Genentech Announces FDA Approval for Venclexta Plus Gazyva for People With Previously Untreated Chronic Lymphocytic Leukemia

– Fixed 12-month treatment with Venclexta plus Gazyva significantly
reduced risk of disease progression or death by 67 percent compared to a
current standard of care –

– Approval for expanded use of Venclexta offers more adults with
chronic lymphocytic leukemia a new treatment option –

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY),
today announced that the U.S. Food and Drug Administration (FDA) has
approved Venclexta® (venetoclax) in combination with Gazyva®
(obinutuzumab) for the treatment of people with previously
untreated chronic lymphocytic leukemia (CLL) or small lymphocytic
lymphoma (SLL).

“Venclexta plus Gazyva is the only chemotherapy-free option of fixed
duration that provides durable responses to help people live longer
without progression of their disease, compared to a standard of care,”
said Sandra Horning, M.D., chief medical officer and head of Global
Product Development. “Today’s approval represents our long-standing
commitment to helping people with blood cancers throughout the course of
their disease, and we are excited to provide this new option for
untreated chronic lymphocytic leukemia.”

The approval is based on the results of the randomized Phase III CLL14
study, which evaluated 12-month, fixed-duration treatment with Venclexta
plus Gazyva compared to Gazyva plus chlorambucil. Results showed the
combination of Venclexta plus Gazyva produced a durable and significant
reduction in the risk of disease worsening or death (progression-free
survival (PFS), as assessed by Independent Review Committee) by 67
percent compared to Gazyva plus chlorambucil, a current standard of care
(HR=0.33; 95 percent CI 0.22-0.51; p<0.0001). Venclexta plus Gazyva showed deep and clinically meaningful responses characterized by a higher rate of minimal residual disease (MRD)-negativity in the bone marrow compared to Gazyva plus chlorambucil (MRD-negativity of 57 percent vs. 17 percent) and peripheral blood (MRD-negativity of 76 percent vs. 35 percent). MRD-negativity means no cancer can be detected using a specific and highly sensitive test, defined as less than one CLL cell in 10,000 white blood cells.

Results of the study will be presented at the American Society of
Clinical Oncology Annual Meeting in June 2019. The CLL14 study is being
conducted in cooperation with the German CLL Study Group (GCLLSG),
headed by Michael Hallek, M.D., University of Cologne.

The most common adverse reactions with Venclexta plus Gazyva were low
white blood cell count, diarrhea, fatigue, nausea, low red blood cell
count, and upper respiratory tract infection.

The FDA rapidly reviewed and approved the supplemental New Drug
Application (sNDA) under the FDA’s Real-Time Oncology Review (RTOR) and
Assessment Aid pilot programs. This is the second regimen of Genentech
medicines approved under the RTOR pilot program, which is exploring a
more efficient review process to ensure safe and effective treatments
are available to patients as early as possible. The sNDA was also
granted Priority Review, a designation given 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 FDA
previously granted Breakthrough Therapy Designation for Venclexta in
combination with Gazyva for the treatment of previously untreated CLL
with co-existing medical conditions. Additional submissions of the CLL14
data to health authorities around the world are ongoing.

Venclexta is being developed by AbbVie and Genentech, a member of the
Roche Group. It is jointly commercialized by the companies in the United
States and commercialized by AbbVie outside of the United States.

The combination of Venclexta and Gazyva is taken for a fixed duration
unlike some other cancer medicines that are taken until disease
progression. For those who qualify, Genentech offers patient assistance
programs for people prescribed Venclexta and Gazyva by their doctor
through Genentech Access Solutions. Please contact Genentech Access
Solutions at (866) 422-2377 or visit http://www.Genentech-Access.com
for more information.

About the CLL14 Study

CLL14 (NCT02242942) is a randomized Phase III study evaluating the
combination of fixed-duration Venclexta plus Gazyva compared to Gazyva
plus chlorambucil in patients with previously untreated chronic
lymphocytic leukemia (CLL) and co-existing medical conditions. 432
patients with previously untreated CLL were randomly assigned to receive
either a 12-month duration of Venclexta alongside six-month duration of
Gazyva (Arm A) or six-month duration of Gazyva plus chlorambucil
followed by an additional six-month duration of chlorambucil (Arm B).
Arm A started with an initial cycle of Gazyva followed by a five-week
Venclexta dose ramp-up to help reduce tumor burden. The primary endpoint
of the study is investigator-assessed progression-free survival (PFS).
Secondary endpoints include PFS assessed by Independent Review Committee
(IRC), minimal residual disease (MRD) status, overall response (OR),
complete response (with or without complete blood count recovery,
CR/CRi), overall survival (OS), duration of response (DOR), event-free
survival (EFS), time to next CLL treatment (TTNT), and safety. The CLL14
study is being conducted in cooperation with the German CLL Study Group
(GCLLSG), headed by Michael Hallek, M.D., University of Cologne.

