Company Announcements

– Nearly half of patients on Gazyva plus standard therapy achieved a complete renal response (CRR), with a statistically significant and clinically meaningful improvement, compared to standard treatment alone –

– Analysis showed consistent CRR benefit across patient subgroups highlighting potential to treat a broad patient population with high unmet need –

– Gazyva is the only anti-CD20 monoclonal antibody in a phase III study to demonstrate CRR benefit, which is associated with preservation of kidney function and delay or prevention of end-stage kidney disease –

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Feb. 7, 2025-- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that a detailed analysis of its Phase III REGENCY trial of Gazyva^® (obinutuzumab) in people with active lupus nephritis (LN) was published in the New England Journal of Medicine. The trial demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of complete renal response (CRR), showing that 46.4% of people treated with Gazyva plus standard therapy (mycophenolate mofetil and glucocorticoids) achieved CRR at 76 weeks compared with 33.1% of people treated with standard therapy alone (adjusted difference 13.4%, 95% CI, 2.0%-24.8%; p=0.0232). This was accompanied by clinically meaningful improvements in complement levels and reductions in anti-dsDNA, markers of disease activity and inflammation.

Data were presented at the World Congress of Nephrology (WCN) 2025 and are being shared with health authorities, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency.

“The fact that nearly half of lupus nephritis patients achieved a complete renal response, together with clinically meaningful benefits observed consistently across subgroups, indicates superior disease control with Gazyva compared to standard treatment alone,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “Lupus nephritis disproportionately affects younger women, mostly women of color, often leading to end-stage kidney disease. Our goal is to address this urgent need by providing a more effective treatment option.”

“The positive REGENCY study results confirmed the findings of an earlier trial that administration of obinutuzumab, a therapy which targets B cells, benefited patients with lupus nephritis more than standard treatment alone,” said Dr. Richard Furie, the Marilyn and Barry Rubenstein Chair in Rheumatology and Chief of the Division of Rheumatology at Northwell Health. “It is also gratifying to see that patients who received obinutuzumab were not only more likely to achieve the desired outcome but were able to taper corticosteroids at the same time.”

Gazyva’s safety profile was consistent with the well-characterized profile observed in its hematology-oncology indications. Key secondary endpoints showed that at week 76, patients who received Gazyva plus standard therapy were more likely to achieve CRR, with a successful reduction of corticosteroid use than standard therapy alone. In addition, a higher proportion of patients also showed improvement in proteinuric response when treated with Gazyva plus standard therapy versus standard therapy alone. These endpoints are important indicators for achieving better disease control in lupus nephritis. As seen in pre-specified subgroup analyses, a benefit in CRR with Gazyva over standard therapy alone was consistent across all subgroups of patients including indicators of more active lupus nephritis, Class IV lupus nephritis, concomitant Class V disease, higher baseline proteinuria levels, and/or greater serologic activity.

Further results for key secondary endpoints can be found in the table below and additional post hoc analysis is ongoing.

Lupus nephritis is a potentially life-threatening manifestation of an autoimmune disease that affects approximately 1.7 million people worldwide, predominantly women, mostly of color and childbearing age. 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.

Gazyva is the only anti-CD20 monoclonal antibody to demonstrate a CRR benefit in a randomized phase III study in lupus nephritis. Based on data from the Phase II NOBILITY study, Gazyva was granted Breakthrough Therapy Designation by the U.S. FDA in 2019. 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.

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:

• With the chemotherapy drug, chlorambucil, to treat chronic lymphocytic leukemia (CLL) in adults who have not had previous CLL treatment.
• With the chemotherapy drug, bendamustine, followed by Gazyva alone for follicular lymphoma (FL) in adults who did not respond to a rituximab-containing regimen, or whose FL returned after such treatment.
• In combination with chemotherapy, followed by Gazyva alone in those who responded, to treat stage II bulky, III, or IV FL in adults who have not had previous FL treatment.

Important Safety Information

The most important safety information patients should know about Gazyva

Patients must tell their doctor right away about any side effect they experience. Gazyva can cause side effects that can become serious or life-threatening, including:

• Hepatitis B Virus (HBV): Hepatitis B can cause liver failure and death. If the patient has a history of hepatitis B infection, Gazyva could cause it to return. Patients should not receive Gazyva if they have active hepatitis B liver disease. The patient’s doctor or healthcare team will need to screen them for hepatitis B before, and monitor the patient for hepatitis during and after, their treatment with Gazyva. Sometimes this will require treatment for hepatitis B. Symptoms of hepatitis include: worsening of fatigue and yellow discoloration of skin or eyes.
• Progressive Multifocal Leukoencephalopathy (PML): PML is a rare and serious brain infection caused by a virus. PML can be fatal. The patient’s weakened immune system could put them at risk. The patient’s doctor will watch for symptoms. Symptoms of PML include: confusion, difficulty talking or walking, dizziness or loss of balance, and vision problems.

Who should not receive Gazyva:

Patients should NOT receive Gazyva if they have had an allergic reaction (e.g., anaphylaxis or serum sickness) to Gazyva. Patients must tell their healthcare provider if they have had an allergic reaction to obinutuzumab or any other ingredients in Gazyva in the past.

