Roche presents interim phase III data showing sefaxersen significantly reduced proteinuria in people with IgA nephropathy (IgAN)

2026-10-23

Sefaxersen achieved a statistically significant 43.1% reduction in proteinuria, a key indicator of kidney damage, relative to placebo at 37 weeks with consistent treatment effects across all prespecified patient subgroups¹
As the first antisense oligonucleotide (ASO) evaluated in IgAN, sefaxersen inhibits complement factor B production and has the potential to slow IgAN disease progression by reducing kidney inflammation²
Investigational sefaxersen is intended to be a once-monthly subcutaneous injection and designed to enable convenient self-administration at home³
Despite recent advances, many people with IgAN remain at risk of disease progression and kidney failure, highlighting the need for additional targeted treatment options for those who do not respond to initial therapy^4,5

Basel, 23 October 2026 - Roche (SIX: RO, ROP; OTCQX: RHHBY) announced today late-breaking oral presentation data from the ongoing phase III IMAgINATION study in adults with primary IgA nephropathy (IgAN) receiving optimised standard of care, demonstrating that investigational sefaxersen achieved a statistically significant and clinically meaningful 43.1% reduction in proteinuria (95% confidence interval [CI]: 32.5 - 52.0, P<0.0001), relative to placebo at 37 weeks, as measured by 24-hour urine protein-to-creatinine ratio (UPCR).¹ Proteinuria is a key indicator of kidney damage and a reduction in UPCR is strongly associated with the preservation of long-term kidney function.^6,7Results presented at the American Society of Nephrology (ASN) Kidney Week 2026 also showed that, among patients with baseline haematuria (blood in urine), a greater proportion of patients achieved haematuria resolution at Week 37 with sefaxersen versus placebo.¹

“These phase III results demonstrate the potential for sefaxersen to meaningfully reduce protein in the urine, a key indicator of kidney damage, in people with IgA nephropathy,” said Levi Garraway, MD, PhD, Roche's Chief Medical Officer and Head of Global Product Development. “By inhibiting complement factor B in the liver, sefaxersen may offer a novel approach to slow disease progression in IgAN, potentially helping patients delay or avoid long-term dialysis or kidney transplantation.”

The treatment effect in all prespecified subgroups was consistent with the clinically meaningful reductions in proteinuria shown in the primary endpoint results.¹ Sefaxersen was well tolerated with a safety profile consistent with the previously reported phase II study, exhibiting no new safety signals.^1,2

Sefaxersen is an investigational once-monthly subcutaneous injection designed to enable convenient self-administration for people with IgAN.³ The IMAgINATION study will continue as a blinded study to evaluate the change in kidney function over two years, as measured by estimated glomerular filtration rate (eGFR) at week 105. Data will be shared with health authorities, with the goal of bringing this treatment to patients as soon as possible.

Typically diagnosed before the age of 40, IgAN affects at least 25 adults per million worldwide each year.^8,9 IgAN, also known as Berger’s disease, is a chronic and progressive autoimmune disease that leads to end-stage kidney disease in up to 50% of patients within 20 years of diagnosis.^5,10 It is the most common form of primary glomerulonephritis (inflammation of the tiny filters, glomeruli, in the kidneys) and is a major cause of chronic kidney disease as well as kidney failure.⁸

About sefaxersen
Investigational sefaxersen is the first highly specific liver-directed antisense oligonucleotide (ASO) inhibitor of factor B production being evaluated in IgA nephropathy (IgAN).² Serum complement factor B levels are elevated in people with IgAN. When we reduce these levels, it in turn reduces the level of protein in urine, which is a key indicator of improved kidney function.^11,12

Sefaxersen is designed to provide sustained control of the alternative complement pathway, an important pathway in IgAN, enabling once-monthly subcutaneous dosing and is intended for self-administration in people with IgAN.³ In phase I and II trials, sefaxersen was shown to be generally well tolerated in healthy volunteers and people with IgAN who were at high risk of progression, and reduced proteinuria and plasma complement factor B.^2,13

Roche licensed sefaxersen from Ionis Pharmaceuticals for the treatment of complement mediated diseases.

About the IMAgINATION study
IMAgINATION [NCT05797610] is a phase III, multicentre, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of subcutaneous sefaxersen, an investigational antisense inhibitor of complement factor B, in patients with primary IgA nephropathy at high risk of progression.^1,14 The study enrolled 459 people, who are randomised 1:1 to receive sefaxersen or placebo for 105 weeks.^1,14 Participants may switch to open-label treatment after week 105 at the investigator's discretion or after the common-close timepoint, whichever occurs first.^1,14 The primary endpoint of the study is the change from baseline in the urine protein-to-creatinine ratio at 37 weeks.^1,14

About primary immunoglobulin A nephropathy (IgAN)
IgAN, also known as Berger’s disease, is a serious, chronic and progressive autoimmune kidney disease affecting at least 25 adults per million worldwide each year and is typically diagnosed before the age of 40 years.^8-10 In IgAN, immune complexes deposit in the kidneys, which activates the complement system’s alternative pathway, leading to inflammation and subsequent kidney damage.¹⁵ It is the most common form of primary glomerulonephritis (inflammation of kidney glomeruli) and remains a leading cause of kidney failure, with up to 50% of patients experiencing end-stage kidney disease within 20 years of diagnosis.^5,8 Many current therapies aim to reduce protein levels in the urine and control blood pressure to slow progression of the disease.¹⁶

