rhea-AI Summary

Apellis (Nasdaq: APLS) announced that NEJM published positive Phase 3 VALIANT results for EMPAVELI (pegcetacoplan) in C3 glomerulopathy (C3G) and primary IC-MPGN at Week 26.

Key results: 68% proteinuria reduction versus placebo (p<0.0001); eGFR stabilization +6.3 mL/min/1.73 m2 versus placebo (nominal p=0.03); and 71% of treated patients achieved zero C3 staining. EMPAVELI showed a favorable safety profile consistent with prior experience and was FDA-approved July 28, 2025.

Positive

• Proteinuria -68% versus placebo (p<0.0001)
• eGFR +6.3 mL/min/1.73 m2 versus placebo (nominal p=0.03)
• 71% of treated patients achieved zero C3 staining
• FDA approval of EMPAVELI on July 28, 2025

Negative

• Common adverse reactions ≥10%: infusion site reactions, pyrexia, nasopharyngitis, influenza, cough, nausea
• European approval pending: EMA CHMP opinion expected before year-end

News Market Reaction

+2.86%

1 alert

+2.86% News Effect

On the day this news was published, APLS gained 2.86%, reflecting a moderate positive market reaction.

Data tracked by StockTitan Argus on the day of publication.

Key Figures

Proteinuria reduction: 68% eGFR difference: +6.3 mL/min/1.73 m2 Complete C3 clearance: 71% +2 more

5 metrics

Proteinuria reduction 68% Primary endpoint reduction in proteinuria vs placebo (p<0.0001) at Week 26

eGFR difference +6.3 mL/min/1.73 m2 Stabilization of kidney function vs placebo (nominal p=0.03)

Complete C3 clearance 71% EMPAVELI‑treated patients with zero C3 staining intensity

Patient experience 2,750 patient-years Clinical and real‑world exposure to EMPAVELI across indications

Age eligibility 12 and older FDA‑approved age range for C3G and primary IC‑MPGN treatment

Market Reality Check

Price: $21.75 Vol: Volume 1,805,127 is about...

normal vol

$21.75 Last Close

Volume Volume 1,805,127 is about in line with recent activity, at 0.8x the 20‑day average 2,266,253. normal

Technical Shares at 24.965 are trading above the 200‑day MA of 21.92, reflecting an improved trend before this news.

Peers on Argus

APLS gained 3.78% while key biotech peers were mixed: SRRK +3.86%, IMVT +5.75%, ...

1 Up

APLS gained 3.78% while key biotech peers were mixed: SRRK +3.86%, IMVT +5.75%, KYMR -3.23%, TLX +0.43%, PTGX +0.26%, suggesting a company‑specific reaction to positive trial data.

Historical Context

5 past events · Latest: Dec 03 (Positive)

Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Dec 03	Clinical trial results	Positive	+2.9%	NEJM publication of positive Phase 3 VALIANT EMPAVELI results in C3G and IC‑MPGN.
Nov 25	Investor conferences	Neutral	+4.3%	Announcement of upcoming participation in Citi and Evercore healthcare conferences.
Nov 12	Clinical data update	Positive	+2.6%	Five‑year GALE data showing SYFOVRE delayed GA progression with consistent safety.
Nov 05	Investor conference	Neutral	-2.5%	Stifel Healthcare Conference presentation announcement with webcast and replay details.
Oct 30	Quarterly earnings	Positive	-31.0%	Profitable Q3 with $458.6M revenue and strong collaboration and product contributions.

Pattern Detected

Recent clinically focused announcements, including EMPAVELI and SYFOVRE data, were followed by positive price moves, while the Q3 2025 earnings release coincided with a sharp decline.

Recent Company History

Over the last few months, Apellis reported several major milestones. On Oct 30, 2025, Q3 results showed total revenue of $458.6M, driven by SYFOVRE and EMPAVELI, but the stock fell 31.01%. Subsequent conference participation in November had modest, mixed price effects. Positive GALE five‑year SYFOVRE data on Nov 12 and today’s NEJM publication of Phase 3 VALIANT results for EMPAVELI in C3G and IC‑MPGN both coincided with share gains, reinforcing the market’s focus on clinical and commercial execution.

Market Pulse Summary

This announcement highlighted NEJM publication of Phase 3 VALIANT data for EMPAVELI, showing a 68% p...

Analysis

This announcement highlighted NEJM publication of Phase 3 VALIANT data for EMPAVELI, showing a 68% proteinuria reduction, a +6.3 mL/min/1.73 m2 eGFR benefit, and 71% complete C3 clearance alongside favorable safety. It followed earlier one‑year VALIANT results and the July 2025 FDA approval for C3G and IC‑MPGN in patients 12+. Investors may track real‑world uptake, future regulatory decisions in Europe, and how these kidney indications contribute alongside SYFOVRE and broader financial performance.

