Genentech Announces Submission of Supplemental New Drug Application for Venclexta for People With Previously Untreated Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY),
today announced submission of a supplemental New Drug Application (sNDA)
to the U.S. Food and Drug Administration (FDA) for Venclexta®
(venetoclax), in combination with a hypomethylating agent or in
combination with low dose cytarabine (LDAC), for treatment of people
with previously untreated acute myeloid leukemia (AML) who are
ineligible for intensive chemotherapy. The submission is based on the
results of two Phase Ib/II studies that evaluated Venclexta in
combination with azacitidine or decitabine (M14-358 study) or LDAC
(M14-387 study) in this patient population. Venclexta is being developed
by AbbVie and Genentech, a member of the Roche Group. It is jointly
commercialized by the companies in the U.S. and commercialized by AbbVie
outside of the U.S.

“Nearly 20,000 people will be diagnosed with AML in the U.S. this year,
and many of them are not eligible to receive standard intensive
chemotherapy,” said Sandra Horning, M.D., chief medical officer and head
of Global Product Development. “AML is an aggressive disease with the
lowest survival rate of all leukemias, and we look forward to working
closely with the FDA to bring this potential option to patients with
this very difficult-to-treat blood cancer as soon as possible.”

Data recently presented from the Phase Ib M14-358 study showed Venclexta
in combination with azacitidine or decitabine resulted in a complete
remission rate (with or without full recovery of normal blood cell
count; CR/CRi) of 73 percent in patients treated with Venclexta at a
dose of 400 mg. After more than a year of follow-up, the observed median
overall survival (OS) across all Venclexta dose groups in the study was
17.5 months (95 percent CI: 12.3-not reached). The most common Grade 3-4
adverse events (occurring in 10 percent or more patients) were low white
blood cell count with fever, low white blood cell count, anemia, low
platelet count and decreased potassium levels.

Additionally, results from the Phase Ib/II M14-387 study of Venclexta in
combination with LDAC showed a CR/CRi rate of 62 percent in patients
treated with Venclexta at a dose of 600 mg. After more than a year of
follow-up, the observed median OS was 11.4 months (95 percent CI:
5.7-15.7). The most common Grade 3-4 adverse events (occurring in 10
percent or more patients) were low white blood cell count with fever,
decreased potassium levels, pneumonia, disease progression, decreased
phosphate levels, high blood pressure and sepsis (blood infection).

The FDA previously granted two breakthrough therapy designations for
Venclexta in previously untreated AML ineligible for intensive
chemotherapy, either in combination with hypomethylating agents or LDAC,
based on results from these two studies. Recently, the FDA approved
Venclexta in combination with Rituxan® (rituximab) for the
treatment of people with chronic lymphocytic leukemia (CLL) or small
lymphocytic lymphoma (SLL), with or without 17p deletion, who have
received at least one prior therapy. A robust clinical development
program is ongoing in several other cancer types.

About the M14-358 study

The M14-358 study (NCT02203773) is an open-label, Phase Ib dose
escalation and expansion study evaluating the safety and efficacy of
Venclexta in combination with hypomethylating agents, azacitidine or
decitabine, in 212 patients who are 60 years or older with previously
untreated AML unfit to receive intensive chemotherapy. Study endpoints
included CR/CRi, OS and safety.

About the M14-387 study

The M14-387 study (NCT02287233) is an open-label, Phase Ib/II dose
escalation and expansion study evaluating the safety and efficacy of
Venclexta in combination with LDAC in 94 patients who are 60 years or
older with previously untreated AML unfit to receive intensive
chemotherapy. Study endpoints included CR/CRi, objective response rate
(ORR), OS and safety.

About AML

Acute myeloid leukemia (AML) is the most common type of aggressive
leukemia in adults, which has the lowest survival rate for all types of
leukemia. In 2018, it is estimated there will be nearly 20,000 new cases
of AML diagnosed in the U.S.

About Venclexta

Venclexta is a small molecule designed to selectively bind and inhibit
the BCL-2 protein, which plays an important role in a process called
apoptosis (programmed cell death). Overexpression of the BCL-2 protein
in AML has been associated with resistance to certain therapies. It is
believed that blocking BCL-2 may restore the signaling system that tells
cells, including cancer cells, to self-destruct. Venclexta is being
developed by AbbVie and Genentech, a member of the Roche Group. It is
jointly commercialized by the companies in the U.S. and commercialized
by AbbVie outside of the U.S.

Together, the companies are committed to further research with
Venclexta, which is currently being evaluated in Phase III clinical
trials for several types of blood cancers. In the U.S., Venclexta has
been granted four Breakthrough Therapy Designations by the FDA: 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 AML ineligible for intensive
chemotherapy; and in combination with LDAC for people with untreated AML
ineligible for intensive chemotherapy.

Venclexta Indication

Venclexta is a prescription medicine used to treat people with chronic
lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or
without 17p deletion, who have received at least one prior treatment.

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. A patient’s doctor will do tests for
TLS. It is important for patients taking Venclexta to keep their
appointments for blood tests. Patients will receive other medicines
before starting and during treatment with Venclexta to help reduce the
risk of TLS. Patients may also need to receive intravenous (IV) fluids
into their vein. Patients taking Venclexta must 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 when taking 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 their first dose, on the day of their
first dose of Venclexta, and each time the dose is increased.

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

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

Patients should not drink grapefruit juice or 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:

The most common side effects of Venclexta when used in combination
with rituximab include low white blood cell count, diarrhea, upper
respiratory tract infection, cough, tiredness, and nausea.

The most common side effects of Venclexta when used alone include
low white blood cell count, diarrhea, nausea, upper respiratory tract
infection, low red blood cell count, tiredness, low platelet count,
muscle and joint pain, swelling of the arms, legs, hands, and feet, and
cough.

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 must
tell their doctor if they have any side effect that bothers them or that
does not go away.

Report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch.
Patients and caregivers may also report side effects to Genentech at
(888) 835-2555.

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

Rituxan Indications

Rituxan® (rituximab) injection, for intravenous use, is
indicated for the treatment of:

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

Important Safety Information:

Rituxan can cause serious side effects that can lead to death,
including:

What should patients tell their doctor before receiving Rituxan?

Before receiving Rituxan, patients should tell their doctor if they:

What are the possible side effects of Rituxan?

Rituxan can cause serious side effects, including:

The patient’s doctor will stop treatment with Rituxan if they have
severe, serious, or life-threatening side effects.

What are the most common side effects during treatment with Rituxan?

Other side effects include:

These are not all of the possible side effects with Rituxan.

Please see the Rituxan full Prescribing Information, including 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. 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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