ULTOMIRIS® (ravulizumab-cwvz) demonstrated 43.4% reduction in proteinuria vs placebo in adults with immunoglobulin A nephropathy at 34 weeks in I CAN Phase III trial

PUBLISHED 6 June 2026

ULTOMIRIS^® (ravulizumab-cwvz) demonstrated 43.4% reduction in proteinuria
vs placebo in adults with immunoglobulin A nephropathy at 34 weeks in I CAN
Phase III trial

Rapid reduction in proteinuria observed as early as week 10 and sustained through
week 34, supporting potential of ULTOMIRIS as a disease-modifying treatment

Results showed treatment effect consistent across subgroups

Positive results from a prespecified interim analysis of the I CAN Phase III trial evaluating ULTOMIRIS^® (ravulizumab-cwvz) demonstrated a statistically significant and clinically meaningful reduction in proteinuria from baseline, based on 24-hour urine protein creatinine ratio (UPCR), compared to placebo at week 34 in adults with immunoglobulin A nephropathy (IgAN) who are at risk of disease progression.¹

ULTOMIRIS demonstrated a 46.6% reduction in 24-hour UPCR from baseline (95% confidence interval [CI]: 39.0%, 53.2%) at week 34, compared to 5.6% (95% CI: -4.9%, 15.0%) in patients receiving placebo, resulting in a placebo-adjusted treatment effect of 43.4% (95% CI: 33.5%, 51.8%; p<0.0001).¹

The reduction in proteinuria was rapid, observed as early as week 10 with ULTOMIRIS (36.7% [95% CI: 30.2%, 42.6%]) and sustained through 34 weeks, compared to placebo (8.5% [95% CI: 0.5%, 15.8%]). These results were consistent across patient subgroups, reflecting diverse demographic and baseline clinical characteristics and disease severity.¹

Jonathan Barratt, MD, Mayer Professor of Renal Medicine, University of Leicester, United Kingdom, and I CAN trial investigator, said: "For patients with IgAN, terminal complement activation is a key driver of inflammation and progressive loss of kidney function, which can frequently result in end-stage kidney disease. These interim results show that by targeting the terminal complement pathway, ULTOMIRIS delivered a rapid and significant reduction in proteinuria supporting its potential as a disease-modifying treatment for people living with this devastating rare disease."

Gianluca Pirozzi, Senior Vice President, Head of Development, Regulatory and Safety, Alexion, AstraZeneca Rare Disease, said: "These interim data demonstrate an early and significant reduction in proteinuria with benefit seen across subgroups, including patients who are at higher risk of disease progression. Results underscore the important role of terminal complement inhibition in treating IgAN and highlight the potential of ULTOMIRIS as a meaningful new treatment to address the unmet needs of this patient population. We look forward to advancing regulatory filings for approval in key markets, based on these interim data."

Primary endpoint (interim analysis): Week 34 Change from Baseline in 24-hour UPCR¹

Change in 24-Hour UPCR Over Time¹

The safety profile observed in this trial was consistent with the known profile of ULTOMIRIS and generally well tolerated, with no new safety concerns identified.¹ The most common adverse events (AE) reported were upper respiratory tract infection (11.3%), nasopharyngitis (9.2%) and infusion-related reactions (8.4%) in those treated with ULTOMIRIS; and upper respiratory tract infection (10.2%), nasopharyngitis (9.0%) and hypertension (6.6%) in those receiving placebo.¹

These results were presented today at the 63^rd European Renal Association (ERA) Congress in Glasgow, Scotland.

The trial's primary endpoint of change from baseline in estimated glomerular filtration rate (eGFR) will be measured at week 106.²

INDICATION(S) & IMPORTANT SAFETY INFORMATION

INDICATION(S)

Paroxysmal Nocturnal Hemoglobinuria (PNH)

ULTOMIRIS is indicated for the treatment of adult and pediatric patients one month of age and older with paroxysmal nocturnal hemoglobinuria (PNH).

Atypical Hemolytic Uremic Syndrome (aHUS)

ULTOMIRIS is indicated for the treatment of adult and pediatric patients one month of age and older with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA).