Key Terms

phase 3, c3 glomerulopathy, immune complex membranoproliferative glomerulonephritis, adverse reactions, +3 more

7 terms

phase 3 medical

"published positive results from the Phase 3 VALIANT study investigating EMPAVELI"

Phase 3 is the late-stage clinical testing step for a new drug or medical treatment, where the product is given to large groups of patients to confirm effectiveness, monitor side effects, and compare it to standard care. Successful Phase 3 results are often the final scientific hurdle before regulators decide on approval and market launch—like passing a final exam before graduation—and can sharply change a company's valuation and future revenue prospects.

c3 glomerulopathy medical

"for C3 glomerulopathy (C3G) and primary immune complex membranoproliferative"

A rare kidney disease caused by abnormal activation of the body’s complement system that damages the tiny filters in the kidney, leading to blood and protein in the urine and progressive loss of kidney function. Investors watch it because it creates a defined but small market for diagnostics, drugs, and potential long-term treatment revenues, and trial results, approvals, or safety findings can sharply affect the valuations of companies developing therapies—think of it as a targeted repair market for a malfunctioning water filter in the body.

immune complex membranoproliferative glomerulonephritis medical

"primary immune complex membranoproliferative glomerulonephritis (IC-MPGN), which are severe"

A type of kidney inflammation where immune molecules form clumps that stick in and damage the tiny filters in the kidney, causing blood and protein to leak into urine and reducing the organ’s ability to clean the blood. Investors should care because prevalence, treatment options, and clinical trial results for therapies can materially affect healthcare costs, drug company valuations, regulatory decisions, and potential market opportunities in nephrology.

adverse reactions medical

"The most common adverse reactions in VALIANT (≥10%) were infusion site reactions"

Adverse reactions are harmful or unintended effects people experience after using a medicine, vaccine, medical device, or treatment; think of them as unexpected problems that show up when a product is used as intended. Investors care because these reactions can trigger regulatory warnings, safety reviews, recalls, reduced sales, or legal costs—similar to how widespread product defects can damage a company’s reputation and future earnings.

meningococcal infection medical

"there have been zero cases of meningococcal infection due to encapsulated bacteria"

Meningococcal infection is a serious bacterial illness that can inflame the protective layers around the brain and spinal cord or enter the bloodstream, often progressing rapidly and sometimes causing long-term disability or death; think of it as an aggressive infection attacking the body’s protective “shield.” It matters to investors because demand for vaccines, treatments, diagnostics, and public-health responses can create sudden regulatory decisions, shifting revenue prospects and risk for healthcare and biotech companies.

pivotal trial medical

"This marks the first time pivotal trial results for a C3G or primary IC-MPGN"

A pivotal trial is a key test of a new medicine or treatment to see if it works and is safe enough to be approved by health authorities. It's like a final exam for a new product, and passing it is essential for bringing the treatment to the public.

placebo medical

"68% (p<0.0001) proteinuria reduction in EMPAVELI-treated patients compared to placebo"

A placebo is an inactive pill, injection or procedure that looks and feels like the real treatment but contains no therapeutic ingredient, often called a sugar pill. Investors care because comparing a drug to a placebo reveals whether observed benefits come from the medicine itself or from expectation; clear superiority over placebo reduces regulatory and commercial risk, much like a blind taste test proves a new recipe really tastes better.

AI-generated analysis. Not financial advice.

• Robust and clinically meaningful benefits across all three key markers of disease – 68% reduction in proteinuria, stabilization of kidney function, and substantial clearance of C3 deposits
  
• Consistent results across adolescent and adult patients with C3G and primary IC-MPGN, including patients with C3G recurring after transplant
  
• EMPAVELI is the first FDA-approved treatment for C3G and primary IC-MPGN patients 12 and older
  

WALTHAM, Mass., Dec. 03, 2025 (GLOBE NEWSWIRE) -- Apellis Pharmaceuticals, Inc. (Nasdaq: APLS) today announced that The New England Journal of Medicine (NEJM) published positive results from the Phase 3 VALIANT study investigating EMPAVELI^® (pegcetacoplan) for C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN), which are severe and rare kidney diseases.

“The positive data published in the New England Journal of Medicine underscore the unprecedented benefits of EMPAVELI across all three key markers of disease,” said Carla Nester, M.D., MSA, FASN, senior author, professor of internal medicine and pediatrics and director of pediatric nephrology, University of Iowa Stead Family Children's Hospital. “C3G and primary IC-MPGN often lead to kidney failure, and the need for a kidney transplant or dialysis can be devastating. EMPAVELI represents a significant advance in treatment, and I’m thrilled that patients now have access to this important medicine.”  