Additional possible serious side effects of Gazyva:

Patients must tell their doctor right away about any side effect they experience. Gazyva can cause side effects that may become severe or life threatening, including:

• Infusion Reactions: These side effects may occur during or within 24 hours of any Gazyva infusion. Some infusion reactions can be serious, including, but not limited to, severe allergic reactions (anaphylaxis), acute life-threatening breathing problems, or other life-threatening infusion reactions. If the patient has a reaction, the infusion is either slowed or stopped until their symptoms are resolved. Most patients are able to complete infusions and receive medication again. However, if the infusion reaction is life-threatening, the infusion of Gazyva will be permanently stopped. The patient’s healthcare team will take steps to help lessen any side effects the patient may have to the infusion process. The patient may be given medicines to take before each Gazyva treatment. Symptoms of infusion reactions may include: fast heartbeat, tiredness, dizziness, headache, redness of the face, nausea, chills, fever, vomiting, diarrhea, rash, high blood pressure, low blood pressure, difficulty breathing, and chest discomfort.
• Hypersensitivity Reactions Including Serum Sickness: Some patients receiving Gazyva may have severe or life-threatening allergic reactions. This reaction may be severe, may happen during or after an infusion, and may affect many areas of the body. If an allergic reaction occurs, the patient’s doctor will stop the infusion and permanently discontinue Gazyva.
• Tumor Lysis Syndrome (TLS): Tumor lysis syndrome, including fatal cases, has been reported in patients receiving Gazyva. Gazyva works to break down cancer cells quickly. As cancer cells break apart, their contents are released into the blood. These contents may cause damage to organs and the heart, and may lead to kidney failure requiring the need for dialysis treatment. The patient’s doctor may prescribe medication to help prevent TLS. The patient’s doctor will also conduct regular blood tests to check for TLS. Symptoms of TLS may include nausea, vomiting, diarrhea, and tiredness.
• Infections: While the patient is taking Gazyva, they may develop infections. Some of these infections may be fatal and severe, so the patient should be sure to talk to their doctor if they think they have an infection. Patients administered Gazyva in combination with chemotherapy, followed by Gazyva alone are at a high risk of infections during and after treatment. Patients with a history of recurring or chronic infections may be at an increased risk of infection. Patients with an active infection should not be treated with Gazyva. Patients taking Gazyva plus bendamustine may be at higher risk for fatal or severe infections compared to patients taking Gazyva plus CHOP or CVP.
• Low White Blood Cell Count: When the patient has an abnormally low count of infection-fighting white blood cells, it is called neutropenia. While the patient is taking Gazyva, their doctor will do blood work to check their white blood cell count. Severe and life-threatening neutropenia can develop during or after treatment with Gazyva. Some cases of neutropenia can last for more than one month. If the patient’s white blood cell count is low, their doctor may prescribe medication to help prevent infections.
• Low Platelet Count: Platelets help stop bleeding or blood loss. Gazyva may reduce the number of platelets the patient has in their blood; having low platelet count is called thrombocytopenia. This may affect the clotting process. While the patient is taking Gazyva, their doctor will do blood work to check their platelet count. Severe and life-threatening thrombocytopenia can develop during treatment with Gazyva. Fatal bleeding events have occurred in patients treated with Gazyva. If the patient’s platelet count gets too low, their treatment may be delayed or reduced.
• Disseminated Intravascular Coagulation (DIC): Fatal and severe DIC has been reported in people receiving GAZYVA. DIC is a rare and serious abnormal blood clotting condition that should be monitored and managed by your doctor as it can lead to uncontrollable bleeding

The most common side effects of Gazyva in CLL were infusion-related reactions and low white blood cell counts.

The most common side effects seen with GAZYVA in a study that included relapsed or refractory NHL, including FL patients were infusion-related reactions, fatigue, low white blood cell counts, cough, upper respiratory tract infection, and joint or muscle pain.

The most common side effects seen with GAZYVA in a study that included previously untreated FL patients were infusion-related reactions, low white blood cell count, upper respiratory tract infections, cough, constipation and diarrhea.

Before receiving Gazyva, patients should talk to their doctor about:

• Immunizations: Before receiving Gazyva therapy, the patient should tell their healthcare provider if they have recently received or are scheduled to receive a vaccine. Patients who are treated with Gazyva should not receive live vaccines.
• Pregnancy: The patient should tell their doctor if they are pregnant, think that they might be pregnant, or plan to become pregnant. Gazyva may harm their unborn baby. The patient should speak to their doctor about using Gazyva while they are pregnant. The patient should talk to their doctor or their child’s doctor about the safety and timing of live virus vaccinations to their infant if they received Gazyva during pregnancy. Patients of childbearing potential should use effective contraception while taking Gazyva and for 6 months after your Gazyva treatment.
• Breastfeeding: Because of the potential risk of serious side reactions in breastfed children, patient should not breastfeed while taking Gazyva and for 6 months after your last dose.

Patients should tell their doctor about any side effects.

These are not all of the possible side effects of Gazyva. For more information, patients should ask their doctor or pharmacist.

Gazyva is available by prescription only.

Report side effects to the FDA at (800) FDA-1088, or http://www.fda.gov/medwatch. Report side effects to Genentech at (888) 835-2555.

Please visit https://www.Gazyva.com for the Gazyva full Prescribing Information, including BOXED WARNINGS, for additional Important Safety Information.

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.

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Source: Genentech