FDA Approves Genentech's Gazyva® (Obinutuzumab) for Certain People with Previously Treated Follicular Lymphoma

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) approved Gazyva^® (obinutuzumab) plus bendamustine chemotherapy followed by Gazyva alone as a new treatment for people with follicular lymphoma who did not respond to a Rituxan^® (rituximab)-containing regimen, or whose follicular lymphoma returned after such treatment. Follicular lymphoma is the most common type of indolent (slow-growing) non-Hodgkin’s lymphoma (NHL) and accounts for approximately one in five cases of NHL.

“People with follicular lymphoma whose disease returns or worsens despite treatment with a Rituxan-containing regimen need more options because the disease becomes more difficult to treat each time it comes back,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “Gazyva plus bendamustine provides a new treatment option that can be used after relapse to significantly reduce the risk of progression or death.”

The approval is based on results from the Phase III GADOLIN study, which showed that, in people with follicular lymphoma whose disease progressed during or within six months of prior Rituxan-based therapy, Gazyva plus bendamustine followed by Gazyva alone demonstrated a 52 percent reduction (HR=0.48, 95 percent CI 0.34-0.68, p<0.0001) in the risk of disease worsening or death (progression-free survival, PFS), compared to bendamustine alone, as assessed by an independent review committee (IRC). The supplemental Biologics License Application based on these data was granted Priority Review, a designation granted to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease.

The safety of Gazyva was evaluated based on 392 people in the GADOLIN study with indolent NHL of whom 81 percent had follicular lymphoma. The most common Grade 3-4 side effects of this Gazyva regimen were low white blood cell counts, infusion reactions and low platelet counts. The most common side effects of this Gazyva regimen 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.

With this approval, Gazyva is approved in the United States to treat two common types of blood cancer. Gazyva is also approved in combination with chlorambucil for people with previously untreated chronic lymphocytic leukemia (CLL) based on data from the pivotal CLL11 study, which compared Gazyva plus chlorambucil head-to-head with Rituxan plus chlorambucil.

Marketing applications for Gazyva based on the GADOLIN study results have also been submitted to other regulatory authorities, including the European Medicines Agency (EMA), for approval consideration.

For those who qualify, Genentech offers patient assistance programs for people taking Gazyva through Genentech Access Solutions.

About the GADOLIN Study

GADOLIN (NCT01059630; GA04753g) is a Phase III open-label, multicenter, randomized two-arm study evaluating Gazyva plus bendamustine followed by Gazyva alone until disease progression or for up to two years compared to bendamustine alone. GADOLIN included 413 patients with indolent (slow-growing) non-Hodgkin’s lymphoma (NHL), including 321 patients with follicular lymphoma, whose disease progressed during or within six months of prior Rituxan-based therapy. The primary endpoint of the study is progression-free survival (PFS) as assessed by an independent review committee (IRC), with secondary endpoints including PFS as assessed by investigator review, best overall response (BOR), complete response (CR), partial response (PR), duration of response, overall survival (OS) and safety profile. Results in follicular lymphoma showed:

• The Gazyva regimen improved PFS compared to bendamustine alone, as assessed by IRC (HR=0.48, 95 percent CI 0.34-0.68, p<0.0001). Median PFS was not reached in those receiving the Gazyva regimen versus 13.8 months in those receiving bendamustine alone.
• Investigator-assessed PFS was consistent with IRC-assessed PFS. As assessed by investigator review, median PFS with the Gazyva regimen was more than double that with bendamustine alone (29.2 months vs. 13.7 months; HR=0.48, 95 percent CI 0.35-0.67, p<0.0001).
• In addition, BOR for those receiving the Gazyva regimen was 78.7 percent (15.5 percent CR, 63.2 percent PR) compared to 74.7 percent for those receiving bendamustine alone (18.7 percent CR, 56 percent PR), as assessed by IRC.
• The median duration of response was not reached for those receiving the Gazyva regimen and was 11.6 months for those receiving bendamustine alone.

• The Gazyva regimen reduced the risk of death (OS) by 38 percent compared to bendamustine alone based on a post-hoc analysis with 24.1 months of median observation time (HR=0.62, 95 percent CI 0.39-0.98). The median OS has not yet been reached in either study arm.
• The most common Grade 3-4 side effects observed in those receiving the Gazyva regimen were low white blood cell counts (33 percent), infusion reactions (11 percent) and low platelet counts (10 percent). The most common side effects were infusion reactions (69 percent), low white blood cell counts (35 percent), nausea (54 percent), fatigue (39 percent), cough (26 percent), diarrhea (27 percent), constipation (19 percent), fever (18 percent), low platelet counts (15 percent), vomiting (22 percent), upper respiratory tract infection (13 percent), decreased appetite (18 percent), joint or muscle pain (12 percent), sinusitis (12 percent), low red blood cell counts (12 percent), general weakness (11 percent) and urinary tract infection (10 percent).