The data published in NEJM highlight the positive Phase 3 VALIANT results at Week 26, which were consistent across adolescent and adult patients with C3G and primary IC-MPGN, including patients with C3G recurring after transplant. EMPAVELI demonstrated 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, with a difference of +6.3 mL/min/1.73 m² 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. 
  

“This marks the first time pivotal trial results for a C3G or primary IC-MPGN treatment have been featured in this leading medical journal,” said Peter Hillmen, M.B., Ch.B., Ph.D., chief medical advisor, rare disease, Apellis. “The results show that EMPAVELI has the potential to be life-changing for patients, regardless of their disease type, age, or transplant status. Following the recent FDA approval of EMPAVELI, we are encouraged by the strong response from the nephrology community and growing number of patients starting treatment, and we remain focused on reaching more people living with C3G and primary IC-MPGN.”

EMPAVELI showed favorable safety and tolerability in the VALIANT study, consistent with its established profile. The most common adverse reactions in VALIANT (≥10%) were infusion site reactions, pyrexia, nasopharyngitis, influenza, cough, and nausea. Across more than 2,750 patient-years of clinical and real-world experience with EMPAVELI in all approved indications, there have been zero cases of meningococcal infection due to encapsulated bacteria reported to date.

Results from the VALIANT study at one year were recently presented at the European Renal Association Congress and ASN Kidney Week, showing sustained improvements in key markers of disease as well as favorable safety and tolerability.

EMPAVELI was approved by the U.S. Food and Drug Administration on July 28, 2025. In the European Union, Apellis’ partner, Sobi®, expects an opinion by the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) before year-end.

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.^1-3 Additionally, approximately 90% of patients who previously received a kidney transplant will experience disease recurrence.⁴ The diseases are estimated to affect 5,000 people in the United States and up to 8,000 in Europe.⁵ 

About the VALIANT Study
The VALIANT Phase 3 study (NCT05067127) was a randomized, placebo-controlled, double-blinded, multi-center study that evaluated the efficacy and safety of EMPAVELI® (pegcetacoplan) 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 or 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^® (pegcetacoplan)
EMPAVELI^® (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 the first treatment approved in the United States for C3 glomerulopathy (C3G) or primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) in patients 12 years of age or older, to reduce proteinuria. EMPAVELI/Aspaveli® is also approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in the United States, European Union, and other countries globally. EMPAVELI is being evaluated for the treatment of additional 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 the Apellis and Sobi Collaboration
Apellis and Sobi have global co-development rights for systemic pegcetacoplan. Sobi has exclusive ex-U.S. commercialization rights for systemic pegcetacoplan, and Apellis has exclusive U.S. commercialization rights for systemic pegcetacoplan and worldwide commercial rights for ophthalmological pegcetacoplan, including for geographic atrophy.

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
media@apellis.com
617.420.4839

Investors: 
Eva Stroynowski
eva.stroynowski@apellis.com
617.938.6229

References
1. Smith RJH, et al. Nat Rev Nephrol. 2019;15(3):129-143.
2. Servais A, et al. Kidney Int. 2012;82(4):454-464.
3. Zand L, et al. J Am Soc Nephrol. 2014;25(5):1110-1117.
4. 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.
5. Data on file using literature consensus. 

FAQ

What did Apellis (APLS) report in the NEJM publication for EMPAVELI on December 3, 2025?

The NEJM published VALIANT Week 26 results showing 68% proteinuria reduction, eGFR +6.3 mL/min/1.73 m2, and 71% zero C3 staining in EMPAVELI-treated patients.

How did EMPAVELI perform on kidney function in the VALIANT Phase 3 trial for APLS?

EMPAVELI-treated patients showed stabilization of eGFR with a +6.3 mL/min/1.73 m2 difference versus placebo (nominal p=0.03) at Week 26.

What is the safety profile reported for EMPAVELI in the VALIANT study (APLS)?

VALIANT reported favorable safety consistent with prior data; most common adverse reactions (≥10%) included infusion site reactions, pyrexia, nasopharyngitis, influenza, cough, and nausea.

When was EMPAVELI approved by the FDA and who is eligible?

EMPAVELI was approved by the FDA on July 28, 2025 for patients with C3G and primary IC-MPGN aged 12 and older.

Did VALIANT include transplant patients and adolescents in the APLS trial population?

Yes; VALIANT results were consistent across adolescent and adult patients, including patients with C3G recurring after transplant.

What regulatory milestone is pending in Europe for EMPAVELI (APLS)?

Apellis’ partner Sobi expects an EMA CHMP opinion before year-end regarding EU approval.