 

CLL14 Study Results

Treatment arm  

Venclexta + Gazyva
(n=216)

 

Gazyva +
chlorambucil
(n=216)

Progression Free Survival (PFS)a
Median PFS  

Independent Review
Committee (IRC): Not reached

  IRC: Not reached
Number of Events, n (%)   29 (13)   79 (37)
Hazard Ratio   IRC: HR = 0.33 (95% CI 0.22-0.51), p<0.0001
Response Rates
ORR % (95% CI)   85 (79-89)   71 (65-77)
p value   0.0007
CR/CRi %   50   23
p value   <0.0001
Minimal Residual Disease (MRD)b

MRD-negative %, bone
marrow (95% CI)

  57 (50-64)   17 (12-23)
p value   <0.0001

MRD-negative %,
peripheral blood (95% CI)

  76 (69-81)   35 (29-42)
p value   <0.0001
Overall Survival (OS)
OS   Not reached   Not reached

aApproval based on secondary endpoint of PFS
evaluated by IRC; data at median follow-up of 28 months

b Data at 3-months following end of
combination treatment

   

The most common adverse reactions with Venclexta plus Gazyva were low
white blood cell count, diarrhea, fatigue, nausea, low red blood cell
count, and upper respiratory tract infection.

About CLL/SLL

Chronic lymphocytic leukemia (CLL) is the most common type of adult
leukemia. In the United States, it is estimated that more than 20,000
new cases of CLL will be diagnosed in 2019. Although signs of CLL may
disappear for a period of time after initial treatment, the disease is
considered incurable and many people will require additional treatment
due to the return of cancerous cells.

In CLL, the cancer primarily occurs in the blood and bone marrow. Small
lymphocytic lymphoma (SLL) is similar to CLL, but primarily occurs in
the lymph nodes.

About Venclexta

Venclexta is a first-in-class targeted medicine designed to selectively
bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood
cancers and other tumors, BCL-2 builds up and prevents cancer cells from
dying or self-destructing, a process called apoptosis. Venclexta blocks
the BCL-2 protein and works to restore the process of apoptosis.

Venclexta is being developed by AbbVie and Genentech, a member of the
Roche Group. It is jointly commercialized by the companies in the United
States and commercialized by AbbVie outside of the United States.
Together, the companies are committed to research with Venclexta, which
is currently being studied in clinical trials across several types of
blood and other cancers.

In the United States, Venclexta has been granted five Breakthrough
Therapy Designations by the U.S. Food and Drug Administration (FDA): one
for previously untreated CLL, two for relapsed or refractory CLL and two
for previously untreated acute myeloid leukemia.

About Gazyva

Gazyva is an engineered monoclonal antibody designed to attach to CD20,
a protein found only on certain types of B-cells. Gazyva is designed to
attack and destroy targeted B-cells both directly and together with the
body’s immune system. Gazyva was discovered by Roche Innovation Center
Zurich, formerly 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.

Additional combination studies investigating Gazyva with other approved
or investigational medicines, including cancer immunotherapies and small
molecule inhibitors, are underway across a range of blood cancers.

Venclexta Indications

Venclexta is a prescription medicine used:

  • To treat adults with chronic lymphocytic leukemia (CLL) or small
    lymphocytic lymphoma (SLL).
  • In combination with azacitidine, or decitabine, or low-dose cytarabine
    to treat adults with newly-diagnosed acute myeloid leukemia (AML) who:

    Are 75 years of age or older, or
    ‒ Have other medical
    conditions that prevent the use of standard chemotherapy.

It is not known if Venclexta is safe and effective in children.

Important Safety Information

Venclexta can cause serious side effects, including:

Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown
of cancer cells. TLS can cause kidney failure, the need for dialysis
treatment, and may lead to death. The patient’s doctor will do tests to
check their risk of getting TLS before they start taking Venclexta. The
patient will receive other medicines before starting and during
treatment with Venclexta to help reduce the risk of TLS. The patient may
also need to receive intravenous (IV) fluids through their vein.

The patient’s doctor will do blood tests to check for TLS when the
patient first starts treatment and during treatment with Venclexta. It
is important for patients to keep appointments for blood tests. Patients
should tell their doctor right away if they have any symptoms of TLS
during treatment with Venclexta, including fever, chills, nausea,
vomiting, confusion, shortness of breath, seizures, irregular heartbeat,
dark or cloudy urine, unusual tiredness, or muscle or joint pain.

Patients should drink plenty of water during treatment with Venclexta
to help reduce the risk of getting TLS.

Patients should drink 6 to 8 glasses (about 56 ounces total) of water
each day, starting 2 days before the first dose, on the day of the first
dose of Venclexta, and each time a dose is increased.

The patient’s doctor may delay, decrease the dose, or stop treatment
with Venclexta if the patient has side effects.

Certain medicines must not be taken when the patient first starts
taking Venclexta and while the dose is being slowly increased because of
the risk of increased tumor lysis syndrome.

  • Patients must tell their doctor about all the medicines they take, including
    prescription and over-the-counter medicines, vitamins, and herbal
    supplements. Venclexta and other medicines may affect each other,
    causing serious side effects.
  • Patients must not start new medicines during treatment with Venclexta
    without first talking with their doctor.

