Roche’s Gazyva Shows Breakthrough Results in Treating Lupus Nephritis, Offering Hope for Kidney Disease Patients

Roche’s Gazyva Shows Breakthrough Results in Treating Lupus Nephritis, Offering Hope for Kidney Disease Patients

(IN BRIEF) Roche has announced positive results from its phase III REGENCY study, showing that its drug Gazyva®/Gazyvaro® (obinutuzumab) significantly outperformed standard therapy in treating active lupus nephritis. The study found that patients receiving Gazyva/Gazyvaro, in combination with standard therapies, achieved higher rates of complete renal response (CRR) and showed promising long-term kidney protection, potentially delaying progression to end-stage kidney disease. The results are being shared with health authorities, and Roche aims to bring this new treatment option to market quickly. Lupus nephritis, which affects 1.7 million people globally, is a life-threatening condition that can lead to kidney failure if untreated.

(PRESS RELEASE) BASEL, 26-Sep-2024— /EuropaWire/ — Roche announced promising results from its phase III REGENCY study on September 26, 2024, demonstrating the superior efficacy of Gazyva®/Gazyvaro® (obinutuzumab) in treating patients with active lupus nephritis. The study revealed that individuals receiving Gazyva/Gazyvaro in combination with standard therapy (mycophenolate mofetil and glucocorticoids) achieved a significantly higher complete renal response (CRR) rate at 76 weeks compared to those on standard therapy alone. Additionally, safety outcomes were consistent with the known profile of Gazyva/Gazyvaro, and no new safety concerns emerged.

Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development, highlighted the significance of the CRR results, which offer hope for long-term kidney preservation and a potential delay in progression to end-stage kidney disease. Lupus nephritis affects 1.7 million people globally, and advanced kidney disease often necessitates dialysis or transplant. “These findings could represent an important step forward for people living with this devastating disease,” Garraway said.

Dr. Brad H. Rovin from The Ohio State University Wexner Medical Center, an investigator for the study, described the results as “compelling,” emphasizing the potential of obinutuzumab to become an effective new option for managing lupus nephritis.

Key secondary endpoints further supported Gazyva/Gazyvaro’s benefits, showing statistically significant improvements in proteinuria and CRR with a reduction in corticosteroid use. While other secondary endpoints were not statistically significant, numerically superior outcomes were observed with Gazyva/Gazyvaro.

Roche is working closely with health authorities, including the U.S. FDA and European Medicines Agency, to expedite regulatory approval and make this new treatment option available to patients as soon as possible.

Lupus nephritis, primarily affecting women, particularly those of color and childbearing age, is a life-threatening autoimmune condition. B cells drive persistent inflammation in the kidneys, often leading to end-stage kidney disease, where dialysis or transplant becomes necessary. Gazyva/Gazyvaro is designed to deplete these disease-causing B cells, potentially delaying the progression of the disease.

This breakthrough treatment had received FDA Breakthrough Therapy Designation in 2019 based on previous positive data from the NOBILITY study. Roche continues to explore the use of Gazyva/Gazyvaro in pediatric lupus nephritis, membranous nephropathy, and other autoimmune diseases.

Through ongoing trials, Roche remains committed to developing innovative treatments to help people living with lupus nephritis and other serious kidney conditions.

About Gazyva/Gazyvaro in kidney diseases
Gazyva®/Gazyvaro® (obinutuzumab) is a Type II engineered humanised monoclonal antibody designed to attach to CD20, a protein found on certain types of B cells.1 In lupus nephritis, disease-causing B cells drive persistent inflammation that damages the kidneys.2 We can target an underlying cause of lupus nephritis to help gain better control of the disease by depleting disease-causing B cells with Gazyva/Gazyvaro, aiming to protect the kidneys from further damage and potentially prevent or delay progression to end-stage kidney disease.1,2,8 Gazyva/Gazyvaro is already approved in 100 countries for various types of lymphoma. In the United States, Gazyva/Gazyvaro is part of a collaboration between Genentech and Biogen.

About the REGENCY study
REGENCY [NCT04221477] is a phase III, randomised, double-blind, placebo-controlled, multicentre study investigating the efficacy and safety of Gazyva®/Gazyvaro® (obinutuzumab) plus standard therapy (mycophenolate mofetil and glucocorticoids) in people 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 people, who were randomised 1:1 to receive either biannual intravenous dosing of Gazyva/Gazyvaro plus standard therapy or placebo plus standard therapy. REGENCY was designed based on robust phase II data and conducted during the COVID-19 pandemic. The study population was representative of the real-world population of people with lupus nephritis. The primary endpoint was the proportion of people who achieved complete renal response (CRR) at 76 weeks. Key secondary endpoints included the proportion of people who achieved CRR at week 76 with successful reduction of corticosteroid use (prednisone taper); the proportion who achieved proteinuric response at 76 weeks; mean change in estimated glomerular filtration rate at 76 weeks; death or renal related events through week 76 and overall renal response at 50 weeks. Safety and tolerability were also assessed.

