Positive phase III results for Roche’s Gazyva/Gazyvaro show superiority to standard therapy alone in people with lupus nephritis
Roche announced positive topline results from the phase III REGENCY study of Gazyva®/Gazyvaro® (obinutuzumab) in people with active lupus nephritis. The study met its primary endpoint, showing a higher proportion of patients achieving complete renal response (CRR) at 76 weeks when treated with Gazyva/Gazyvaro plus standard therapy compared to standard therapy alone. Two key secondary endpoints also showed statistically significant and clinically meaningful benefits.
Lupus nephritis affects approximately 1.7 million people worldwide, primarily women of color and childbearing age. Despite current treatments, up to one-third of patients progress to end-stage kidney disease within 10 years. Gazyva/Gazyvaro targets disease-causing B cells, potentially preventing or delaying progression to end-stage kidney disease.
Roche plans to share data with health authorities, including the FDA and EMA, aiming to make this potential new treatment available soon. The drug has already received Breakthrough Therapy Designation from the FDA based on phase II NOBILITY study data.
Roche ha annunciato risultati preliminari positivi dallo studio REGENCY di fase III su Gazyva®/Gazyvaro® (obinutuzumab) in persone con nefrite lupica attiva. Lo studio ha raggiunto il suo obiettivo primario, mostrando una maggiore proporzione di pazienti che hanno ottenuto una risposta renale completa (CRR) dopo 76 settimane di trattamento con Gazyva/Gazyvaro in combinazione con la terapia standard, rispetto alla sola terapia standard. Due importanti endpoint secondari hanno anche mostrato benefici statisticamente significativi e clinicamente rilevanti.
La nefrite lupica colpisce circa 1,7 milioni di persone in tutto il mondo, principalmente donne di colore e in età fertile. Nonostante i trattamenti attuali, fino a un terzo dei pazienti progredisce verso la malattia renale allo stadio terminale entro 10 anni. Gazyva/Gazyvaro agisce contro le cellule B causanti malattie, potenzialmente prevenendo o ritardando la progressione verso la malattia renale allo stadio terminale.
Roche prevede di condividere i dati con le autorità sanitarie, inclusi FDA ed EMA, con l'obiettivo di rendere disponibile presto questo potenziale nuovo trattamento. Il farmaco ha già ricevuto la designazione di terapia innovativa dalla FDA basata sui dati dello studio di fase II NOBILITY.
Roche anunció resultados preliminares positivos del estudio de fase III REGENCY de Gazyva®/Gazyvaro® (obinutuzumab) en personas con lupus nefritis activa. El estudio cumplió su objetivo principal, mostrando una mayor proporción de pacientes que lograron una respuesta renal completa (CRR) a las 76 semanas cuando se trató con Gazyva/Gazyvaro más terapia estándar en comparación con la terapia estándar sola. Dos endpoints secundarios clave también mostraron beneficios estadísticamente significativos y clínicamente relevantes.
La lupus nefritis afecta aproximadamente a 1.7 millones de personas en todo el mundo, principalmente mujeres de color y en edad fértil. A pesar de los tratamientos actuales, hasta un tercio de los pacientes progresa a enfermedad renal en etapa terminal dentro de 10 años. Gazyva/Gazyvaro se dirige a las células B causantes de la enfermedad, potencialmente previniendo o retrasando la progresión hacia la enfermedad renal en etapa terminal.
Roche planea compartir los datos con las autoridades de salud, incluyendo la FDA y la EMA, con el objetivo de hacer disponible pronto este potencial nuevo tratamiento. El medicamento ya ha recibido la designación de terapia innovadora por parte de la FDA basada en los datos del estudio de fase II NOBILITY.
로슈는 긍정적인 초기 결과를 발표했습니다. Gazyva®/Gazyvaro® (오비누투주맙)의 III상 REGENCY 연구는 활동성 루푸스 신염 환자를 대상으로 했습니다. 이 연구는 Gazyva/Gazyvaro와 표준 치료를 병행한 그룹에서 76주 후 완전 신장 반응(CRR)을 달성한 환자의 비율이 표준 치료만 받은 그룹보다 높음을 보여주며, 주요 목표를 달성했습니다. 두 개의 주요 2차 목표도 통계학적으로 유의미하고 임상적으로 의미 있는 이점을 보였습니다.
루푸스 신염은 전 세계에서 약 170만 명에게 영향을 미칩니다, 주로 유색인종 여성과 가임기 여성입니다. 현재 치료에도 불구하고, 환자 3분의 1까지는 10년 이내에 말기 신장 질환으로 진행됩니다. Gazyva/Gazyvaro는 질병을 유발하는 B세포를 표적으로 하여, 말기 신장 질환으로의 진행을 예방하거나 지연시킬 수 있습니다.