Before taking Venclexta, patients must tell their doctor about
all of their medical conditions, including if they:

  • Have kidney problems.
  • Have problems with body salts or electrolytes, such as potassium,
    phosphorus, or calcium.
  • Have a history of high uric acid levels in the blood or gout.
  • Are scheduled to receive a vaccine. The patient should not receive a
    “live vaccine” before, during, or after treatment with Venclexta,
    until the patient’s doctor tells them it is okay. If the patient is
    not sure about the type of immunization or vaccine, the patient should
    ask their doctor. These vaccines may not be safe or may not work as
    well during treatment with Venclexta.
  • Are pregnant or plan to become pregnant. Venclexta may harm an unborn
    baby. If the patient is able to become pregnant, the patient’s doctor
    should do a pregnancy test before the patient starts treatment with
    Venclexta, and the patient should use effective birth control during
    treatment and for at least 30 days after the last dose of Venclexta.
    If the patient becomes pregnant or thinks they are pregnant, the
    patient should tell their doctor right away.
  • Are breastfeeding or plan to breastfeed. It is not known if Venclexta
    passes into the patient’s breast milk. Patients should not breastfeed
    during treatment with Venclexta.

What to avoid while taking Venclexta:

Patients should not drink grapefruit juice, eat grapefruit, Seville
oranges (often used in marmalades), or starfruit while they are taking
Venclexta. These products may increase the amount of Venclexta in the
patient’s blood.

Venclexta can cause serious side effects, including:

  • Low white blood cell counts (neutropenia). Low white blood cell
    counts are common with Venclexta, but can also be severe. The
    patient’s doctor will do blood tests to check their blood counts
    during treatment with Venclexta.
  • Infections. Death and serious infections such as pneumonia and
    blood infection (sepsis) have happened during treatment with
    Venclexta. The patient’s doctor will closely monitor and treat the
    patient right away if they have a fever or any signs of infection
    during treatment with Venclexta. Patients should tell their doctor
    right away if they have a fever or any signs of an infection during
    treatment with Venclexta.

The most common side effects of Venclexta when used in combination
with obinutuzumab or rituximab or alone in people with CLL or SLL
include
low white blood cell counts; low platelet counts; low red
blood cell counts; diarrhea; nausea; upper respiratory tract infection;
cough; muscle and joint pain; tiredness; and swelling of your arms,
legs, hands, and feet.

The most common side effects of Venclexta in combination with
azacitidine, or decitabine, or low-dose cytarabine in people with AML
include
low white blood cell counts; nausea; diarrhea; low platelet
counts; constipation; fever with low white blood cell counts; low red
blood cell counts; infection in blood; rash; dizziness; low blood
pressure; fever; swelling of arms, legs, hands, and feet; vomiting;
tiredness; shortness of breath; bleeding; infection in lung; stomach
(abdominal) pain; pain in muscles or back; cough; and sore throat.

Venclexta may cause fertility problems in males. This may affect the
ability to father a child. Patients should talk to their doctor if they
have concerns about fertility.

These are not all the possible side effects of Venclexta. Patients
should tell their doctor about any side effect that bothers them or that
does not go away.

Report side effects to the FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch.
Report side effects to Genentech at 1-888-835-2555.

Please visit http://www.Venclexta.com
for the Venclexta full Prescribing Information, including Patient
Information, for additional Important Safety Information.

Gazyva 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.
  • With chemotherapy, followed by Gazyva alone in those who responded, to
    treat stage II bulky, III, or IV FL in adults who have not had
    previous FL treatment.

Important Safety Information

The most important safety information patients should know about
Gazyva

Patients must tell their doctor right away about any side effect 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 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. Symptoms 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.

Additional possible serious side effects of Gazyva:

Patients must tell their doctor right away about any side effect 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 the patient has a reaction,
    the infusion is either slowed or stopped until their 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. 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. 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
    patients 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, the patient’s 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. 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 the patient is taking Gazyva, they may
    develop infections. Some of these infections may be fatal and severe,
    so the patient should be sure to talk to their doctor if they think
    they 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 the patient has an abnormally
    low count of infection-fighting white blood cells, it is called
    neutropenia. While the patient is taking Gazyva, their doctor will do
    blood work to check their 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 the patient’s white blood cell count is low, their 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 their
    blood; having low platelet count is called thrombocytopenia. This may
    affect the clotting process. While the patient is taking Gazyva, their
    doctor will do blood work to check their platelet count. Severe and
    life-threatening thrombocytopenia can develop during treatment with
    Gazyva. Fatal bleeding events have occurred in patients treated with
    Gazyva. If the patient’s platelet count gets too low, their 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 percent), 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.

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

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

Patients should 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/

Contacts

Media Contact:
Priscilla White, (650) 467-6800

Advocacy Contact:
Eydith Comenencia Ortiz, (650) 745-5210

Investor Contacts:
Loren Kalm, (650) 225-3217
Karl Mahler, +41
61 687 85 03

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