Genentech Submits Supplemental New Drug Application to FDA for Venclexta Plus Gazyva for Previously Untreated Chronic Lymphocytic Leukemia with Co-Existing Medical Conditions

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY),
today announced the submission of a supplemental New Drug Application to
the U.S. Food and Drug Administration (FDA) for Venclexta^®
(venetoclax) in combination with Gazyva^® (obinutuzumab) in
people with previously untreated chronic lymphocytic leukemia (CLL) and
co-existing medical conditions. The FDA is reviewing the application
under the Real-Time Oncology Review pilot program, which aims to explore
a more efficient review process to ensure safe and effective treatments
are available to patients as early as possible.

“More than 20,000 people will be diagnosed with untreated chronic
lymphocytic leukemia in the United States this year, and many are
ineligible for intensive chemotherapy-based options,” said Sandra
Horning, M.D., chief medical officer and head of Global Product
Development. “We are encouraged that this chemotherapy-free,
fixed-duration combination is being reviewed under the FDA’s Real-Time
Oncology Review pilot program, and we are working closely with the
agency to bring this new option to people with previously untreated
chronic lymphocytic leukemia as quickly as possible.”

Breakthrough Therapy Designation was granted based on results of the
randomized Phase III CLL14 study, evaluating the fixed-duration
combination of Venclexta plus Gazyva, compared to Gazyva plus
chlorambucil, in people with previously untreated CLL and co-existing
medical conditions. The study met its primary endpoint and showed a
statistically significant reduction in the risk of disease worsening or
death (progression-free survival [PFS] as assessed by investigator)
compared to standard-of-care Gazyva plus chlorambucil. Safety for the
Venclexta plus Gazyva combination appeared consistent with the known
safety profiles of the individual medicines, and no new safety signals
were identified with the combination. Data from the CLL14 study will be
presented at an upcoming medical meeting. The CLL14 study is being
conducted in cooperation with the German CLL Study Group (GCLLSG),
headed by Michael Hallek, M.D., University of Cologne.

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.

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).
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, event-free survival, time to next CLL treatment 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.

About CLL

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.

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): in
combination with Gazyva for people with previously untreated chronic
lymphocytic leukaemia (CLL) and co-existing medical conditions; in
combination with Rituxan for people with relapsed or refractory CLL; as
a monotherapy for people with relapsed or refractory CLL with 17p
deletion; in combination with hypomethylating agents (azacitidine or
decitabine) for people with untreated acute myeloid leukemia (AML)
ineligible for intensive chemotherapy; and in combination with low-dose
cytarabine for people with untreated AML ineligible for intensive
chemotherapy.

About Gazyva

Gazyva is an engineered monoclonal antibody designed to attach to CD20,
a protein found only 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 underway across a range of blood cancers.

Venclexta Indications

Venclextais a prescription medicine used:

• To treat adults with chronic lymphocytic leukemia (CLL) or small
  lymphocytic lymphoma (SLL), with or without 17p deletion, who have
  received at least 1 prior treatment.
• 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. 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 rituximab in people with CLL include low white blood cell
counts; diarrhea; upper respiratory tract infection; cough; tiredness;
and nausea.

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

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/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.

About the German CLL Study Group (GCLLSG)

Founded in 1996 and headed by Michael Hallek, M.D., the GCLLSG has been
running various Phase III, Phase II and Phase I trials in chronic
lymphocytic leukemia (CLL) with the goal to provide optimal treatment to
patients suffering from this disease. Among those were landmark trials
like the CLL8 and the CLL11 trials which led to the current standard of
care in CLL. For many years, GCLLSG has been aiming to improve not just
the treatment of younger and physically fit patients, but also that of
elderly and less fit patients. These patients are generally
underrepresented in clinical trials although they constitute the
majority of CLL patients treated by doctors in daily practice. The
GCLLSG is an independent non-profit research organization supported by
the German Cancer Aid (Deutsche Krebshilfe). http://www.dcllsg.de.

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. 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 and 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.

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