Saturday, Nov 9, 2019

Genentech’s Gazyva (obinutuzumab), in Combination With Standard of Care, More Than Doubles the Percentage of Lupus Nephritis Patients Achieving Complete Renal Response, Compared To Standard of Care Alone

NOBILITY Phase II study showed 40% of patients treated with Gazyva plus standard of care achieved complete renal response at week 76, compared to 18% of patients treated with placebo plus standard of care

Gazyva also met key secondary efficacy endpoints

Genentech plans to initiate enrollment in a Phase III study in 2020

South San Francisco, CA -- November 9, 2019 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced data from the Phase II NOBILITY study, investigating the safety and efficacy of Gazyva^® (obinutuzumab) for adults with proliferative lupus nephritis. The study met the primary endpoint with Gazyva, in combination with standard of care (mycophenolate mofetil or mycophenolic acid and corticosteroids), demonstrating superiority compared to placebo plus standard of care. Patients treated with Gazyva showed increasing rates of complete renal response (CRR) from week 52 to week 76, with 40% of patients in the Gazyva group achieving CRR, compared to 18% of patients in the placebo group at week 76 (p=0.007). Gazyva additionally met key secondary efficacy endpoints showing improved overall renal response (complete or partial renal responses) and serologic markers of disease activity as compared to placebo. No new safety signals were observed with Gazyva in the study at the time of this analysis. Through week 76, serious adverse events (24% vs. 29% in placebo group) and serious infections (6% vs.18% in placebo group) were not increased with Gazyva. These data will be presented at the 2019 American College of Rheumatology (ACR) Annual Meeting in Atlanta, Georgia, on November 10, 2019 (Abstract 939).

“We are very encouraged by the positive results from the NOBILITY study, which suggest that Gazyva may provide a clinically meaningful benefit for adults with proliferative lupus nephritis; a condition for which there is a strong need for more effective and targeted treatment options,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “These results support the continued development of Gazyva for people with lupus nephritis and underscore our longstanding commitment to pursue new treatment options that may benefit the lupus community.”

Lupus nephritis is a severe and potentially life-threatening manifestation of systemic lupus erythematosus resulting from inflammation of the kidneys, with proliferative lupus nephritis being the most severe form and associated with high-risk of end-stage renal disease and death. In September 2019, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to Gazyva for adults with lupus nephritis based on the Phase II NOBILITY study data. Genentech will initiate a Phase III study for Gazyva in lupus nephritis in 2020.

Phase II data from the NOBILITY study was also presented as a late-breaking oral presentation at the American Society of Nephrology’s (ASN) Kidney Week 2019 in Washington, DC, on November 8, 2019 (Abstract FR-OR136).

An audio webcast for analysts and investors on the Phase II NOBILITY study data will be held on Tuesday, November 12, 2019 from 4:30-5:30 p.m. CET / 10:30-11:30 a.m. ET. Further details are available here.

Lupus nephritis overwhelmingly impacts women, particularly young women of color. About 90% of those diagnosed with lupus are women, and African American, Hispanic, Native American and Asian American women are two to three times more likely than Caucasian women to get lupus. Genentech is committed to addressing barriers to clinical trial participation and advancing inclusive research to create new standards for clinical studies. Genentech is taking action to recruit a broader, more diverse population of participants into clinical trials, including diseases such as lupus nephritis, to ensure clinical trial participants more closely reflect those impacted by the disease for which a medicine is being studied. To learn more about Genentech’s efforts in this area, please visit https://www.gene.com/inclusiveresearch.    

About the NOBILITY Study

The Phase II, randomized, double-blind, placebo-controlled, multi-center study, NOBILITY (NCT02550652), compared the safety and efficacy of Gazyva, combined with mycophenolate mofetil (MMF) or mycophenolic acid (MPA) and corticosteroids, to placebo, combined with MMF or MPA and corticosteroids, in adult patients with ISN/RPS 2003 class III or IV proliferative lupus nephritis. The study enrolled 125 people who were randomized to receive Gazyva or placebo infusions on days 1, 15, 168, and 182. The primary endpoint was the proportion of participants who achieved a protocol-defined complete renal response (CRR) at 52 weeks. Key secondary endpoints included overall renal responses (complete or partial renal response) and serologic markers of disease activity, as compared to placebo. Patients were followed in a blinded fashion through week 104, and patients with persistent B-cell depletion are being followed for safety and continued B-cell measurements.

About Lupus Nephritis

Lupus nephritis is a severe and potentially life-threatening disorder of the kidneys. Lupus nephritis is one of the most severe manifestations of systemic lupus erythematosus (SLE), an autoimmune disease where a person's own immune system attacks healthy cells and organs, including, in the case of lupus nephritis, the kidneys. This causes kidney inflammation and may lead to blood and/or protein in the urine, high blood pressure, poor kidney function, or kidney failure. An estimated 1.5 million Americans are affected by lupus, with approximately 70% of cases representing SLE. Up to 60% of people with SLE will develop lupus nephritis, and up to 25% of people with the condition develop end-stage renal disease. Lupus overwhelmingly impacts women, particularly young women of color. About 90% of those diagnosed with lupus are women, and African American, Hispanic, Native American and Asian American women are two to three times more likely than Caucasian women to get lupus. Currently, there is no cure for lupus or lupus nephritis.

About Gazyva

Gazyva is an engineered monoclonal antibody designed to attach to CD20, a protein found only on certain types of B-cells. It is thought to work by attacking targeted cells both directly and together with the body's immune system. Gazyva is part of a collaboration between Genentech and Biogen. Combination studies investigating Gazyva with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are underway across a range of blood cancers.

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.

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.

The most common side effects of Gazyva in CLL were infusion reactions, low white blood cell counts, low platelet counts, low red blood cell counts, fever, cough, nausea, and diarrhea.

The safety of Gazyva was evaluated based on 392 patients with relapsed or refractory NHL, including FL (81%), small lymphocytic lymphoma (SLL) and marginal zone lymphoma (MZL) (a disease for which Gazyva is not indicated), who did not respond to or progressed within six months of treatment with rituximab product or a rituximab product-containing regimen. In patients with follicular lymphoma, the profile of side effects that were seen were consistent with the overall population who had NHL. The most common side effects of Gazyva were infusion reactions, low white blood cell counts, nausea, fatigue, cough, diarrhea, constipation, fever, low platelet counts, vomiting, upper respiratory tract infection, decreased appetite, joint or muscle pain, sinusitis, low red blood cell counts, general weakness and urinary tract infection.

A randomized, open-label multicenter trial (GALLIUM) evaluated the safety of Gazyva as compared to rituximab product in 1,385 patients with previously untreated follicular lymphoma (86%) or marginal zone lymphoma (14%). The most common side effects of Gazyva were infusion reactions, low white blood cell count, upper respiratory tract infection, 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, 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. It is not known if Gazyva may pass into the patient’s breast milk. The patient should speak to their doctor about using Gazyva if they are breastfeeding.

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

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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