로슈는 FDA와 EMA를 포함한 보건 당국과 데이터를 공유할 계획이며, 이 새로운 잠재적 치료제를 곧 이용할 수 있도록 하는 것을 목표로 하고 있습니다. 이 약물은 이미 II상 NOBILITY 연구 데이터를 바탕으로 FDA로부터 혁신 치료제 지정을 받았습니다.
Roche a annoncé des résultats préliminaires positifs de l'étude de phase III REGENCY concernant Gazyva®/Gazyvaro® (obinutuzumab) chez des personnes atteintes d'une lupus néphrite active. L'étude a atteint son objectif principal, montrant une plus grande proportion de patients atteignant une réponse rénale complète (CRR) à 76 semaines lorsqu'ils ont été traités avec Gazyva/Gazyvaro en plus de la thérapie standard par rapport à la thérapie standard seule. Deux objectifs secondaires clés ont également montré des bénéfices statistiquement significatifs et cliniquement pertinents.
La néphrite lupique touche environ 1,7 million de personnes dans le monde, principalement des femmes de couleur et en âge de procréer. Malgré les traitements actuels, jusqu'à un tiers des patients progressent vers une maladie rénale terminale dans les 10 ans. Gazyva/Gazyvaro cible les cellules B responsables de la maladie, ce qui pourrait prévenir ou retarder la progression vers la maladie rénale terminale.
Roche prévoit de partager des données avec les autorités sanitaires, y compris la FDA et l'EMA, dans le but de rendre ce nouveau traitement potentiel disponible prochainement. Le médicament a déjà reçu la désignation de thérapie innovante de la FDA sur la base des données de l'étude de phase II NOBILITY.
Roche hat positive vorläufige Ergebnisse aus der Phase-III-Studie REGENCY zu Gazyva®/Gazyvaro® (Obinutuzumab) bei Menschen mit aktiver Lupusnephritis bekannt gegeben. Die Studie erreichte ihr primäres Endpoint und zeigte einen höheren Anteil an Patienten, die eine vollständige renale Antwort (CRR) nach 76 Wochen erzielten, wenn sie mit Gazyva/Gazyvaro zusammen mit der Standardtherapie behandelt wurden, im Vergleich zur alleinigen Standardtherapie. Zwei wichtige sekundäre Endpunkte zeigten ebenfalls statistisch signifikante und klinisch relevante Vorteile.
Lupusnephritis betrifft etwa 1,7 Millionen Menschen weltweit, hauptsächlich Frauen mit Migrationshintergrund und im gebärfähigen Alter. Trotz der derzeitigen Behandlungen schreitet bis zu ein Drittel der Patienten innerhalb von 10 Jahren zu einer terminalen Nierenerkrankung voran. Gazyva/Gazyvaro zielt auf die krankheitsverursachenden B-Zellen ab, um möglicherweise der Progression zur terminalen Nierenerkrankung vorzubeugen oder diese zu verzögern.
Roche plant, Daten mit Gesundheitsbehörden, darunter die FDA und EMA, zu teilen, mit dem Ziel, diese potenzielle neue Behandlung bald verfügbar zu machen. Das Medikament hat bereits die Breakthrough-Therapie-Bezeichnung von der FDA auf Grundlage der Daten der Phase-II-Studie NOBILITY erhalten.
- Phase III REGENCY study met its primary endpoint, showing superiority of Gazyva/Gazyvaro plus standard therapy over standard therapy alone
- Higher proportion of patients achieved complete renal response (CRR) at 76 weeks with Gazyva/Gazyvaro treatment
- Two key secondary endpoints showed statistically significant and clinically meaningful benefits
- Safety profile was in line with the well-characterized profile of Gazyva/Gazyvaro, with no new safety signals identified
- Gazyva/Gazyvaro received Breakthrough Therapy Designation from the FDA in 2019
- Some secondary endpoints were not statistically significant
Positive phase III results for Roche’s Gazyva/Gazyvaro show superiority to standard therapy alone in people with lupus nephritis
- The REGENCY study met its primary endpoint, demonstrating statistically significant and clinically meaningful treatment benefits in people with active lupus nephritis
- Gazyva/Gazyvaro is designed to target an underlying cause of lupus nephritis, aiming to prevent or delay progression to end-stage kidney disease1,2
- Lupus nephritis is a potentially life-threatening manifestation of an autoimmune disease affecting 1.7 million people worldwide, primarily women; up to one-third
of people on current treatments will progress to end-stage kidney disease within 10 years3-6
Basel, 26 September 2024 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today positive topline results from the phase III REGENCY study of Gazyva®/Gazyvaro® (obinutuzumab) in people with active lupus nephritis. In the study, a higher proportion of people treated with Gazyva/Gazyvaro plus standard therapy (mycophenolate mofetil and glucocorticoids) achieved a complete renal response (CRR) at 76 weeks compared to those treated with standard therapy alone. Safety was in line with the well-characterised profile of Gazyva/Gazyvaro. No new safety signals were identified.
