Gazyva® (obinutuzumab)

Gazyva® (obinutuzumab) is a medicine that is designed to work with the body’s own immune system to attack a type of blood cell called B-cells that have a certain marker on their surface (CD20).1

Follicular lymphoma and chronic lymphocytic leukemia (CLL) are two of the most common types of blood cancers. These cancers result from abnormal B-cells.2, 3, 4

Gazyva was the first medicine approved under the U.S. Food and Drug Administration’s (FDA’s) Breakthrough Therapy Designation program.5

Approved Indications

Gazyva is FDA-approved for the following indications:1

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

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. Symptom 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.

What is Follicular Lymphoma?

Follicular lymphoma is the most common slow-growing form of non-Hodgkin’s lymphoma (NHL).6 It is considered incurable and relapse is common.7

  • ABOUT 1 IN 5

    CASES OF NHL ARE FOLLICULAR LYMPHOMA.6

  • 14,448

    ESTIMATED NEW CASES OF FOLLICULAR LYMPHOMA IN THE U.S. IN 2017.6, 8

What is Chronic Lymphocytic Leukemia?

Chronic lymphocytic leukemia (CLL) is a slow-growing cancer of the blood and bone marrow that is generally considered incurable.9, 10 It is the most common form of adult leukemia.4

  • 20,110

    ESTIMATED NEW CASES OF CLL AND 4,660 DEATHS FROM THE DISEASE IN THE U.S. IN 2017.11

How Gazyva is Believed to Work (Mechanism of Action)1

Gazyva is an engineered monoclonal antibody that targets the CD20 molecule found on B-cells. In addition to cancer cells, Gazyva can also harm healthy cells in the body. It is thought to work in the following ways:1, 12, 13

Gazyva Efficacy and Safety Profiles1

Follicular Lymphoma

GALLIUM STUDY
The FDA approval of Gazyva in combination with chemotherapy (CHOP, CVP or bendamustine) as an initial treatment for adults with previously untreated stage II bulky, III or IV follicular lymphoma, followed by Gazyva alone for those who achieved at least a partial remission, was based on data from the pivotal Phase III GALLIUM study. The study compared the Gazyva-based treatment regimen to rituximab plus chemotherapy followed by rituximab alone.

Safety was evaluated based on 1,385 people with previously untreated follicular lymphoma (86 percent) or marginal zone lymphoma (14 percent). The most common Grade 3-5 adverse reactions (incidence ≥5%) observed more frequently in the Gazyva arm were low white blood cell count (neutropenia), infusion reactions, low white blood cell count with fever (febrile neutropenia) and low platelet count (thrombocytopenia). The most common adverse reactions (incidence ≥20%) observed at least 2% more in the Gazyva arm were infusion reactions, low white blood cell count (neutropenia), upper respiratory tract infection, cough, constipation and diarrhea.

GADOLIN STUDY
The FDA approval of Gazyva in combination with bendamustine, followed by Gazyva alone, for follicular lymphoma in adults who did not respond to a rituximab-containing regimen or whose follicular lymphoma returned after such treatment (“rituximabrefractory” disease) was based on data from the pivotal Phase III GADOLIN study, which compared the Gazyva-based treatment regimen to bendamustine alone in people with follicular lymphoma whose disease did not respond to or progressed within 6 months of treatment with a rituximab-containing regimen.

Safety was evaluated based on 392 people with NHL, of whom 81 percent had follicular lymphoma. In people with follicular lymphoma, the safety profile was consistent with the overall NHL population. The most common Grade 3-4 adverse reactions (incidence ≥10%) observed in the Gazyva arm were low white blood cell count (neutropenia), low platelet count (thrombocytopenia) and infusion reactions. The most common adverse reactions (incidence ≥10%) observed in the Gazyva arm were infusion reactions, low white blood cell count (neutropenia), nausea, fatigue, cough, diarrhea, constipation, fever (pyrexia), low platelet count (thrombocytopenia), vomiting, upper respiratory tract infection, decreased appetite, joint or muscle pain (arthralgia), sinusitis, low red blood cell count (anemia), general weakness (asthenia) and urinary tract infection.

Chronic Lymphocytic Leukemia

CLL11 STUDY
The FDA approval of Gazyva plus clb to treat CLL in adults who have not had previous CLL treatment was based on data from the pivotal Phase III CLL11 study. The first stage of the study compared Gazyva plus clb to clb alone, and the second stage compared Gazyva plus clb to rituximab plus clb.

The most common Grade 3-4 adverse reactions (incidence ≥10%) observed in the Gazyva arm were low white blood cell counts (neutropenia), infusion reactions and low platelet count (thrombocytopenia). The most common adverse reactions (incidence ≥10%) in the Gazyva arm were infusion reactions, low white blood cell count (neutropenia), low platelet count (thrombocytopenia), low red blood cell count (anemia), fever (pyrexia), cough, nausea and diarrhea.

What it Treats

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.

GAZYVA® (obinutuzumab) is a prescription medicine used 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.

GAZYVA® (obinutuzumab) is a prescription medicine used in combination with chemotherapy, followed by GAZYVA alone in those who responded, to treat stage II bulky, III, or IV follicular lymphoma (FL) in adults who have not had previous FL treatment.