About Follicular Lymphoma

Follicular lymphoma is the most common indolent (slow-growing) form of non-Hodgkin’s lymphoma (NHL), accounting for about one in five cases of NHL. It is considered incurable and relapse is common. In the United States, it was estimated that more than 14,000 new cases of follicular lymphoma would be diagnosed in 2015.

About Genentech Access Solutions

Access Solutions is part of Genentech’s commitment to helping people access the Genentech medicines they are prescribed, regardless of their ability to pay. The team of 350 in-house specialists at Access Solutions is dedicated to helping people navigate the access and reimbursement process, and to providing assistance to eligible patients in the United States who are uninsured or cannot afford the out-of-pocket costs for their medicine. To date, the team has helped more than 1.2 million patients access the medicines they need. Please contact Access Solutions (866) 4ACCESS/(866) 422-2377 or visit http://www.Genentech-Access.com for more information.

About Gazyva

Gazyva is an engineered monoclonal antibody designed to attach to CD20, a protein found only on B-cells. It attacks targeted cells both directly and together with the body's immune system. Gazyva was discovered by Roche Glycart AG, a wholly owned, independent research unit of Roche. In the United States, Gazyva is part of a collaboration between Genentech and Biogen.

Gazyva is being studied in a large clinical program, including the Phase III GOYA and GALLIUM studies. GOYA is comparing Gazyva head-to-head with Rituxan plus CHOP chemotherapy in first line diffuse large B-cell lymphoma (DLBCL) and GALLIUM is comparing Gazyva plus chemotherapy head-to-head with Rituxan plus chemotherapy in first line indolent non-Hodgkin’s lymphoma (NHL). Additional combination studies investigating Gazyva with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are planned or underway across a range of blood cancers.

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.

Important Safety Information

Patients must tell their doctor right away about any side effects 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 a patient has had 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 for hepatitis B before, and monitor the patient for hepatitis during and after, 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. A patient’s weakened immune system could put the patient 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.

Additional possible serious side effects of Gazyva:

Patients must tell their doctor right away about any side effects 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 a patient has a reaction, the infusion is either slowed or stopped until the patient’s symptoms are resolved. Most patients are able to complete infusions and receive medication again. However, if the infusion reaction is serious, 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. Signs of infusion reactions may include: tiredness, dizziness, headache, redness of the face, nausea, chills, fever, vomiting, diarrhea, breathing problems, and chest pain

• 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 a patient is taking Gazyva, the patient may develop infections. Some of these infections may be severe. Fatal infections have been reported, so the patient should be sure to talk to the doctor if the patient thinks the patient has one. Patients with active infection should not be treated with Gazyva. The patient’s risk for infections may continue even after the patient stops taking Gazyva. The patient’s doctor may prescribe medications to help prevent infections. Symptoms of infection include fever and cough
• Low White Blood Cell Count: When a patient has an abnormally low count of infection-fighting white blood cells, it is called neutropenia. While the patient is taking Gazyva, the patient’s doctor will do blood work to check the patient’s white blood cell counts. 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 a patient’s white blood cell count is low, the patient’s 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 the blood; having low platelet count is called thrombocytopenia. This may affect the clotting process. While the patient is taking Gazyva, the patient’s doctor will do blood work to check the patient’s platelet count. Severe and life-threatening thrombocytopenia can develop during or after treatment with Gazyva. If the patient’s platelet count gets too low, the treatment may be delayed or reduced

Most common side effects of Gazyva

The most common side effects of Gazyva in CLL are 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 indolent NHL (iNHL) of whom 81 percent had follicular lymphoma. In patients with follicular lymphoma, the most common side effects that were seen were consistent with the overall population who had iNHL. The most common side effects of Gazyva are 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.

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

Immunizations: Before receiving Gazyva therapy, the patient should tell the patient’s healthcare provider if the patient has recently received or is scheduled to receive a vaccine. Patients who are treated with Gazyva should not receive live vaccines.

Pregnancy: A patient should tell the doctor if the patient is pregnant, plans to become pregnant, or is breastfeeding. Gazyva may harm the unborn baby. Mothers who have been exposed to Gazyva during pregnancy should discuss the safety and timing of live virus vaccinations for their infants with their child’s healthcare providers. It is not known if Gazyva may pass into the patient’s breast milk. The patient should speak to the doctor about using Gazyva if the patient is breastfeeding.

Patients must 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.

