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Pivotal Phase III CLL14 Results for Venclexta in Combination with Gazyva for Chronic Lymphocytic Leukemia Presented at ASCO 2019 and Published in the New England Journal of Medicine

June 4, 2019 Off By BusinessWire

– Venclexta plus Gazyva showed improvements across multiple efficacy
measures compared to Gazyva plus chlorambucil, including
progression-free survival and deep remissions as determined by minimal
residual disease measurement –

– This 12-month, fixed-duration, chemotherapy-free combination was
recently approved for previously untreated chronic lymphocytic leukemia
under the FDA’s Real-Time Oncology Review pilot program –

CHICAGO–(BUSINESS WIRE)–Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY),
today announced results from the pivotal Phase III CLL14 study in
previously untreated chronic lymphocytic leukemia (CLL) showing that
Venclexta^® (venetoclax) plus Gazyva^®
(obinutuzumab) met its primary endpoint of investigator-assessed
progression-free survival (PFS). The 12-month, fixed-duration,
chemotherapy-free combination reduced the risk of disease worsening or
death by 65 percent compared to Gazyva plus chlorambucil (PFS, as
assessed by investigator; HR=0.35; 95 percent CI 0.23-0.53; p<0.001),
when given to people with previously untreated CLL who have co-existing
medical conditions. The results were presented at the 2019 American
Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously
published in the New England Journal of Medicine (NEJM).

At two years, one year after stopping treatment, nearly nine out of ten
patients (88.2 percent) in the Venclexta plus Gazyva arm remained
progression-free, compared to 64.1 percent in the Gazyva plus
chlorambucil arm. Safety for Venclexta plus Gazyva appeared consistent
with the known safety profiles of the individual medicines. Common Grade
3-4 adverse events with Venclexta plus Gazyva compared to Gazyva plus
chlorambucil, respectively, were low white blood cell count (52.8
percent vs. 48.1 percent) and infections (17.5 percent vs. 15.0 percent).

“The results of our Phase III CLL14 trial, reported today at ASCO and in
the New England Journal of Medicine, represent a major advance in
improving outcomes in chronic lymphocytic leukemia,” said Sandra
Horning, M.D., chief medical officer and head of Global Product
Development. “We are pleased this fixed-duration, chemotherapy-free
regimen of Venclexta plus Gazyva was approved by the FDA and look
forward to providing an important treatment option to even more adults
with the most common form of adult leukemia.”

The treatment benefit demonstrated with the Venclexta plus Gazyva
combination compared to Gazyva plus chlorambucil was consistent across
secondary endpoints, including:

Overall response (84.7 percent vs. 71.3 percent; p<0.001)
Complete response with at least partial blood count recovery (49.5
percent vs. 23.1 percent; p<0.001)
Minimal residual disease (MRD)-negativity in the bone marrow (56.9
percent vs. 17.1 percent; p<0.001) and peripheral blood (75.5 percent
vs. 35.2 percent; p<0.001) three months after treatment.
MRD-negativity means no cancer can be detected using a specific,
highly sensitive test, and was defined as less than one CLL cell in
10,000 white blood cells.

These data were presented at the 2019 ASCO Annual Meeting on Tuesday,
June 4, 2019, at 10:09-10:21 CST (Abstract #7502), and simultaneously
published in NEJM.

The U.S. Food and Drug Administration (FDA) approved the combination on
May 15, 2019, under the FDA’s Real-Time Oncology Review and Assessment
Aid pilot programs, for the treatment of people with previously
untreated CLL or small lymphocytic lymphoma. 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. Additional
submissions of the CLL14 data to health authorities around the world are
ongoing.

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.
Co-existing medical conditions included reduced kidney function or
co-morbidities assessed by a standard scale (Cumulative Illness Rating
Scale). 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
alongside 12-month duration of chlorambucil (Arm B). Arm A started with
an initial dosing of Gazyva followed by a five-week Venclexta dose
ramp-up to help reduce the risk of tumor lysis syndrome. 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
rate (ORR), complete response (with or without complete blood count
recovery), overall survival, duration of response, event-free survival,
time to next CLL treatment, and safety. The CLL14 study is being
conducted in cooperation with the German CLL Study Group, headed by
Michael Hallek, M.D., University of Cologne.

After a median follow-up of 28 months, results showed:

Patients who received Venclexta plus Gazyva lived significantly longer
without their disease worsening (PFS, as assessed by investigator)
compared to those who received Gazyva plus chlorambucil (HR 0.35; 95
percent CI 0.23-0.53; p<0.001).
- At two years, 88.2 percent of patients in the Venclexta plus
  Gazyva arm had not experienced disease progression, compared to
  64.1 percent with Gazyva plus chlorambucil.
- Median PFS reported by investigators was not yet reached in either
  arm. IRC assessment of PFS was consistent (HR 0.33; 95 percent CI,
  0.22-0.51; p<0.001).
Clinical benefit observed for Venclexta plus Gazyva compared to Gazyva
plus chlorambucil was consistent across secondary endpoints, including
ORR (84.7 percent vs. 71.3 percent; p<0.001) and CR including
incomplete marrow recovery (49.5 percent vs. 23.1 percent; p<0.001).
In addition, higher rates of MRD-negativity in the bone marrow (56.9
percent vs. 17.1 percent; p<0.001) and peripheral blood (75.5 percent
vs. 35.2 percent; p<0.001) were observed three months after treatment
with Venclexta plus Gazyva compared to Gazyva plus chlorambucil.
MRD-negativity was defined as less than one CLL cell in 10,000
leukocytes.
Safety for Venclexta plus Gazyva appeared consistent with the known
safety profile of the individual medicines, and no new safety signals
were identified with the combination. Common Grade 3-4 adverse events
with Venclexta plus Gazyva compared to Gazyva plus chlorambucil,
respectively, were low white blood cell count (52.8 percent vs. 48.1
percent) and infections (17.5 percent vs. 15.0 percent).

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 percent) or marginal zone
lymphoma (14 percent).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.

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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