Positive Interim Data Shows Genentech’s Sefaxersen Significantly Reduces Proteinuria in People With IgA Nephropathy (IgAN)

Genentech, a member of the Roche Group (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. 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, M.D., Ph.D., 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.”

“Despite recent advances, important unmet needs remain, including targeted approaches that address distinct pathways of disease progression,” said Bonnie Schneider, director and co-founder of the IgA Nephropathy Foundation. “Positive results from the IMAgINATION study represent the potential of targeted treatments that are effective and convenient, and will hopefully help delay or avoid long-term complications of 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. 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. Typically diagnosed before the age of 40 years, it affects at least 25 adults per million worldwide each year. 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

Sefaxersen, an investigational highly specific liver-directed antisense oligonucleotide that inhibits factor B production, is the first mRNA-targeted therapy for 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 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, atopic dermatitis, 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.

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