Rituxan Indications

Rituxan (rituximab) is indicated for the treatment of patients with:

• Low-grade or follicular CD20-positive non-Hodgkin’s lymphoma as a single-agent therapy in patients whose disease recurred or did not respond to initial treatment
• Follicular CD20-positive non-Hodgkin’s lymphoma as an initial treatment with chemotherapy, and in patients whose initial treatment was successful, as a single-agent follow-up therapy
• Low-grade or follicular CD20-positive non-Hodgkin’s lymphoma as a single-agent follow-up therapy for patients who responded to initial treatment with CVP chemotherapy

• CD20-positive diffuse large B-cell non-Hodgkin’s lymphoma as an initial treatment in combination with CHOP chemotherapy
• CD20-positive chronic lymphocytic leukemia in combination with FC chemotherapy as an initial treatment or as a treatment after disease has recurred

People with serious infections should not receive Rituxan.

Important Safety Information:

Patients must tell their doctor right away about any side effects they experience. Rituxan can cause serious side effects that can lead to death, including:

• Infusion Reactions: may occur during or within 24 hours of the infusion. The patient’s doctor should give the patient medicines before their treatment. Symptoms can include hives, rash, itching, facial or oral swelling, sudden cough, shortness of breath, difficulty breathing, weakness, dizziness, feeling faint, racing heart or chest pain.

• Severe Skin and Mouth Reactions: symptoms can include painful sores, ulcers, or blisters on the skin, lips or mouth; peeling skin; rash; or pustules.
• Hepatitis B Virus (HBV) Reactivation: may cause serious liver problems including liver failure and death. If patients have had hepatitis B or are carriers of HBV, receiving Rituxan could cause the virus to become an active infection again. Patients should not receive Rituxan if they have active HBV liver disease. The patient’s doctor will do blood tests to check for HBV infection prior to treatment and will monitor the patient during and for several months following their treatment.
• Progressive Multifocal Leukoencephalopathy (PML): a rare, serious brain infection that can lead to severe disability and death and for which there is no known prevention, treatment or cure. Symptoms can include difficulty thinking, loss of balance, changes in speech or walking, weakness on one side of the body or blurred or lost vision.

What are the additional possible serious side effects of Rituxan?

Patients must tell their doctor right away about any side effects they experience. Rituxan can cause serious side effects that can lead to death, including:

• Tumor Lysis Syndrome (TLS): may cause kidney failure and the need for dialysis treatment, abnormal heart rhythm and can lead to death. The patient’s doctor may give the patient medicines before their treatment to help prevent TLS.
• Serious Infections: can happen during and after treatment and can lead to death. These infections may be bacterial, fungal or viral. Symptoms can include fever; cold or flu symptoms; earache or headache; pain during urination; white patches in the mouth or throat; cuts or scrapes that are red, warm, swollen or painful.

• Heart Problems: symptoms can include chest pain and irregular heartbeats that may require treatment. The patient’s doctor may need to stop their treatment.
• Kidney Problems: the patient’s doctor should do blood tests to check how well the patient’s kidneys are working.
• Stomach and Serious Bowel Problems: can include blockage or tears in the bowel that can lead to death. Stomach area pain during treatment can be a symptom.
• Low Blood Cell Counts: the patient’s blood cell counts may be monitored during treatment.

The most common side effects of Rituxan are infusion reactions, chills, infections, body aches, tiredness and low white blood cells.

Patients must tell their doctor if they are pregnant, plan to become pregnant or are breastfeeding. It is not known if Rituxan may harm the patient’s unborn baby or pass into the patient’s breast milk. Women should use birth control while using Rituxan and for 12 months after treatment.

Patients must tell their doctor about any side effect that bothers them or that does not go away.

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

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.Rituxan.com for the Rituxan full Prescribing Information, including Boxed WARNINGS and Medication Guide, for additional Important Safety Information.

About Genentech In Hematology

For more than 20 years, Genentech has been developing medicines with the goal to redefine treatment in hematology. Today, we’re investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. In addition to approved medicines Rituxan^® (rituximab) and Gazyva^® (obinutuzumab), Genentech’s pipeline of investigational hematology medicines includes an anti-PDL1 antibody (atezolizumab/MPDL3280A), an anti-CD79b antibody drug conjugate (polatuzumab vedotin/RG7596), a small molecule antagonist of MDM2 (idasanutlin/RG7388) and in collaboration with AbbVie, a small molecule BCL-2 inhibitor (venetoclax/RG7601/GDC-0199/ABT-199). Genentech’s dedication to developing novel medicines for blood diseases expands beyond oncology, with the development of the investigational hemophilia A treatment emicizumab (ACE910).

About Genentech

Founded 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or 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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