Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY),
today announced that the U.S. Food and Drug Administration (FDA)
approved a supplemental biologics license application (sBLA) for Gazyva
in combination with chlorambucil chemotherapy in people with previously
untreated chronic lymphocytic leukemia (CLL). The sBLA adds to the label
data from Stage 2 of the CLL11 study showing significant improvements
with Gazyva plus chlorambucil across multiple clinical endpoints when compared
head-to-head with Rituxan® (rituximab) plus
chlorambucil.
The approval includes complete response (CR) and minimal residual
disease (MRD) data from Stage 2 of the study. Additionally, overall
survival (OS) data was added from Stage 1 of the study comparing Gazyva
plus chlorambucil to chlorambucil alone.
“Gazyva is the first and only medicine to significantly help people live
without their disease worsening when combined with chlorambucil compared
to Rituxan and chlorambucil in people with previously untreated chronic
lymphocytic leukemia,” said Sandra Horning, M.D., chief medical officer
and head of Global Product Development. “These new data enhance our
understanding of the disease and its treatment, and this approval
affirms an important treatment option for people with this
difficult-to-treat disease.”
The sBLA approval updated the Gazyva prescribing information with the
following data:
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Gazyva plus chlorambucil helped people with previously untreated CLL
live nearly a year longer without their disease worsening or death
(progression-free survival; PFS) than Rituxan plus chlorambucil
(median PFS: 26.7 months vs. 14.9 months, respectively. HR=0.42, 95
percent CI 0.33-0.54, p<0.0001).
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Gazyva plus chlorambucil nearly tripled the number of people showing
no evidence of disease (CR) compared to Rituxan plus chlorambucil
(26.1 percent vs. 8.8 percent, respectively).
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Of the people who achieved a complete response with or without
complete recovery from abnormal blood cell counts (CR, CRi), 19
percent (18/94) of people in the Gazyva arm compared to 6 percent
(2/34) of people in the Rituxan arm were MRD negative in the bone
marrow, and 41 percent (39/94) of people in the Gazyva arm compared to
12 percent (4/34) people in the Rituxan arm were MRD negative in the
peripheral blood. MRD negative means no residual traces of the cancer
were found.
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Data from the first stage of the CLL11 study showed that at nearly two
years, the rate of death was 9 percent (22/238) for people who
received Gazyva plus chlorambucil compared to 20 percent (24/118) for
those who received chlorambucil alone (HR=0.41, 95 percent CI
0.23-0.74). The median OS has not yet been reached.
Gazyva can cause serious or life-threatening side effects including:
Hepatitis B reactivation, progressive multifocal leukoencephalopathy
(PML), infusion reactions, tumor lysis syndrome, infections, and low
white blood cell counts. The most common side effects of Gazyva are
infusion reactions, low white blood cell counts, low platelet counts,
low red blood cell counts, fever, cough, nausea, and diarrhea.
Gazyva, the first medicine approved with the FDA’s Breakthrough Therapy
Designation, was approved for use in combination with chlorambucil in
people with previously untreated CLL on November 1, 2013. Gazyva, known
as Gazyvaro in Europe, was approved by the European Commission for the
same indication in July 2014. Gazyva is also being investigated in a
broad development program across various types of blood cancers,
including multiple Phase III studies in non-Hodgkin’s lymphoma (NHL).
About the CLL11 Study
CLL11 is a Phase III, multicenter, open-label, randomized three-arm
study, conducted in cooperation with the German CLL Study Group, in 781
previously untreated people with CLL and co-existing medical conditions.
Stage 1 (n=589) compared Gazyva plus chlorambucil to chlorambucil alone
and Rituxan plus chlorambucil to chlorambucil alone. Stage 2 (n=663)
compared Gazyva plus chlorambucil directly with Rituxan plus
chlorambucil. The primary endpoint of the study was PFS with secondary
endpoints including overall response rate (ORR), OS, CR, median duration
of response, MRD and safety profile. Results from Stage 2 and updated
data from Stage 1 were presented in 2013 during the Plenary Scientific
Session of the American Society of Hematology (ASH) meeting and
published in the New England Journal of Medicine in 2014.
About Chronic Lymphocytic Leukemia (CLL)
CLL is one of the most common forms of blood cancer and in 2014, it is
expected that there will be nearly 5,000 deaths from CLL in the United
States. Most cases of CLL (95 percent) start in white blood cells called
B-cells that have a protein called CD20 on their surface.
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 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 is thought to have an
increased ability to induce direct cell death and induces greater
activity in how it recruits the body’s immune system to attack B-cells
(antibody dependent cellular cytotoxicity; ADCC) when compared to
Rituxan. 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 Idec.
Gazyva Indication
Gazyva is a prescription medicine used with the chemotherapy
chlorambucil, to treat chronic lymphocytic leukemia (CLL) in adults who
have not had previous CLL 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 a few 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: dizziness, nausea, chills, fever, vomiting,
diarrhea, breathing problems, and chest pain
-
Tumor Lysis Syndrome (TLS): 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
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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. 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
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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.
Neutropenia can develop during or after treatment with Gazyva. It may
also 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
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Low Platelet Count: Platelets help stop bleeding or blood loss.
Gazyva may reduce the number of platelets the patient has in the
blood. 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
Most common side effects of Gazyva
The most common side effects of Gazyva are infusion reactions, low white
blood cell counts, low platelet counts, low red blood cell counts,
fever, cough, nausea, and diarrhea.
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. It is not known
if Gazyva may harm the patient’s unborn baby or pass into the patient’s
breast milk. The patient should use birth control while using Gazyva and
for 12 months after treatment. 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.
The patient should speak to the doctor about discontinuing Gazyva if the
patient is breastfeeding.
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 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 full Prescribing Information, including Boxed WARNINGS, for
additional Important Safety Information.
Rituxan Indications
Rituxan (rituximab) is indicated for the treatment of patients with:
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Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell
NHL as a single agent
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Previously untreated follicular, CD20-positive, B-cell NHL in
combination with first-line chemotherapy and, in patients achieving a
complete or partial response to Rituxan in combination with
chemotherapy, as single-agent maintenance therapy
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Non-progressing (including stable disease), low-grade, CD20-positive,
B-cell NHL, as a single agent, after first-line CVP chemotherapy
-
Previously untreated diffuse large B-cell, CD20-positive NHL in
combination with CHOP or other anthracycline-based chemotherapy
regimens
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Previously untreated and previously treated CD20-positive CLL in
combination with fludarabine and cyclophosphamide (FC)
Rituxan is not recommended for use in patients with severe,
active infections.
Important Safety Information:
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. Patient 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 see the Rituxan full Prescribing Information, including Most
Serious Side Effects, for additional important safety information at http://www.Rituxan.com.
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 cancers of the blood. Genentech’s pipeline of potential hematology
medicines includes an antibody-drug conjugate (anti-CD79b; polatuzumab
vedotin), a small molecule antagonist of MDM2 (RG7388) and in
collaboration with AbbVie, a small molecule BCL-2 inhibitor
(GDC-0199/ABT-199; venetoclax).
About Genentech
Founded more than 35 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.
Copyright Business Wire 2014