Biogen Publishes Adolescent Data From Phase 3 VALIANT Study of EMPAVELI

Study Results Show Reduced Proteinuria in Adolescents With Rare Kidney Diseases

Biogen Inc. has announced the publication of results from a prespecified adolescent subgroup analysis of its Phase 3 VALIANT study evaluating EMPAVELI (pegcetacoplan).

The findings were published in the Clinical Journal of the American Society of Nephrology (CJASN). The adolescent analysis was previously presented at the 2025 Annual Meeting of the European Society of Paediatric Nephrology.

The analysis looked at adolescents between 12 and 17 years old who had either C3 glomerulopathy, known as C3G, or primary immune complex membranoproliferative glomerulonephritis, known as primary IC-MPGN.

According to the results, adolescents treated with EMPAVELI experienced meaningful reductions in proteinuria and stabilization of kidney function compared with those who received placebo.

What Did the Adolescent Analysis Show?

The adolescent subgroup included 55 patients.

At Week 26, adolescents receiving EMPAVELI had a 75% relative reduction in proteinuria compared with placebo. The 95% confidence interval was 59% to 84%, with a nominal p-value of less than 0.001.

Proteinuria means having too much protein in the urine. It can be a sign that the kidneys are not working properly.

The reduction in proteinuria was seen as early as Week 4 and continued through Week 26.

The study also found that 71% of adolescents treated with EMPAVELI achieved at least a 50% reduction in proteinuria. This compared with 4% of adolescents receiving placebo.

Another finding looked at both proteinuria and kidney function. About 57% of adolescents receiving EMPAVELI achieved stable kidney function along with at least a 50% reduction in proteinuria, compared with 4% in the placebo group.

Results Were Similar to the Overall VALIANT Population

The findings from adolescents were consistent with the results seen in the broader VALIANT study population.

Adolescents made up nearly half of the total study population.

This gave researchers one of the larger randomized datasets available for studying C3G and primary IC-MPGN in this age group.

The consistency between the adolescent subgroup and the overall study population was highlighted by Biogen as supporting the use of EMPAVELI in younger patients covered by its current US indication.

Why These Kidney Diseases Matter in Children

C3G and primary IC-MPGN are rare kidney diseases caused by problems involving the complement system.

The complement system is part of the body's immune system. When it becomes overactive, it can damage healthy tissue, including the kidneys.

Both diseases can cause ongoing kidney damage and may eventually lead to kidney failure.

These conditions can start early in life.

Around half of people with C3G are diagnosed before they reach 18 years of age. For primary IC-MPGN, the median age at diagnosis is approximately 21 years.

According to the information provided by Biogen, around 20% of children with C3G or primary IC-MPGN progress to kidney failure within 10 to 15 years after diagnosis despite standard treatment.

What Is Proteinuria?

Proteinuria is one of the important signs doctors monitor in kidney disease.

Healthy kidneys normally prevent large amounts of protein from passing into the urine.

When the kidney's filtering system is damaged, protein can leak into the urine.

A reduction in proteinuria can therefore be an important measure when studying treatments for kidney diseases such as C3G and primary IC-MPGN.

In the VALIANT adolescent analysis, researchers saw substantial reductions in proteinuria among patients receiving EMPAVELI.

EMPAVELI Is a Targeted Complement C3 Therapy

EMPAVELI is a targeted C3 therapy.

C3 is an important protein within the complement system. When complement activity becomes excessive, it can contribute to inflammation and tissue damage.

EMPAVELI is designed to regulate this excessive complement activation.

In the United States, EMPAVELI is indicated for adults and children aged 12 years and older with C3G or primary IC-MPGN to reduce proteinuria and the loss of kidney function.

The medicine is also approved for adults with paroxysmal nocturnal hemoglobinuria, or PNH.

FDA Expanded the EMPAVELI Label

The publication of the adolescent results follows a recent expansion of the US FDA-approved label for EMPAVELI.

Biogen says the label expansion makes EMPAVELI the first and only therapy approved in the United States to reduce both proteinuria and the loss of kidney function in adults and adolescents aged 12 years and older with C3G or primary IC-MPGN.

The label update was based on 52-week efficacy and safety data from the VALIANT study.

Those data showed reductions in proteinuria and continued preservation of kidney function, measured using estimated glomerular filtration rate, or eGFR.

eGFR is a commonly used measure that estimates how well the kidneys are filtering waste from the blood.

How the VALIANT Study Was Designed

VALIANT is a Phase 3 randomized, placebo-controlled, double-blind, multicenter clinical study.

