Positive Phase III Results for Genentech’s Gazyva in Children and Young Adults With Idiopathic Nephrotic Syndrome

Monday, Oct 27, 2025

Gazyva versus mycophenolate mofetil shows significantly more children and young adults achieved sustained complete remission at week 52

If approved, Gazyva could help children and young adults sustain remission, potentially with a reduced need for steroids to manage their disease

INShore is the first global Phase III study of a targeted therapy in this chronic kidney disease commonly diagnosed in early childhood

South San Francisco, CA -- October 27, 2025 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY) announced today statistically significant and clinically meaningful results from the Phase III INShore study of Gazyva^® (obinutuzumab) in children and young adults (aged ≥ 2-25 years) with idiopathic nephrotic syndrome (INS). The study met its primary endpoint, with more people achieving sustained complete remission at one year (week 52) with Gazyva compared with mycophenolate mofetil (MMF). Sustained complete remission was defined by the absence of relapses during the study together with a low amount of protein in the urine (protein to creatine of 0.2 or less) at week 52. Certain important key secondary endpoints were also met. No new safety signals were identified and safety was in line with the well-characterized profile of Gazyva in adults.

"These results show that Gazyva may achieve robust disease control with a reduced need for corticosteroids, which are associated with serious side effects over time," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "Idiopathic nephrotic syndrome is a severe and chronic kidney disease usually diagnosed in early childhood, yet meaningful treatment progress has been limited. As a targeted therapy, Gazyva has the potential to help address this unmet need and we look forward to sharing the data with health authorities."

For several decades, treatment for idiopathic nephrotic syndrome has primarily relied on steroids yet relapse rates remain high and long-term use is limited by serious side effects. Newer approaches that target specific immune cells - such as B cells, thought to be a key driver of disease activity - may help control symptoms more effectively.

Analysis of key secondary endpoints showed statistically significant and clinically meaningful benefits with Gazyva with an increase in those with overall relapse-free survival (RFS), median time to relapse or death, reduction in cumulative corticosteroid dose from baseline to week 52, and fewer relapses from baseline to week 52, all compared with MMF. Other key secondary endpoints showed no significant difference with Gazyva versus MMF.*

Data will be presented at an upcoming medical meeting and shared with health authorities, including the U.S. Food and Drug Administration and the European Medicines Agency.

INShore data add to a growing body of evidence, including the Phase III REGENCY study in lupus nephritis, that shows targeting disease-causing B cells with Gazyva may help address disease activity across a spectrum of immune-mediated kidney and kidney-related diseases. In October 2025, Gazyva was approved in the U.S. for the treatment of adults with active lupus nephritis who are receiving standard therapy, based on data from the Phase III REGENCY and Phase II NOBILITY studies.

In addition to idiopathic nephrotic syndrome, Gazyva is being investigated in membranous nephropathy, lupus nephritis, rare immune-mediated kidney diseases and systemic lupus erythematosus, an autoimmune disease that can lead to lupus nephritis, as part of our ambition to be leaders in immune-mediated kidney and kidney-related diseases.

About Gazyva

Gazyva^® (obinutuzumab) is a Type II engineered humanized monoclonal antibody designed to attach to CD20, a protein found on certain types of B cells. Gazyva is approved for adults with lupus nephritis who are receiving standard therapy in the U.S. 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. In the U.S., Gazyva is part of a collaboration between Genentech and Biogen.

About the INShore Study

INShore [NCT05627557] is a Phase III open-label, randomized, multicenter study investigating Gazyva^® (obinutuzumab) compared with mycophenolate mofetil (MMF) in children and young adults in clinical remission (aged ≥2-25 years) with frequently relapsing or steroid-dependent nephrotic syndrome. The study enrolled 85 children or young adults who were randomized 1:1 to receive Gazyva at weeks 0, 2, 24 and 26, or MMF daily. The primary endpoint is the percentage of participants with sustained complete remission at one year (week 52).

About Idiopathic Nephrotic Syndrome

Idiopathic nephrotic syndrome is a rare kidney-related autoimmune disease, usually diagnosed in early childhood. It is characterized by unpredictable relapses that cause fatigue, swelling, weight gain and increased susceptibility to infections and clotting, as well as anxiety, depression and reduced self-esteem, brought on by the fear of relapse and social isolation. The current mainstay of treatment is steroids, however relapse rates remain high (>70%) and the serious side effects limit long-term use.

There is an urgent need for new targeted treatment approaches that can sustain remission and reduce the physical and psychosocial burden of the disease.

GAZYVA 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
• 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
• for the treatment of adult patients with active lupus nephritis (LN) who are receiving standard therapy

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:

Patientsshould 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-Related Reactions: Theseside effects may occur during or within 24 hours of any GAZYVA infusion. Some infusion-related reactions can be serious, including, but not limited to, severe allergic reactions (anaphylaxis), acute life-threatening breathing problems, or other life-threatening infusion-related 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-related 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-related 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. TLS is not identified as a risk in LN
• Serious, Including Fatal, 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 taking GAZYVA plus standard therapy may be at higher risk for fatal or severe infections compared to patients taking standard therapy plus placebo. 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. If the patient develops a serious infection, your doctor will immediately discontinue GAZYVA and begin treatment for the infection.
• 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 the patient's 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.

The most common side effects of GAZYVA in LN were upper respiratory tract infection, COVID-19, urinary tract infection, bronchitis, pneumonia, infusion infusion-related reactions, and neutropenia.

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, plan to become pregnant, or are breastfeeding. 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. Women 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, patients 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, orhttp://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 Immunology

Genentech is committed to harnessing pioneering science and innovation to address critical unmet needs for patients with immune-mediated inflammatory diseases. Our pipeline includes over a dozen clinical programs in immunology aiming to transform care for people living with lupus, MASH, ulcerative colitis, Crohn's disease, immunoglobulin A nephropathy, idiopathic nephrotic syndrome, atopic dermatitis, and rheumatoid arthritis. We are investing end-to-end in immunology from discovery and R&D to commercialization across a variety of modalities including monoclonal antibodies, bispecifics, and CAR-T cell therapies to help solve some of the most difficult challenges in immunology today.

About Genentech

Founded nearly 50 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.

*Sustained complete remission (week 76), probability of relapse free survival (week 52), proportion of participants experiencing edema associated relapse (during 52 week treatment period), mean change in CureGN Edema scale (from baseline to week 52), mean change in "General Fatigue" domain of PedsQL-Multidimensional Fatigue Scale total score (from baseline to week 52), mean change in "Physical Functioning" domain of PedsQL (from baseline to week 52).

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