FDA Grants Priority Review for Genentech’s Gazyva in Previously Untreated Follicular Lymphoma
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the U.S. Food and Drug Administration
(FDA) has accepted the company’s supplemental Biologics License Application (sBLA) and granted Priority Review for
Gazyva® (obinutuzumab) in combination with chemotherapy followed by Gazyva alone for people with previously untreated
follicular lymphoma, one of the most common blood cancers among adults. Follicular lymphoma, a slow-growing (indolent) form of
non-Hodgkin’s lymphoma, is incurable and characterized by cycles of remission and relapse.
“Follicular lymphoma becomes harder to treat each time it returns, and the goal of initial treatment is to prevent the cancer
from progressing for as long as possible,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development.
“Based on the GALLIUM study, Gazyva-based treatment significantly improved progression-free survival over the current standard of
care, and we are committed to bringing this potential new option to patients as soon as possible.”
The sBLA is based on results of the GALLIUM study, which is the first Phase III study in previously untreated follicular
lymphoma to show superior progression-free survival (PFS) over Rituxan® (rituximab)-based treatment, the current
standard of care. Adverse events (AEs) with either Gazyva or Rituxan were consistent with those seen in previous studies.
The FDA is expected to make a decision on approval under Priority Review by December 23, 2017. Priority Review designation is
granted to medicines that the FDA has determined to have the potential to provide significant improvements in the safety and
effectiveness of the treatment, prevention or diagnosis of a serious disease. Additional submissions of the GALLIUM data to health
authorities around the world are ongoing.
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 1,401 patients with previously untreated indolent
non-Hodgkin’s lymphoma (iNHL), of which 1,202 patients had follicular lymphoma. The primary endpoint of the study was
investigator-assessed progression-free survival (PFS) in patients with follicular lymphoma, with secondary endpoints including PFS
assessed by independent review committee (IRC) in patients with follicular lymphoma, PFS in the overall study population (iNHL),
response rate (overall response, ORR; and complete response, CR), overall survival (OS) and safety. The 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). Results after a follow-up period of 41.1 months showed:
- Gazyva-based treatment reduced the risk of disease worsening or death (PFS, as assessed by
investigator) by 32 percent compared to Rituxan-based treatment (HR=0.68; 95 percent CI 0.54-0.87; p=0.0016).
- IRC-assessed PFS was consistent with investigator-assessed PFS. As assessed by IRC, Gazyva-based
treatment reduced the risk of disease worsening or death by 28 percent compared to Rituxan-based treatment (HR=0.72; 95 percent
CI 0.56-0.93; p=0.0018). Median PFS has not yet been reached in either treatment arm.
- The most common Grade 3-5 AEs that occurred more often in the Gazyva arm compared to the Rituxan arm
were low white blood cell count (neutropenia, 46.7 percent vs. 39.5 percent), infections (20.3 percent vs. 16.4 percent),
infusion-related reactions (IRRs, 12.4 percent vs. 6.7 percent), low platelet count (thrombocytopenia, 6.1 percent vs. 2.7
percent), new tumors (second malignancies, 4.7 percent vs. 2.7 percent) and cardiac events (3.9 percent vs. 2.8 percent).
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.
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 2017.
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) injection, for intravenous use, 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.
Other side effects with Rituxan include:
- aching joints during or within hours of receiving an infusion
- more frequent upper respiratory tract infection
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.
Please see the Rituxan full Prescribing Information, including BOXED WARNINGS and the Medication Guide, for additional
Important Safety Information at http://www.Rituxan.com .
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.
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. For more information visit http://www.gene.com/hematology.
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 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.
Genentech
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Stephanie Huang, 650-467-6800
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Neera Dahiya Ravindran, M.D., 650-491-5281
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