Limitation of Use:

ULTOMIRIS is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).

Generalized Myasthenia Gravis (gMG)

ULTOMIRIS is indicated for the treatment of adult patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive.

Neuromyelitis Optica Spectrum Disorder (NMOSD)

ULTOMIRIS is indicated for the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive.

IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS MENINGOCOCCAL INFECTIONS ULTOMIRIS, a complement inhibitor, increases the risk of serious infections caused by Neisseria meningitidis [see Warnings and Precautions (5.1)] Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early. 1. Complete or update vaccination for meningococcal bacteria (for serogroups A, C, W, Y, and B) at least 2 weeks prior to the first dose of ULTOMIRIS, unless the risks of delaying ULTOMIRIS therapy outweigh the risk of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against meningococcal bacteria in patients receiving a complement inhibitor. See Warnings and Precautions (5.1) for additional guidance on the management of the risk of serious infections caused by meningococcal bacteria. 2. Patients receiving ULTOMIRIS are at increased risk for invasive disease caused by Neisseria meningitidis, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious meningococcal infections and evaluate immediately if infection is suspected. Because of the risk of serious meningococcal infections, ULTOMIRIS is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called ULTOMIRIS and SOLIRIS REMS [see Warnings and Precautions (5.2)].

CONTRAINDICATIONS

- Initiation in patients with unresolved serious Neisseria meningitidis infection.

WARNINGS AND PRECAUTIONS

Serious Meningococcal Infections

ULTOMIRIS, a complement inhibitor, increases a patient's susceptibility to serious, life-threatening, or fatal infections caused by meningococcal bacteria (septicemia and/or meningitis) in any serogroup, including non-groupable strains. Life-threatening and fatal meningococcal infections have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors.

Revaccinate patients in accordance with ACIP recommendations considering the duration of ULTOMIRIS therapy. 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 ULTOMIRIS therapy is indicated in a patient who is not up to date with meningococcal vaccines according to ACIP recommendations, provide antibacterial drug prophylaxis and administer meningococcal vaccines as soon as possible. Various durations and regimens of antibacterial drug prophylaxis have been considered, but the optimal durations and drug regimens for prophylaxis and their efficacy have not been studied in unvaccinated or vaccinated patients receiving complement inhibitors, including ULTOMIRIS. The benefits and risks of treatment with ULTOMIRIS, as well as those associated with antibacterial drug prophylaxis in unvaccinated or vaccinated patients, must be considered against the known risks for serious infections caused by Neisseria meningitidis.

Vaccination does not eliminate the risk of serious meningococcal infections, despite development of antibodies following vaccination.

Closely monitor patients for early signs and symptoms of meningococcal infection and evaluate patients immediately if infection is suspected. Inform patients of these signs and symptoms and instruct patients to seek immediate medical care if they occur. Promptly treat known infections. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Consider interruption of ULTOMIRIS in patients who are undergoing treatment for serious meningococcal infection depending on the risks of interrupting treatment in the disease being treated.

ULTOMIRIS and SOLIRIS REMS

Due to the risk of serious meningococcal infections, ULTOMIRIS is available only through a restricted program called ULTOMIRIS and SOLIRIS REMS.

Prescribers must enroll in the REMS, counsel patients about the risk of serious meningococcal infection, provide patients with the REMS educational materials, assess patient vaccination status for meningococcal vaccines (against serogroups A, C, W, Y, and B) and vaccinate if needed according to current ACIP recommendations two weeks prior to the first dose of ULTOMIRIS. Antibacterial drug prophylaxis must be prescribed if treatment must be started urgently, and the patient is not up to date with both meningococcal vaccines according to current ACIP recommendations at least two weeks prior to the first dose of ULTOMIRIS. Patients must receive counseling about the need to receive meningococcal vaccines and to take antibiotics as directed, signs and symptoms of meningococcal infection, and be instructed to carry the Patient Safety Card at all times during and for 8 months following ULTOMIRIS treatment.

Further information is available at https://www.UltSolREMS.com or 1-888-765-4747.

Other Infections

Serious infections with Neisseria species (other than Neisseria meningitidis), including disseminated gonococcal infections, have been reported.

