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Sunday, Dec 4, 2016

Genentech’s Gazyva Helped People With Previously Untreated Follicular Lymphoma Live Significantly Longer without their Disease Worsening Compared to Rituxan

  • First Phase III study to show superior progression-free survival compared to Rituxan-based standard of care treatment for most common slow-growing form of non-Hodgkin’s lymphom
  • Results will be presented during the Plenary Scientific Session at 58th American Society of Hematology Annual Meeting

South San Francisco, CA -- December 4, 2016 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced data from the positive, pivotal Phase III GALLIUM study that compared Gazyva® (obinutuzumab) plus chemotherapy followed by Gazyva alone head-to-head against Rituxan® (rituximab) plus chemotherapy followed by Rituxan alone for people with previously untreated follicular lymphoma. At a pre-planned interim analysis in May 2016, an independent data monitoring committee determined that the study met its primary endpoint early. The results showed Gazyva-based treatment reduced the risk of disease worsening or death (progression-free survival; PFS, as assessed by investigator) by 34 percent compared to Rituxan-based treatment (HR=0.66; 95% CI 0.51-0.85, p=0.0012). Median PFS was not yet reached. Adverse events with either Gazyva or Rituxan were consistent with those seen in previous studies.

"Follicular lymphoma, the most common slow-growing form of non-Hodgkin’s lymphoma, is an incurable blood cancer characterized by cycles of remission and disease progression, and becomes harder to treat with every relapse," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "This study of Gazyva-based treatment is the first and only Phase III trial to date to show superior progression-free survival compared to Rituxan-based treatment, the current standard of care, in previously untreated follicular lymphoma."

The primary results from the GALLIUM study (Abstract #6) will be presented during the Plenary Scientific Session of the 58th American Society of Hematology (ASH) Annual Meeting in San Diego by Dr. Robert Marcus, King’s College Hospital, London and the National Cancer Research Institute (NCRI), on Sunday, December 4 at 2:00 P.M. PST. Additionally, an analysis of minimal residual disease (MRD) status in the GALLIUM study (Abstract #613) will be presented in a separate oral session by Dr. Christiane Pott, University Hospital Schleswig-Holstein, Kiel, Germany, and the German Low Grade Lymphoma Study Group (GLSG) on Monday, December 5 at 7:00 A.M. PST.

GALLIUM is the third positive Phase III study for Gazyva, following the CLL11 study in patients with previously untreated chronic lymphocytic leukemia (CLL) and the GADOLIN study in patients with indolent (slow-growing) non-Hodgkin’s lymphoma whose disease progressed during or within six months of prior Rituxan-based therapy. The results of the GALLIUM study will be submitted to health authorities around the world for approval consideration.

About the GALLIUM study

GALLIUM (NCT01332968) is a global Phase III open-label, multicenter, randomized two-arm study examining the efficacy and safety of Gazyva plus chemotherapy followed by Gazyva alone for up to two years, as compared head-to-head against Rituxan plus chemotherapy followed by Rituxan alone for up to two years. Chemotherapies used were CHOP, CVP or bendamustine and were selected by each participating study site prior to beginning enrollment. GALLIUM included 1401 patients with previously untreated indolent non-Hodgkin’s lymphoma (iNHL), of which 1202 patients had follicular lymphoma. The primary endpoint of the study was investigator-assessed PFS in patients with follicular lymphoma, with secondary endpoints including PFS assessed by independent review committee (IRC), PFS in the overall study population (iNHL), response rate (overall response, ORR; and complete response, CR), overall survival (OS) and safety. The GALLIUM study is being conducted in cooperation with the GLSG (Germany), the East German Study Group Hematology and Oncology (OSHO; Germany) and the NCRI (United Kingdom).

A summary of the GALLIUM study results presented at ASH is included below.

Study Group

Patients with previously untreated follicular lymphoma

Treatment Group

Gazyva + chemotherapy, followed by Gazyva alone

Rituxan + chemotherapy,

followed by Rituxan alone

N=

601

601

PFS (primary and secondary endpoints)1

PFS

Investigator: HR=0.66 (0.51, 0.85), p=0.0012

Independent: HR=0.71 (0.54, 0.93), p=0.0138

PFS Rate at 3 Years

Investigator: 80.0%

Independent: 81.9%

Investigator: 73.3%

Independent: 77.9%

OS (secondary endpoint)

OS

HR=0.75 (0.49, 1.17), p=0.21

OS Rate at 3 Years

94.0%

92.1%

Time to Next Treatment (TTNT; secondary endpoint)

TTNT

HR=0.68 (0.51, 0.91), p=0.0094

TTNT at 3 Years

87.1%

81.2%

Response Rates (at end of induction; secondary endpoints)2

ORR

88.5%

86.9%

CR

19.5%

23.8%

Partial Response (PR)

69.1%

63.1%

Minimal Residual Disease (MRD; exploratory endpoint) [Pott et al.]

N=

351

345

MRD-Negativity3 (in blood and/or bone marrow at end of treatment with Gazyva or Rituxan plus chemotherapy)

92.0%

84.9%

p=0.0041

Safety (secondary endpoint)

N=

595

597

Adverse Events (AEs)

  • AEs observed with Gazyva and Rituxan were consistent with those seen in previous clinical trials when each was combined with various chemotherapies.
  • The overall rate of Grade 3 or higher AEs occurring in the Gazyva and Rituxan arms was 74.6% and 67.8%, respectively.
  • The most common Grade 3 or higher AEs that occurred more often in the Gazyva versus Rituxan arm were low white blood cell counts (neutropenia, 43.9% vs. 37.9%; leukopenia, 8.6% vs. 8.4%), low white blood cell count with fever (febrile neutropenia, 6.9% vs. 4.9%), infusion-related reactions4 (12.4% vs. 6.7%), low platelet count (thrombocytopenia, 6.1% vs. 2.7%), infections (20.0% vs. 15.6%) and second neoplasms (4.7% vs. 2.7%).
  • Fatal AEs occurred in 4.0% of people in the Gazyva arm compared to 3.4% of people in the Rituxan arm.

1 Primary endpoint is PFS as assessed by investigator; median follow-up of 34.5 months

2 Measured by computerized tomography (CT) scans

3 MRD-negativity means no cancer can be detected in the blood or bone marrow using a specific highly sensitive test

4 Defined as any AE occurring during or within 24 hours of infusion of Gazyva or Rituxan and considered drug-related

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 is estimated that more than 14,000 new cases of follicular lymphoma will be diagnosed in 2016.

About Gazyva

Gazyva is an engineered monoclonal antibody designed to attach to CD20, a protein found 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 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.

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 CD20-positive non-Hodgkin’s lymphoma as a single-agent follow-up therapy for patients who did not progress on 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.

It is not known if Rituxan is safe or effective in children.

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, Genentech’s pipeline of investigational hematology medicines includes an anti-CD79b antibody drug conjugate (polatuzumab vedotin/RG7596) and a small molecule antagonist of MDM2 (idasanutlin/RG7388). Genentech’s dedication to developing novel medicines for blood diseases expands beyond oncology, with the development of the investigational hemophilia A treatment emicizumab (ACE910). For more information visit http://www.gene.com/hematology.

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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