Positive interim data shows Roche’s sefaxersen significantly reduces proteinuria in people with IgA nephropathy (IgAN)

2026-09-23

In the phase III IMAgINATION study, sefaxersen demonstrated statistically significant and clinically meaningful reductions in proteinuria versus placebo at 37 weeks, showing best-in-class potential
Sefaxersen inhibits complement factor B production at its primary source in the liver, thus blocking a key driver of IgAN-related kidney damage¹
IgAN is a progressive kidney disease that is typically diagnosed in young adults and up to 50% of people progress to kidney failure within 20 years, requiring dialysis or transplantation^2-4
Interim data will be presented at an upcoming medical meeting and shared with health authorities

Basel, 23 September 2026 - Roche (SIX: RO, ROP; OTCQX: RHHBY) announced today positive prespecified interim results from the ongoing phase III IMAgINATION study evaluating investigational sefaxersen in adults with primary IgA nephropathy (IgAN). The study met its primary endpoint with sefaxersen achieving statistically significant and clinically meaningful improvements in proteinuria reduction, compared to placebo at 37 weeks, as measured by 24-hour urine protein-to-creatinine ratio (UPCR). Proteinuria is a key indicator of kidney damage and a reduction in UPCR is strongly associated with the preservation of long-term kidney function.^5,6 Sefaxersen is a once-monthly subcutaneous injection designed to enable self-administration for people with IgAN. The safety and tolerability profile of sefaxersen was consistent with previously reported data, with no new safety signals identified.

“These interim phase III results show the clinical potential of sefaxersen to modify a key surrogate endpoint of kidney function in people with IgA nephropathy’’ said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. “Sefaxersen may therefore offer a new treatment option to help slow disease progression and potentially reduce the long-term need for dialysis or kidney transplantation.”

“For patients and families navigating IgAN, the prospect of kidney failure, dialysis, or transplantation creates overwhelming uncertainty,” said Bonnie Schneider, Director and Co-Founder of the IgA Nephropathy Foundation. “As someone who has advocated for this community for over two decades, positive results from the IMAgINATION study give us hope that emerging therapies could help preserve kidney function and transform the treatment landscape.”

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. Interim analysis data will be presented at an upcoming medical congress and shared with health authorities, with the goal of bringing this treatment to patients as soon as possible.

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.^3,4 Typically diagnosed before the age of 40 years, it affects at least 25 adults per million worldwide each year.^7,8 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.⁷

About sefaxersen
Sefaxersen, an investigational highly specific liver-directed antisense oligonucleotide that inhibits factor B production, is the first mRNA-targeted therapy for IgA nephropathy (IgAN).¹ 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.^9,10

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.¹¹ 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.^1,12

Roche licensed sefaxersen from Ionis 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.^11,13 The study enrolled 459 people, who are randomised 1:1 to receive sefaxersen or placebo for 105 weeks.^11,13 Participants may switch to open-label treatment after week 105 at the investigator's discretion or after the common-close timepoint, whichever occurs first.^11,13 The primary endpoint of the study is the change from baseline in the urine protein-to-creatinine ratio at 37 weeks.^11,13

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.^4,7,8 In IgAN, immune complexes deposit in the kidneys, which activates the complement system’s alternative pathway, leading to inflammation and subsequent kidney damage.¹⁴ 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.^3,7 Many current therapies aim to reduce protein levels in the urine and control blood pressure to slow progression of the disease.¹⁵

Updated KDIGO 2025 guidelines* highlight the need to address both the underlying immune-mediated causes of IgAN and the downstream consequences of kidney damage.¹⁶ 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.^15,16

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, autoimmune kidney diseases and severe skin conditions (atopic dermatitis). 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] 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.
[2] Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021;100(4S):S1–S276.
[3] Caster DJ, et al. Clinicopathological characteristics of adult IgA nephropathy in the United States. Kidney Int Rep. 2023;8:1792-1800
[4] Cleveland Clinic. IgA Nephropathy [Internet; cited 2026 Sep 16]. Available from: https://my.clevelandclinic.org/health/diseases/5990-iga-nephropathy
[5] 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.
[6] 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.
[7] Pitcher D, et al. Long-term outcomes in IgA nephropathy. Clin J Am Soc Nephrol. 2023;18:727-738.
[8] 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.
[9] Chiu YL, et al. Alternative complement pathway is activated and associated with galactose-deficient IgA. Front Immunol 2021; 12: 638309.
[10] 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.
[11] 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.
[12] 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.
[13] ClinicalTrials.gov. A Study to Evaluate RO7434656 in Participants With Immunoglobulin A Nephropathy (IgAN) (IMAGINATION) (NCT05797610) [Internet; cited 2026 Sep 16]. Available from: https://clinicaltrials.gov/study/NCT05797610
[14] Wu MY, et al. The emerging role of pathogenesis of IgA nephropathy. J Clin Med. 2018;7:225.
[15] Floege J, et al. Current treatment of IgA nephropathy. Semin Immunopathol. 2021;43:717-728.
[16] 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

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