Mycophenolate Mofetil

Genentech plans to expand the label for its CD20-targeting antibody Gazyva following positive late-stage data in an autoimmune disease that impacts the kidneys. In the Phase 3 REGENCY study , a higher proportion of patients with lupus nephritis treated with Gazyva and standard therapy achieved a complete renal response at 76 weeks compared to those treated with just standard therapy. The standard therapies used in the trial were the immunosuppressant mycophenolate mofetil and the corticosteroid called glucocorticoid. The company said that the data are being shared with the FDA and other health regulatory agencies, with a goal to make Gazyva available “as soon as possible.” According to Genentech, lupus nephritis is a manifestation of systemic lupus erythematosus, an autoimmune disease. Lupus nephritis impacts about 1.7 million people worldwide and gets worse over time, with up to a third of people progressing to end-stage kidney disease within a decade. The drug scored breakthrough designation from the FDA in 2019 in the indication. Genentech CMO and head of global product development Levi Garraway said in a statement that the drug achieved a “robust” complete renal response. “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,” Garraway added. The trial also showed statistically significant and clinically meaningful results in secondary endpoints at 76 weeks, including the proportion of patients achieving complete renal response with a successful reduction of corticosteroid use, and an improvement in proteinuric response. However, other secondary endpoints weren’t “statistically significant, but numerically greater responses were observed for Gazyva in several endpoints,” the company said. Gazyva, which is already approved to treat types of lymphoma, is being investigated in other areas, including in children and adolescents with lupus nephritis, people with membranous nephropathy, childhood-onset idiopathic nephrotic syndrome and systemic lupus erythematosus. In Roche’s half-year report, Gazyva pulled in about $523.7 million (445 million CHF), a 15% increase from the same time last year.

– The REGENCY study met its primary endpoint, demonstrating statistically significant and clinically meaningful treatment benefits in people with active lupus nephritis – – Gazyva is designed to target an underlying cause of lupus nephritis, aiming to prevent or delay progression to end-stage kidney disease – – 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 years – SOUTH SAN FRANCISCO, CA, USA I September 26, 2024 I Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today positive topline results from the Phase III REGENCY study of Gazyva® (obinutuzumab) in people with active lupus nephritis. In the study, a higher proportion of people treated with Gazyva 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-characterized profile of Gazyva. No new safety signals were identified. “Gazyva 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., 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 – 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 in several endpoints.* Data are being shared with health authorities, including the U.S. 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 women of color and childbearing age. In lupus nephritis, disease-causing B cells drive persistent inflammation that damages the kidneys. 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. Data suggest that Gazyva depletes disease-causing B cells, helping to limit further damage to the kidneys and potentially preventing or delaying progression to end-stage kidney disease. Gazyva was granted Breakthrough Therapy Designation by the FDA in 2019, based on data from the Phase II NOBILITY study. 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 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. 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 hemolytic uremic syndrome and RG6382, a CD19xCD3 T-cell engaging bispecific antibody being investigated in SLE. *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. About Gazyva in Kidney Diseases Gazyva® (obinutuzumab) is a Type II engineered humanized monoclonal antibody designed to attach to CD20, a protein found on certain types of B cells. In lupus nephritis, disease-causing B cells drive persistent inflammation that damages the kidneys. 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, aiming to protect the kidneys from further damage and potentially prevent or delay progression to end-stage kidney disease. Gazyva is already approved in 100 countries for various types of lymphoma. In the United States, Gazyva is part of a collaboration between Genentech and Biogen. About the REGENCY Study REGENCY [ NCT04221477 ] is a Phase III, randomized, double-blind, placebo-controlled, multicenter study investigating the efficacy and safety of Gazyva® (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 randomized 1:1 to receive either biannual intravenous dosing of Gazyva 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. Lupus nephritis affects approximately 1.7 million people worldwide. 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. Lupus nephritis predominantly affects women, mostly women of color and usually of childbearing age. Currently, there is no cure. Gazyva U.S. Indications Gazyva® (obinutuzumab) is a prescription medicine used: Please visit http://www.Gazyva.com for the Gazyva full Prescribing Information, including BOXED WARNINGS, for additional Important Safety Information. About Lunsumio ® (mosunetuzumab-axgb) Lunsumio® is a first-in-class CD20xCD3 T-cell engaging bispecific antibody designed to target CD20 on the surface of B cells and CD3 on the surface of T cells. This dual targeting activates and redirects a patient’s existing T cells to engage and eliminate target B cells by releasing cytotoxic proteins into the B cells. A robust clinical development program for Lunsumio is ongoing, investigating the molecule as a monotherapy and in combination with other medicines, for the treatment of people with B-cell non-Hodgkin’s lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma, and other blood cancers. Lunsumio U.S. Indication Lunsumio® (mosunetuzumab-axgb) is a prescription medicine used to treat adults with follicular lymphoma whose cancer has come back or did not respond to previous treatment, and who have already received two or more treatments for their cancer. It is not known if Lunsumio is safe and effective in children. The conditional approval of Lunsumio is based on response rate. There are ongoing studies to establish how well the drug works. Please see Important Safety Information, including Serious Side Effects, as well as the Lunsumio full Prescribing Information and Medication Guide or visit https://www.Lunsumio.com . PiaSky U.S. Indication PiaSky® is a prescription medicine used to treat a disease called paroxysmal nocturnal hemoglobinuria (PNH) in adults and children 13 years of age or older who weigh at least 88 pounds (40 kg). It is not known if PiaSky is safe and effective in children under 13 years of age and in people who weigh less than 88 pounds (40kg). Please see the full Prescribing Information and Medication Guide for additional Important Safety Information, including Serious Side Effects , or visit https://www.piasky.com . About Genentech 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 hemolytic uremic syndrome, childhood-onset idiopathic nephrotic syndrome and systemic lupus erythematosus, an autoimmune disease that can lead to lupus nephritis. About Genentech Founded more than 40 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 . SOURCE: Genentech