Phase III ALLEGORY trial achieved its primary and all key secondary endpoints with Gazyva, an anti-CD20 monoclonal antibody engineered to enhance B cell depletion.
– Gazyva shows potential to become a transformative new standard of care for up to 3.4 million people living with systemic lupus erythematosus (SLE) worldwide.
– Upon approval, Gazyva would be the first anti-CD20 therapy for SLE designed to directly target B cells, a central driver of inflammation and disease activity.
– These positive results build on recent milestones, including U.S. FDA approval and a favorable EU CHMP opinion for Gazyva in lupus nephritis, as well as encouraging Phase III outcomes from the INShore study in idiopathic nephrotic syndrome.
Genentech’s Gazyva Demonstrates Significant Clinical Benefit in Phase III ALLEGORY Study for Systemic Lupus Erythematosus
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced positive results from the Phase III ALLEGORY study evaluating Gazyva® (obinutuzumab) in adults with systemic lupus erythematosus (SLE) receiving standard therapy. The study achieved its primary endpoint, showing that a significantly higher percentage of patients treated with Gazyva achieved at least a four-point improvement in the SLE Responder Index 4 (SRI-4) at 52 weeks, compared to those on standard therapy alone.
SRI-4 is a recognized composite measure that evaluates changes in disease activity, symptoms, and overall physical health to determine treatment efficacy in SLE. In addition to the primary endpoint, all key secondary endpoints were met, underscoring the broad clinical benefit of Gazyva in managing SLE. Importantly, no new safety signals were observed, and the overall safety profile was consistent with the well-established tolerability of Gazyva.
“Systemic lupus erythematosus is a lifelong and unpredictable disease that can lead to irreversible organ damage and severe, life-threatening complications,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development at Genentech. “These pivotal findings are unprecedented — they show that Gazyva can effectively control disease activity and may delay or prevent long-term organ damage in people with SLE. We are eager to share these data with health authorities worldwide to make this potential new standard of care available as soon as possible.”
Robust Secondary Endpoint Outcomes
Results from ALLEGORY demonstrated statistically significant and clinically meaningful improvements across all key secondary endpoints when compared with standard therapy. These included:
- BICLA (British Isles Lupus Assessment Group-based Composite Lupus Assessment) response at week 52
- Sustained corticosteroid control from weeks 40 to 52
- Sustained SRI-4 response from weeks 40 to 52
- A six-point improvement in SRI-6 at week 52
- Longer time to first disease flare over 52 weeks, as defined by the BILAG index
Collectively, these findings indicate that Gazyva provides comprehensive disease control and could meaningfully reduce flare frequency and severity.
Addressing a Major Unmet Need in Lupus Care
Systemic lupus erythematosus affects more than three million people worldwide, primarily women aged 15–45, with women of color disproportionately affected. The disease causes inflammation and damage to multiple organs, often leading to chronic complications. Within five years of diagnosis, about half of SLE patients develop lupus nephritis, a severe kidney condition that can be life-threatening.
By improving disease control, Gazyva may help limit flares, preserve organ function, and reduce the risk of progression to lupus nephritis, addressing critical unmet needs in lupus management.
A Potential First-in-Class Anti-CD20 Therapy for SLE
The ALLEGORY study results will be presented at an upcoming major medical conference and submitted to global health authorities, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
If approved, Gazyva would become the first anti-CD20 therapy for SLE designed to directly target and deplete B cells, a key driver of autoimmune activity in lupus.
Expanding Evidence in Immune-Mediated Diseases
ALLEGORY marks the third successful Phase III trial for Gazyva in immune-mediated conditions, following positive results from the REGENCY study in lupus nephritis and the INShore study in idiopathic nephrotic syndrome.
Together, these results reinforce Gazyva’s potential as a transformative therapy across a spectrum of autoimmune and immune-related diseases. The therapy is engineered to eliminate targeted B cells both directly and in coordination with the body’s immune defenses — offering a precise approach to controlling disease activity.
Continuing the Commitment to Rheumatology and Nephrology Innovation
Genentech is further evaluating Gazyva in children and adolescents with lupus nephritis, as well as adults with membranous nephropathy, as part of its commitment to advancing treatments for immune-mediated rheumatology and nephrology disorders.
With the promising results from ALLEGORY, Genentech continues to build on its legacy of innovation in autoimmune disease research — aiming to redefine the standard of care for millions living with lupus and related conditions worldwide.
About Gazyva
Gazyva® (obinutuzumab) is a humanized monoclonal antibody designed with a Type II anti-CD20 region, for direct B cell death and a glycoengineered Fc region, for higher binding affinity and increased antibody-dependent cellular cytotoxicity (ADCC). CD20 is a protein found on certain types of B cells. Gazyva is approved for adults with lupus nephritis in the U.S. who are receiving standard therapy. In October 2025, the European Medicines Agency’s Committee for Medicinal Products for Human Use recommended approval in the European Union, with a final decision expected from the European Commission in the near future. Gazyva is also approved in 100 countries for various types of hematological cancers.
About the ALLEGORY Study
ALLEGORY [NCT04963296] is a Phase III, randomized, double-blind, placebo-controlled, multicenter study, investigating the efficacy and safety of Gazyva® (obinutuzumab) compared with standard therapy in adults with systemic lupus erythematosus (SLE) on standard therapy. The study enrolled approximately 300 people, who were randomized 1:1 to receive Gazyva or placebo for up to one year (52 weeks), followed by an open-label period with Gazyva for up to 104 weeks. The primary endpoint is the percentage of people who achieve SLE Responder Index four at week 52.
About Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is a potentially life-threatening autoimmune disease that affects more than three million people worldwide, and rising. Due to the non-specific symptoms, it can take two to six years for an accurate diagnosis. During this time, disease severity and organ damage, due to repeated flares of disease activity, typically worsens and quality of life declines.
Around half of people with SLE will develop lupus nephritis within five years of a lupus diagnosis. In lupus nephritis, the disease activity primarily affects the kidneys and there is a risk of end-stage kidney disease, where dialysis and transplant are the only treatment options.
There is a need for additional targeted therapies that can effectively control disease activity and potentially delay or prevent the onset of lupus nephritis.
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