The trial included 124 patients aged 12 years and older with C3G or primary IC-MPGN.

The study included both adolescents and adults.

Participants could have kidney disease affecting their native kidneys or disease that had returned following a kidney transplant.

Patients were randomly assigned to receive either EMPAVELI or placebo.

Treatment was given twice a week for 26 weeks.

After this initial period, participants entered a 26-week open-label period during which all patients received EMPAVELI.

The primary endpoint was the change in urine protein-to-creatinine ratio, or UPCR, at Week 26 compared with baseline.

EMPAVELI Was Well Tolerated in Adolescents

The company reported that EMPAVELI was well tolerated among the adolescent patients included in the analysis.

The safety profile in adolescents was consistent with the overall VALIANT population.

However, EMPAVELI carries important safety risks because it affects the complement system.

The medicine has a boxed warning about serious infections caused by encapsulated bacteria.

Important Infection Risk With EMPAVELI

Because EMPAVELI is a complement inhibitor, it can increase the risk of serious infections.

The most important infections highlighted in the prescribing information are those caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type B.

These infections can become life-threatening or fatal if they are not identified and treated quickly.

Patients are generally required to complete or update recommended vaccinations against these bacteria at least two weeks before starting EMPAVELI, unless delaying treatment creates a greater risk.

Vaccination does not completely remove the risk of serious infection.

Patients receiving EMPAVELI need to be monitored for signs and symptoms of serious infections and should receive immediate medical evaluation if an infection is suspected.

EMPAVELI Is Available Through a REMS Program

Because of the infection risk, EMPAVELI is available in the United States only through a restricted Risk Evaluation and Mitigation Strategy, known as the EMPAVELI REMS.

Under this program, prescribers must be enrolled and certified.

They must also counsel patients about the risk of serious infections and provide required educational materials.

Pharmacies that dispense EMPAVELI must also be certified under the program.

The REMS requirements are intended to help healthcare professionals and patients understand and manage the infection risk associated with complement inhibition.

Other Safety Information

EMPAVELI can also cause infusion-related reactions and systemic hypersensitivity reactions.

Reported reactions can include facial swelling, rash, hives and fever. Severe reactions, including anaphylaxis, have also been reported.

If a severe hypersensitivity reaction occurs, treatment should be stopped and appropriate medical care provided.

The most common adverse reactions in adults and pediatric patients aged 12 years and older with C3G or primary IC-MPGN include infusion-site reactions, fever, nasopharyngitis, influenza, cough and nausea.

EMPAVELI can also interfere with certain laboratory coagulation tests using silica reagents, potentially causing an artificially prolonged activated partial thromboplastin time.

Reproductive Health Considerations

The prescribing information also includes precautions for females of reproductive potential.

EMPAVELI may cause embryo-fetal harm when given during pregnancy.

Pregnancy testing is recommended before treatment for females of reproductive potential.

Patients in this group are advised to use effective contraception during treatment and for 40 days after the last dose.

What the Researchers Said

Bradley Dixon, M.D., Section Chief of Pediatric Nephrology and Professor of Pediatrics at the University of Colorado School of Medicine and Children's Hospital Colorado, said C3G and primary IC-MPGN are often diagnosed early in life.

He said preventing progressive kidney damage can have a long-term impact for these patients.

Dixon also said the VALIANT results showed substantial reductions in proteinuria and stabilization of kidney function in adolescents, consistent with findings from the broader study population.

Daniel Jones, Ph.D., vice president and head of global medical affairs for EMPAVELI at Biogen, said the published findings strengthen the company's confidence in the potential benefits of EMPAVELI for adolescents living with C3G and primary IC-MPGN.

What Happens Next?

The VALIANT data are now part of the clinical evidence supporting EMPAVELI's use in patients aged 12 years and older with C3G and primary IC-MPGN in the United States.

The published adolescent analysis adds more detail about how the treatment performed in younger patients within the Phase 3 study.

Biogen will continue to evaluate EMPAVELI as part of its broader kidney disease and complement-focused development work.

About Biogen

Biogen is a biotechnology company founded in 1978.

The company develops medicines using research into human biology and different treatment approaches.

Its research and development programs cover several areas of serious disease, including neurological and immune-related conditions.

EMPAVELI is part of Biogen's portfolio of medicines targeting complement-related disease.

For patients with C3G and primary IC-MPGN, the company is focused on the use of EMPAVELI to reduce proteinuria and slow the loss of kidney function in adults and adolescents aged 12 years and older.