About lupus nephritis
Lupus nephritis is a potentially life-threatening manifestation of systemic lupus erythematosus, an autoimmune disease that commonly affects the kidneys.3 Lupus nephritis affects approximately 1.7 million people worldwide.4,5 Lupus nephritis has a profound impact on the lives and outlook of those affected and even with the latest treatments, the damage caused to the kidneys usually gets worse over time, with up to a third of people progressing to end-stage kidney disease within 10 years, where the only options are dialysis or transplant.6 Lupus nephritis predominantly affects women, mostly women of colour and usually of childbearing age.7 Currently, there is no cure.3

About Roche in kidney diseases
For 20 years, we have combined innovation, scientific expertise and commitment to patients to address unmet needs in kidney diseases. Our industry-leading pipeline includes several ongoing phase I-III clinical studies of immune-mediated investigational therapies with the aim of bringing innovative new treatment options to people living with kidney and kidney-related diseases, including lupus nephritis, membranous nephropathy, immunoglobulin A nephropathy, atypical haemolytic uraemic syndrome, childhood-onset idiopathic nephrotic syndrome and systemic lupus erythematosus, an autoimmune disease that can lead to lupus nephritis.

About Roche
Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice.

For over 125 years, sustainability has been an integral part of Roche’s business. As a science-driven company, our greatest contribution to society is developing innovative medicines and diagnostics that help people live healthier lives. Roche is committed to the Science Based Targets initiative and the Sustainable Markets Initiative to achieve net zero by 2045. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan.

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*Mean change in estimated glomerular filtration rate at 76 weeks, death or renal-related events through week 76, and overall renal response at 50 weeks.

References
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[2] Atisha-Fregoso Y, et al. Meant to B: B cells as a therapeutic target in systemic lupus erythematosus. J Clin Invest. 2021;131(12):e149095
[3] Hocaoglu et al. Incidence, Prevalence, and Mortality of Lupus Nephritis: A Population-Based Study Over Four Decades—The Lupus Midwest Network (LUMEN). Arthritis Rheumatol. 202;75(4):567–73
[4] Tian J, et al. Global epidemiology of systemic lupus erythematosus: a comprehensive systematic analysis and modelling study. Ann Rheum Dis. 2023;82:351-56
[5] Hoi A, et al. Systemic lupus erythematosus. The Lancet. 2024;403(10441):2326-38
[6] Mok C, et al. Treatment of lupus nephritis: consensus evidence and perspectives. Nat Rev Rheumatol. 2023;19:227-38
[7] Anders HJ, Saxena R, Zhao MH, Parodis I, Salmon JE, Mohan C. Lupus nephritis. Nat Rev Dis Primers. 2020;6(1):7. doi: 10.1038/s41572-019-0141-9
[8] Furie RA, et al. B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2022;81(1):100-7
[9] Roche. FDA grants Breakthrough Therapy Designation for Roche’s Gazyva (obinutuzumab) in Lupus Nephritis. 2019 [Internet, cited September 2024]. Available from: https://www.roche.com/investors/updates/inv-update-2019-09-18
[10] Clinicaltrials.gov. A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Obinutuzumab in Adolescents With Active Class III or IV Lupus Nephritis and the Safety and PK of Obinutuzumab in Pediatric Participants (POSTERITY) [Internet; cited September 2024]. Available from: https://clinicaltrials.gov/study/NCT05039619
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[14] Clinicaltrials.gov. A Study to Evaluate the Efficacy and Safety of RO7434656 in Participants With Primary Immunoglobulin A (IgA) Nephropathy at High Risk of Progression (IMAGINATION) [Internet; cited September 2024]. Available from: https://clinicaltrials.gov/study/NCT05797610
[15] Clinicaltrials.gov. A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered Mosunetuzumab to Participants With Systemic Lupus Erythematosus [Internet; cited September 2024]. Available from: https://clinicaltrials.gov/study/NCT05155345
[16] Clinicaltrials.gov. A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS) (COMMUTE-a) [Internet; cited September 2024]. Available from: https://clinicaltrials.gov/study/NCT04861259
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[18] Clinicaltrials.gov. Clinical Study of A-319 in the Treatment of Active/​Refractory Systemic Lupus Erythematosus [internet; cited September 2024]. Available from: https://clinicaltrials.gov/study/NCT06400537

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SOURCE: Roche