FDA Accepts sBLA for Genentech’s Gazyva in Lupus Nephritis
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), has announced that the U.S. Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application (sBLA) for Gazyva® (obinutuzumab) for the treatment of lupus nephritis. This filing acceptance is based on promising results from the Phase III REGENCY study, which demonstrated that Gazyva, when combined with standard therapy, significantly improved complete renal response (CRR) compared to standard therapy alone. The FDA is anticipated to make a decision on the approval by October 2025.
Lupus nephritis is a severe and potentially life-threatening complication of systemic lupus erythematosus (SLE) that affects kidney function. If left untreated, it can lead to kidney failure, requiring dialysis or transplantation. Given the critical need for effective treatments, the FDA’s acceptance of this sBLA underscores the urgency of providing better therapeutic options for patients affected by this debilitating condition.
“In people with lupus nephritis, Gazyva demonstrated a complete renal response benefit, a meaningful clinical outcome linked to preservation of kidney function, and slowing or prevention of end-stage kidney disease,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development at Genentech. “The FDA’s sBLA acceptance for Gazyva recognizes the need to provide a more effective treatment option for people living with this devastating disease.”
Louise Vetter, President and Chief Executive Officer of the Lupus Foundation of America, also emphasized the importance of advancing treatment options. “Lupus nephritis is a debilitating and potentially life-threatening condition that can lead to kidney failure and require dialysis or transplantation. Given the relatively young age of onset, people with lupus nephritis experience more years of disease-related complications and decreased quality of life due to the significant burden of this illness. We are hopeful for a new treatment option that can effectively reduce these risks and improve the health of all people affected by this disease.”
Phase III REGENCY Study Results
The Phase III REGENCY study, which was presented at the World Congress of Nephrology (WCN) and published in the New England Journal of Medicine in February 2025, revealed that nearly half of the patients who received Gazyva plus standard therapy achieved CRR. This was a statistically significant and clinically meaningful improvement compared to those who received standard therapy alone. The study also showed improvements in key biomarkers, including complement levels and reductions in anti-dsDNA, which are associated with disease activity and inflammation.
Additionally, a pre-specified subgroup analysis indicated that the CRR benefit was consistent across different patient subgroups, reinforcing Gazyva’s potential to address a broad patient population with high unmet medical needs. Importantly, the safety profile of Gazyva in the REGENCY study was consistent with previous observations from its hematology-oncology indications.
Data from the REGENCY study will also support a filing submission with the European Medicines Agency (EMA), expanding the potential for Gazyva’s approval in international markets.
Gazyva as a Potential Breakthrough Therapy
Gazyva is the only anti-CD20 monoclonal antibody in a randomized Phase III study to demonstrate a CRR benefit in lupus nephritis. The FDA previously granted Gazyva Breakthrough Therapy Designation in 2019 based on findings from the Phase II NOBILITY study.
Beyond lupus nephritis, Gazyva is also being explored for potential applications in pediatric and adolescent populations, as well as in other kidney-related conditions, including membranous nephropathy and childhood-onset idiopathic nephrotic syndrome. Additionally, Gazyva is being investigated for systemic lupus erythematosus (SLE), an autoimmune disease that commonly affects the kidneys and can lead to lupus nephritis.
Expanding Genentech’s Immunological Kidney Disease Pipeline
Genentech continues to expand its pipeline of investigational treatments for immunological kidney diseases. The company is also developing Sefaxersen (ASO factor B), an antisense oligonucleotide therapy being studied in patients with primary immunoglobulin A nephropathy at high risk of progression. Additionally, the company is evaluating:
- Lunsumio® (mosunetuzumab): A first-in-class CD20xCD3 T-cell engaging bispecific antibody being investigated for systemic lupus erythematosus (SLE).
- PiaSky® (crovalimab): A novel recycling monoclonal antibody under investigation for atypical hemolytic uremic syndrome.
- RG6382: A CD19xCD3 T-cell engaging bispecific antibody being studied for SLE.
- P-CD19CD20-ALLO1: An allogeneic dual CAR-T therapy being explored as a potential treatment for autoimmune conditions.
About Gazyva in Kidney Diseases
Gazyva (obinutuzumab) is a Type II engineered humanized monoclonal antibody designed to attach to CD20, a protein found on B cells. In lupus nephritis, disease-causing B cells drive persistent inflammation that damages the kidneys. By targeting and depleting these B cells, Gazyva aims to mitigate kidney damage and slow disease progression, potentially delaying or preventing end-stage kidney disease.
Gazyva is already approved in over 100 countries for various types of lymphoma. In the United States, it is marketed through a collaboration between Genentech and Biogen.
About the REGENCY Study
The Phase III REGENCY trial [NCT04221477] was a randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy and safety of Gazyva plus standard therapy (mycophenolate mofetil and glucocorticoids) in individuals with active/chronic International Society of Nephrology/Renal Pathology Society 2003 proliferative Class III or IV lupus nephritis, with or without Class V.
The study enrolled 271 participants, who were randomly assigned to receive either biannual intravenous doses of Gazyva plus standard therapy or a placebo plus standard therapy. Key secondary endpoints included the proportion of patients achieving CRR with reduced corticosteroid use, proteinuric response at 76 weeks, changes in estimated glomerular filtration rate, and renal-related events through week 76. Safety and tolerability assessments were also conducted.
About Lupus Nephritis
Lupus nephritis is a severe manifestation of systemic lupus erythematosus (SLE), affecting approximately 1.7 million people worldwide. This condition disproportionately impacts women, particularly women of color, and typically manifests in early adulthood. Despite advancements in treatment, many individuals progress to end-stage kidney disease within 10 years, necessitating dialysis or transplantation. There remains a significant unmet need for therapies that can slow disease progression and improve long-term outcomes for affected individuals.
Gazyva U.S. Indications and Safety Information
Gazyva is currently approved for use in treating:
- Chronic lymphocytic leukemia (CLL) in combination with chlorambucil for previously untreated patients.
- Follicular lymphoma (FL) in combination with bendamustine for patients who did not respond to prior rituximab-containing regimens.
- Stage II bulky, III, or IV follicular lymphoma in combination with chemotherapy for treatment-naïve patients.
Important Safety Information
Patients should discuss potential side effects with their healthcare providers. Gazyva can cause serious adverse effects, including:
- Hepatitis B Reactivation: Patients should be screened before starting therapy, as Gazyva may reactivate hepatitis B virus, potentially leading to severe liver complications.
- Progressive Multifocal Leukoencephalopathy (PML): A rare but serious brain infection that can be fatal.
Patients who have had allergic reactions to Gazyva should not receive the medication.
As the FDA reviews the sBLA for Gazyva in lupus nephritis, the medical community remains hopeful that this treatment will offer a new, effective option for patients in need.