ULTOMIRIS blocks terminal complement activation; therefore, patients may have increased susceptibility to infections, especially with encapsulated bacteria, such as infections caused by Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent, Neisseria gonorrhoeae. Children treated with ULTOMIRIS may be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). Administer vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) infections according to ACIP recommendations. Patients receiving ULTOMIRIS are at increased risk for infections due to these organisms, even if they develop antibodies following vaccination.

Monitoring Disease Manifestations after ULTOMIRIS Discontinuation

Treatment Discontinuation for PNH

After discontinuing treatment with ULTOMIRIS, closely monitor for signs and symptoms of hemolysis, identified by elevated LDH along with sudden decrease in PNH clone size or hemoglobin, or re-appearance of symptoms such as fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction. Monitor any patient who discontinues ULTOMIRIS for at least 16 weeks to detect hemolysis and other reactions. If signs and symptoms of hemolysis occur after discontinuation, including elevated LDH, consider restarting treatment with ULTOMIRIS.

Treatment Discontinuation for aHUS

ULTOMIRIS treatment of aHUS should be a minimum duration of 6 months. Due to heterogeneous nature of aHUS events and patient-specific risk factors, treatment duration beyond the initial 6 months should be individualized. There are no specific data on ULTOMIRIS discontinuation. After discontinuing treatment with ULTOMIRIS, patients should be monitored for clinical symptoms and laboratory signs of TMA complications for at least 12 months. TMA complications post-discontinuation can be identified if any of the following is observed: Clinical symptoms of TMA include changes in mental status, seizures, angina, dyspnea, thrombosis or increasing blood pressure. In addition, at least two of the following laboratory signs observed concurrently and results should be confirmed by a second measurement 28 days apart with no interruption: a decrease in platelet count of 25% or more as compared to either baseline or to peak platelet count during ULTOMIRIS treatment; an increase in serum creatinine of 25% or more as compared to baseline or to nadir during ULTOMIRIS treatment; or, an increase in serum LDH of 25% or more as compared to baseline or to nadir during ULTOMIRIS treatment. If TMA complications occur after discontinuation, consider reinitiation of ULTOMIRIS treatment or appropriate organ-specific supportive measures.

Thromboembolic Event Management

The effect of withdrawal of anticoagulant therapy during treatment with ULTOMIRIS has not been established. Treatment should not alter anticoagulant management.

Infusion-Related Reactions

Administration of ULTOMIRIS may result in systemic infusion-related reactions, including anaphylaxis and hypersensitivity reactions. In clinical trials, infusion-related reactions occurred in approximately 1 to 7% of patients, including lower back pain, abdominal pain, muscle spasms, drop or elevation in blood pressure, rigors, limb discomfort, drug hypersensitivity (allergic reaction), and dysgeusia (bad taste). These reactions did not require discontinuation of ULTOMIRIS. If signs of cardiovascular instability or respiratory compromise occur, interrupt ULTOMIRIS and institute appropriate supportive measures.

ADVERSE REACTIONS

Adverse Reactions for PNH

Adverse reactions reported in ≥10% or more of patients with PNH were upper respiratory tract infection and headache. Serious adverse reactions were reported in 15 (6.8%) patients receiving ULTOMIRIS. The serious adverse reactions in patients treated with ULTOMIRIS included hyperthermia and pyrexia. No serious adverse reaction was reported in more than 1 patient treated with ULTOMIRIS. One fatal case of sepsis was identified in a patient treated with ULTOMIRIS. In clinical studies, clinically relevant adverse reactions in 1% of adult patients include infusion-related reactions.

Adverse reactions reported in ≥10% of pediatric patients treated with ULTOMIRIS who were treatment-naïve vs. Eculizumab-experienced were anemia (20% vs. 25%), abdominal pain (0% vs. 38%), constipation (0% vs. 25%), pyrexia (20% vs. 13%), upper respiratory tract infection (20% vs. 75%), pain in extremity (0% vs. 25%), and headache (20% vs. 25%).

