Genentech Presents Interim Phase III Data Showing Sefaxersen Significantly Reduced Proteinuria in People With IgA Nephropathy (IgAN)

- 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 subgroups -

- 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 inflammation -

- Investigational sefaxersen is intended to be a once-monthly subcutaneous injection and designed to enable convenient self-administration at home -

- 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 -

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Genentech, a member of the Roche Group (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 optimized 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). Proteinuria is a key indicator of kidney damage and a reduction in UPCR is strongly associated with the preservation of long-term kidney function. Results presented at the American Society of Nephrology (ASN) Kidney Week 2026 also showed that, among patients with baseline hematuria (blood in urine), a greater proportion of patients achieved hematuria resolution at Week 37 with sefaxersen versus placebo.

“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, M.D., Ph.D., 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. Sefaxersen was well tolerated with a safety profile consistent with the previously reported Phase II study, exhibiting no new safety signals.

Sefaxersen is an investigational once-monthly subcutaneous injection designed to enable convenient self-administration for people with IgAN. 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. 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. 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.

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). 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.

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. 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.

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

About the IMAgINATION Study

IMAgINATION [NCT05797610] is a Phase III, multicenter, randomized, 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. The study enrolled 459 people, who are randomized 1:1 to receive sefaxersen or placebo for 105 weeks. Participants may switch to open-label treatment after week 105 at the investigator’s discretion or after the common-close timepoint, whichever occurs first. The primary endpoint of the study is the change from baseline in the urine protein-to-creatinine ratio at 37 weeks.

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

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

About Genentech in Immunology

Genentech is committed to harnessing pioneering science and innovation to address critical unmet needs for patients with immune-mediated diseases. Our pipeline includes over a dozen clinical programs in immunology aiming to transform care for people living with lupus, MASH, ulcerative colitis, Crohn’s disease, immunoglobulin A nephropathy, idiopathic nephrotic syndrome, and rheumatoid arthritis. We are investing end-to-end in immunology from discovery to R&D to commercialization across a variety of modalities including monoclonal antibodies, bispecifics, and CAR-T cell therapies to help solve some of the most difficult challenges in immunology today.

About Genentech

Founded 50 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

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