Important Safety Information

What is the most important safety information I should know about GAZYVA?

Tell your doctor right away about any side effect you 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 you have a history of hepatitis B infection, GAZYVA could cause it to return. You should not receive GAZYVA if you have active hepatitis B liver disease. Your doctor or healthcare team will need to screen you for hepatitis B before, and monitor you during and after, your 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. Your weakened immune system could put you at risk. Your 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?

  • Do NOT receive GAZYVA if you have had an allergic reaction (e.g., anaphylaxis or serum sickness) to GAZYVA. Tell your healthcare provider if you have had an allergic reaction to obinutuzumab or any other ingredients in GAZYVA in the past

What are the additional possible serious side effects of GAZYVA?

Tell your doctor right away about any side effect you 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 you have a reaction, the infusion is either slowed or stopped until your 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. Your healthcare team will take steps to help lessen any side effects you may have to the infusion process. You 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 people 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, your 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. Your doctor may prescribe medication to help prevent TLS. Your doctor will also conduct regular blood tests to check for TLS. Symptoms of TLS may include nausea, vomiting, diarrhea, and tiredness
  • Infections: While you’re taking GAZYVA, you may develop infections. Some of these infections may be fatal and severe, so be sure to talk to your doctor if you think you 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 you have an abnormally low count of infection-fighting white blood cells, it is called neutropenia. While you are taking GAZYVA, your doctor will do blood work to check your 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 your white blood cell count is low, your 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 you have in your blood; having low platelet count is called thrombocytopenia. This may affect the clotting process. While you are taking GAZYVA, your doctor will do blood work to check your platelet count. Severe and life-threatening thrombocytopenia can develop during treatment with GAZYVA. Fatal bleeding events have occurred in patients treated with GAZYVA. If your platelet count gets too low, your 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 6 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

What other information should I tell my doctor before receiving GAZYVA?

You should talk to your doctor about:

  • Immunizations: Before receiving GAZYVA therapy, tell your healthcare provider if you have recently received or are scheduled to receive a vaccine. People who are treated with GAZYVA should not receive live vaccines
  • Pregnancy: Tell your doctor if you are pregnant, think that you might be pregnant, plan to become pregnant, or are breastfeeding. GAZYVA may harm your unborn baby. Speak to your doctor about using GAZYVA while you are pregnant. Talk to your doctor or your child’s doctor about the safety and timing of live virus vaccinations to your infant if you received GAZYVA during pregnancy. It is not known if GAZYVA may pass into your breast milk. Speak to your doctor about using GAZYVA if you are breastfeeding

Tell your doctor about any side effects.

These are not all of the possible side effects of GAZYVA. For more information, ask your doctor or pharmacist.

GAZYVA is available by prescription only.

You may report side effects to the FDA at (800) FDA-1088, or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

Please see the accompanying full Prescribing Information, including BOXED WARNINGS, for additional Important Safety Information

References

  1. Gazyva (obinutuzumab) Injection Prescribing Information. Genentech, Inc. December 2017.
  2. Kalil N and Cheson B. Chronic Lymphocytic Leukemia. The Oncologist. 1999; 4: 352-369.
  3. Harris N L, Stein H, Coupland S E, et al. New approaches to lymphoma diagnosis. Haematology. January 1, 2001. DOI: 10.1182/asheducation-2001.1.194.
  4. Byrd J. Introduction to a Series of Reviews on Chronic Lymphocytic leukemia (CLL). Blood. June 11, 2015. DOI: 10.1182/blood-2015-06-639161.
  5. U.S. Food and Drug Administration. Previous Cumulative CY CDER BT Approvals. https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/DrugandBiologicApprovalReports/NDAandBLAApprovalReports/UCM481542.pdf. Accessed October 25, 2017.
  6. National Cancer Institute. Adult Non-Hodgkin Lymphoma Treatment – for health professionals (PDQ®). http://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq. Accessed September 25, 2017.
  7. Ghielmini M. Follicular Lymphoma. Ann Oncol. October 2010. DOI:10.10963/annonc/mdq287.
  8. National Cancer Institute. SEER Cancer Statistics Factsheets: Non-Hodgkin Lymphoma. http://seer.cancer.gov/statfacts/html/nhl.html. Accessed September 25,2017.
  9. National Cancer Institute. Chronic Lymphocytic Leukemia Treatment (PDQ®). http://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq. Accessed September 25, 2017.
  10. Dighiero G and Hamblin T. Chronic Lymphocytic Leukemia. The Lancet. 2008; 371:1017-1029.
  11. National Cancer Institute. SEER Cancer Statistics Factsheets: Chronic Lymphocytic Leukemia. http://seer.cancer.gov/statfacts/html/clyl.html. Accessed September 25, 2017.
  12. Mossner E, Brunker P, Moser S, et al. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell–mediated B-cell cytotoxicity. Blood. June 3, 2010; 115(22):4393-4402.
  13. Herter S, Herting F, Mundigl O, et al. Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab in vitro and in xenograft models. Mol Cancer Ther. 2013;12(10):2031-2042.