“Gazyva/Gazyvaro achieved a robust complete renal response rate in lupus nephritis, which is associated with long-term preservation of kidney function and delay or prevention of end-stage kidney disease,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “Since dialysis or transplants are often required for patients with advanced kidney disease, these findings could represent an important step forward for people living with this devastating disease.”
“I am very excited about today’s announcement that the phase III REGENCY study has met its primary endpoint,” said Dr. Brad H. Rovin, Director of Nephrology and Medical Director of the Center for Clinical Research Management at The Ohio State University Wexner Medical Center, and investigator for the REGENCY study. “The results of REGENCY are compelling. Obinutuzumab could offer the lupus community an effective new treatment option for controlling this difficult disease that can be associated with high morbidity for individuals living with lupus.”
Two key secondary endpoints showed statistically significant and clinically meaningful benefits with Gazyva/Gazyvaro - the endpoint proportion of patients achieving CRR with a successful reduction of corticosteroid use, and an improvement in proteinuric response (both at 76 weeks). These endpoints are important indicators for achieving better disease control in lupus nephritis. Other secondary endpoints were not statistically significant, but numerically greater responses were observed for Gazyva/Gazyvaro in several endpoints. *
Data are being shared with health authorities, including the US Food and Drug Administration (FDA) and the European Medicines Agency, with the goal of making this potential new treatment option for lupus nephritis available as soon as possible. Data are also being submitted for publication in a medical journal and presentation at a future medical congress.
Lupus nephritis is a potentially life-threatening manifestation of an autoimmune disease that affects approximately 1.7 million people worldwide, predominantly women and mostly of colour and childbearing age.3-5, 7 In lupus nephritis, disease-causing B cells drive persistent inflammation that damages the kidneys.2 Despite current treatment options, up to a third of people will develop end-stage kidney disease within 10 years, where dialysis or transplant are the only available options and the risk of mortality is high.6 Data suggest that Gazyva/Gazyvaro depletes disease-causing B cells, helping to limit further damage to the kidneys and potentially preventing or delaying progression to end-stage kidney disease.8
Gazyva/Gazyvaro® was granted Breakthrough Therapy Designation by the US FDA in 2019, based on data from the phase II NOBILITY study.9 Breakthrough Therapy Designation is designed to accelerate the development and regulatory review of medicines intended to treat serious or life-threatening conditions where preliminary clinical evidence has indicated they may demonstrate substantial improvement over existing therapies.
In addition to REGENCY, Gazyva/Gazyvaro is being investigated in children and adolescents with lupus nephritis, people with membranous nephropathy, childhood-onset idiopathic nephrotic syndrome and systemic lupus erythematosus (SLE), an autoimmune disease that commonly affects the kidneys and can lead to lupus nephritis.10-13 Our pipeline also includes RG6299 (ASO factor B), an antisense oligonucleotide therapy being investigated in people with primary immunoglobulin A nephropathy at high risk of progression, Lunsumio® (mosunetuzumab), a first-in-class CD20xCD3 T-cell engaging bispecific antibody being investigated in SLE, PiaSky® (crovalimab), a novel recycling monoclonal antibody being investigated in atypical haemolytic uraemic syndrome and RG6382, a CD19xCD3
T-cell engaging bispecific antibody being investigated in SLE.14-18
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.
For more information, please visit www.roche.com.
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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
[1] Herter S, et al. Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab in vitro and in xenograft models. Mol Cancer Ther. 2013;12(10):2031-42
[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
[11] Clinicaltrials.gov. Obinutuzumab in Primary MN (ORION) [Internet; cited September 2024]. Available from: https://clinicaltrials.gov/study/NCT05050214
[12] Clinical trials.gov. A Study to Evaluate the Efficacy and Safety of Obinutuzumab Versus MMF in Participants With Childhood Onset Idiopathic Nephrotic Syndrome (INShore) [Internet; cited September 2024]. Available from: https://clinicaltrials.gov/study/NCT05627557
[13] Clinicaltrials.gov. A Study to Evaluate the Efficacy and Safety of Obinutuzumab in Participants With Systemic Lupus Erythematosus (ALLEGORY) [Internet; cited September 2024]. Available from: https://clinicaltrials.gov/study/NCT04963296
[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
[17] Clinicaltrials.gov. A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Pediatric Participants With Atypical Hemolytic Uremic Syndrome (aHUS) (COMMUTE-p) [internet; cited September 2024]. Available from: https://clinicaltrials.gov/study/NCT04958265
[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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