Adverse Reactions for aHUS

Most common adverse reactions in patients with aHUS (incidence ≥20%) were upper respiratory tract infection, diarrhea, nausea, vomiting, headache, hypertension and pyrexia. Serious adverse reactions were reported in 42 (57%) patients with aHUS receiving ULTOMIRIS. The most frequent serious adverse reactions reported in more than 2 patients (2.7%) treated with ULTOMIRIS were hypertension, pneumonia and abdominal pain.

Adverse reactions reported in ≥20% of pediatric patients treated with ULTOMIRIS were diarrhea, constipation, vomiting, pyrexia, upper respiratory tract infection, decreased vitamin D, headache, cough, rash, and hypertension.

Adverse Reactions for gMG

Most common adverse reactions in adult patients with gMG (incidence ≥10%) were diarrhea and upper respiratory tract infection. Serious adverse reactions were reported in 20 (23%) of patients treated with ULTOMIRIS and in 14 (16%) patients receiving placebo. The most frequent serious adverse reactions were infections reported in at least 8 (9%) patients treated with ULTOMIRIS and in 4 (4%) patients treated with placebo. Of these infections, one fatal case of COVID-19 pneumonia was identified in a patient treated with ULTOMIRIS and one case of infection led to discontinuation of ULTOMIRIS.

Adverse Reactions for NMOSD

Most common adverse reactions in adult patients with NMOSD (incidence ≥10%) were COVID-19, headache, back pain, arthralgia, and urinary tract infection. Serious adverse reactions were reported in 8 (13.8%) patients with NMOSD receiving ULTOMIRIS.

DRUG INTERACTIONS

Plasma Exchange, Plasmapheresis, and Intravenous Immunoglobulins

Concomitant use of ULTOMIRIS with plasma exchange (PE), plasmapheresis (PP), or intravenous immunoglobulin (IVIg) treatment can reduce serum ravulizumab concentrations and requires a supplemental dose of ULTOMIRIS.

Neonatal Fc Receptor Blockers

Concomitant use of ULTOMIRIS with neonatal Fc receptor (FcRn) blockers (e.g., efgartigimod) may lower systemic exposures and reduce effectiveness of ULTOMIRIS. Closely monitor for reduced effectiveness of ULTOMIRIS.

USE IN SPECIFIC POPULATIONS

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ULTOMIRIS during pregnancy. Healthcare providers and patients may call 1-833-793-0563 or go to https://www.UltomirisPregnancyStudy.com to enroll in or to obtain information about the registry.

To report SUSPECTED ADVERSE REACTIONS, contact Alexion Pharmaceuticals, Inc. at 1-844-259-6783 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see accompanying full Prescribing Information for ULTOMIRIS, including Boxed WARNING regarding serious and life-threatening or fatal meningococcal infections.

Notes

Immunoglobulin A Nephropathy (IgAN)

Immunoglobulin A nephropathy (IgAN) is a rare, inflammatory disease of the kidneys that can lead to chronic kidney disease (CKD) and progress to end-stage kidney disease (ESKD). It begins when the body develops abnormal IgA proteins resulting in immune complexes that are deposited in the kidneys causing damage. The deposition of these complexes activates the complement system, leading to terminal complement-driven inflammation. This results in damage and loss of essential parts of the kidney, including cells in the glomeruli, the part of the kidneys that filters and cleans the blood. Over time, this damage impacts the ability of the kidneys to function properly, resulting in chronic kidney disease that can progress to end-stage kidney disease.³

The signs and symptoms of IgAN can include blood in the urine (hematuria), foamy urine (proteinuria), swelling in hands and feet (edema) and high blood pressure (hypertension).⁴ Most people with IgAN do not experience symptoms in the early stages of the disease, and therefore, it often goes undetected until it has progressed. At diagnosis, irreversible kidney damage may have already occurred.^5,6 Approximately half of people with IgAN who have elevated protein levels in urine or reduced kidney function are at-risk of progression to ESKD, or kidney failure, within 10 years of diagnosis.⁷

I CAN (ALXN1210-IgAN-320)

I CAN (ALXN1210-IgAN-320) is a global, Phase III, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of ULTOMIRIS in adults with immunoglobulin A nephropathy (IgAN) who are at risk of disease progression. Participants were on stable concomitant IgAN treatment(s) consistent with standard of care for at least three months prior to screening.²