Updated KDIGO 2025 guidelines* highlight the need to address both the underlying immune-mediated causes of IgAN and the downstream consequences of kidney damage.⁴ While new therapies have expanded treatment options, important unmet needs remain, including improved long-term preservation of kidney function and more targeted approaches that address key drivers of disease progression.^4,16

About Roche in Immunology
For over two decades, Roche has advanced immune system research, creating groundbreaking targeted treatments that have transformed care for people with blood disorders, neurological conditions and autoimmune diseases. With a development pipeline exploring more than 20 medical approaches, we are targeting widespread, complex conditions like chronic lung disease (COPD) and inflammatory bowel disease (IBD), alongside lupus and autoimmune kidney diseases. Our ultimate goal is to lessen the burden of chronic immune disorders on patients, healthcare systems, and society.

About Roche
Roche (SIX: RO, ROP; OTCQX: RHHBY) is a healthcare company uniquely placed to prevent, stop and cure diseases by uniting leading science and technology across diagnostics, medicines and digital solutions.

Roche was founded in Basel, Switzerland in 1896 and today is a leading provider of transformative medicines and diagnostics for millions of people in over 150 countries around the world. It is dedicated to tackling healthcare challenges that place the greatest strain on patients, families, communities and healthcare systems. Across its Diagnostics and Pharmaceutical divisions, Roche focuses on areas including oncology, neurology, cardiovascular and metabolic diseases, ophthalmology, infectious diseases and immunology with the aim of providing real and positive change for patients, the people they love and the professionals who care for them.

Genentech in the United States is a fully owned subsidiary in the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, a major innovator in the Japanese therapeutic antibody market.

For more information, please visit www.roche.com.

All trademarks used or mentioned in this release are protected by law.

*KDIGO guidelines serve as the foundational framework for healthcare organisations, policymakers, and clinicians worldwide to standardise kidney disease diagnosis, staging, and treatment.

References
[1] Barratt J., et al. Sefaxersen, a Novel mRNA-Targeted Therapy for IgA Nephropathy: Interim Analysis of the Phase 3 IMAgINATION Trial. Presented at: ASN Kidney Week; 2026 Oct 20-26; Denver, CO, USA. Abstract #FR-OR104.
[2] Barbour SJ, et al. A single-arm phase 2 trial of an investigational RNA therapeutic to complement factor B sefaxersen for treatment of IgA nephropathy. Kidney Int. 2026;109:592-601.
[3] Barratt J, et al. IMAGINATION: a global phase 3 trial of RO7434656, an antisense oligonucleotide inhibitor of complement factor B, in IgA nephropathy. Kidney Int Rep. 2024;9 Suppl. WCN24-912.
[4] Kidney Disease: Improving Global Outcomes (KDIGO) IgAN and IgAV Work Group. 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.
[5] Caster DJ, et al. Clinicopathological characteristics of adult IgA nephropathy in the United States. Kidney Int Rep. 2023;8:1792-1800.
[6] Longhitano E, et al. Proteinuria and Progression of Renal Damage: The Main Pathogenetic Mechanisms and Pharmacological Approach. Medicina (Kaunas). 2024 Nov 6;60(11):1821.
[7] Qin X, et al. Association Between Urinary Protein-to-Creatinine Ratio and Chronic Kidney Disease Progression: A Secondary Analysis of a Prospective Cohort Study. Front. Med. 2022; 9:854300.
[8] Pitcher D, et al. Long-term outcomes in IgA nephropathy. Clin J Am Soc Nephrol. 2023;18:727-738.
[9] McGrogan A, Franssen CF and de Vries CS. The incidence of primary glomerulonephritis worldwide: a systematic review of the literature. Nephrol Dial Transplant 2011; 26: 414-430.
[10] Cleveland Clinic. IgA Nephropathy [Internet; cited 2026 October 15]. Available from: https://my.clevelandclinic.org/health/diseases/5990-iga-nephropathy.
[11] Chiu YL, et al. Alternative complement pathway is activated and associated with galactose-deficient IgA. Front Immunol 2021; 12: 638309.
[12] Marques F, et al. Impact of early proteinuria reduction in glomerular disease and decline of kidney function: a retrospective cohort. J Clin Med. 2022;11(19):5968.
[13] McCaleb ML, et al. Inhibiting the alternative pathway of complement by reducing systemic complement factor B: Randomized, double-blind, placebo-controlled phase 1 studies with Sefaxersen. Immunobiology. 2025 Mar;230(2):152876.
[14] ClinicalTrials.gov. A Study to Evaluate RO7434656 in Participants With Immunoglobulin A Nephropathy (IgAN) (IMAGINATION) (NCT05797610) [Internet; cited 2026 Oct 15]. Available from: https://clinicaltrials.gov/study/NCT05797610.
[15] Wu MY, et al. The emerging role of pathogenesis of IgA nephropathy. J Clin Med. 2018;7:225.
[16] Floege J, et al. Current treatment of IgA nephropathy. Semin Immunopathol. 2021;43:717-728.

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