Participants were randomized 1:1 to receive either ULTOMIRIS or placebo, administered intravenously for a total of 106 weeks. Patients in the treatment arm received a loading dose of ULTOMIRIS on Day 1, followed by regular weight-based maintenance dosing of ULTOMIRIS beginning on Day 15 and then every eight weeks through the 106-week blinded treatment period. Patients who completed the randomized control period had the option to enter an open-label access period.²

The primary endpoints are change from baseline in proteinuria based on 24-hour urine protein creatinine ratio (UPCR) at week 34 and change from baseline in estimated glomerular filtration rate (eGFR) at week 106, assessed at the interim analysis and final analysis, respectively. Key secondary endpoints for the final analysis include reduction in 24-hour UPCR ≥ 50% from baseline at week 34, change from baseline in proteinuria based on 24-hour UPCR at week 10, time to sustained ≥ 30% eGFR decline up to week 106 and time to first occurrence of composite kidney event up to week 106. The trial was designed to enroll approximately 510 participants from 28 countries across North America, South America, Europe, Asia and Australia.²

ULTOMIRIS^® (ravulizumab-cwvz)

ULTOMIRIS^® (ravulizumab-cwvz), the longest-acting C5 complement inhibitor, provides immediate, complete and sustained complement inhibition. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body's immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. Following a loading dose, ULTOMIRIS is administered intravenously every eight weeks in adults, or every four or eight weeks in pediatric patients (based on body weight).

ULTOMIRIS is approved in the US, EU, Japan and other countries for the treatment of certain adults with paroxysmal nocturnal hemoglobinuria (PNH) and is also approved for certain children with PNH in the US, EU and other countries.

ULTOMIRIS is also approved in the US, EU, Japan and other countries for the treatment of certain adults and children with atypical hemolytic uremic syndrome (aHUS).

Additionally, ULTOMIRIS is approved in the US, EU, Japan, China and other countries for the treatment of certain adults with generalized myasthenia gravis (gMG).

Further, ULTOMIRIS is approved in the US, EU, Japan, China and other countries for the treatment of certain adults with neuromyelitis optica spectrum disorder (NMOSD).

ULTOMIRIS is being assessed as a treatment for additional indications as part of a broad development program.

Alexion
Alexion, AstraZeneca Rare Disease, is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and delivery of life-changing medicines. A pioneering leader in rare disease for more than three decades, Alexion was the first to translate the complex biology of the complement system into transformative medicines, and today it continues to build a diversified pipeline across disease areas with significant unmet need, using an array of innovative modalities. As part of AstraZeneca, Alexion is continually expanding its global geographic footprint to serve more rare disease patients around the world. It is headquartered in Boston, US. For more information, please visit www.alexion.us.

AstraZeneca
AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Disease, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca-us.com and follow the Company on social media @AstraZeneca.

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References

1. Barratt J, et al. Ravulizumab in IgA nephropathy: a prespecified interim analysis of a randomized phase 3 trial (I CAN). Presented at European Renal Association (ERA) Congress; 2026 Jun 6; Glasgow, Scotland.

2. ClinicalTrials.gov. A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ravulizumab in Adult Participants With Immunoglobulin A Nephropathy (IgAN). NCT Identifier: NCT06291376. Available here. Accessed June 2026.

3. Cheung CK, et al. The pathogenesis of IgA nephropathy and implications for treatment. Nat Rev Nephrol. 2025;21(1):9-23. doi:10.1038/s41581-024-00885-3. Epub 2024 Sep 4.

4. Rajasekaran A, et al. IgA Nephropathy: An Interesting Autoimmune Kidney Disease. Am J Med Sci. 2021; 361(2):176-194.

5. Kidney Disease: Improving Global Outcomes (KDIGO) IgAN and IgAV Work Group, et al. KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV). Kidney Int. 2025; 108(4S): S1-S71.

6. Stamellou E, et al. IgA nephropathy. Nat Rev Dis Primers. 2023;9(1):67. doi:10.1038/s41572-023-00476-9.

Wong K, et al. Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort. Lancet. 2024;