NORTH CHICAGO, Ill.,
Oct. 16, 2020 /PRNewswire/ -- AbbVie
(NYSE: ABBV) today announced that the U.S. Food and Drug
Administration (FDA) has provided full approval to VENCLEXTA®
(venetoclax) in combination with azacitidine, or
decitabine, or low-dose cytarabine (LDAC) for the treatment of
newly-diagnosed acute myeloid leukemia (AML) in adults who are age
75 years or older, or who have comorbidities that preclude the use
of intensive induction chemotherapy. The approval is supported
by data from the Phase 3 VIALE-A (M15-656) and
VIALE-C (M16-043) studies and updated data from the
Phase 1b M14-358 and the Phase 1/2
M14-387 studies. The FDA previously granted accelerated approval to
VENCLEXTA for this indication in 2018.5
"AML is a complex and challenging disease with generally low
survival rates. This approval is significant because data from our
VIALE-A trial has shown that newly-diagnosed patients, who cannot
undergo intensive chemotherapy, lived longer when treated with
VENCLEXTA plus azacitidine than those treated with azacitidine
alone," said Mohamed Zaki, M.D.,
Ph.D., vice president and global head of oncology development,
AbbVie. "This trial also provides physicians more information for
managing patients - from treatment initiation, to assessing
response and management post disease remission."
Positive overall survival (OS) data seen at an interim analysis
of the VIALE-A trial led to an early submission supporting the FDA
approval of VENCLEXTA in AML. The trial showed patients on the
active regimen of VENCLEXTA plus azacitidine achieved a 34%
reduction in the risk of death compared to azacitidine in
combination with placebo (Hazard Ratio [HR]=0.66 [95% CI:
0.52-0.85], p<0.001). The median OS for patients in the
VENCLEXTA arm was 14.7 months (95% CI: 11.9, 18.7) versus 9.6
months in the placebo arm (95% CI: 7.4, 12.7). Additionally,
patients in the VENCLEXTA plus azacitidine arm achieved a
complete remission (CR) rate of 37% (95% CI: 31%, 43%) with a
median duration of CR of 18.0 months (95% CI: 15.3, -) compared
with patients in the placebo plus azacitidine arm with a CR
rate of 18% (95% CI: 12%, 25%) with a median duration of CR of 13.4
months (95% CI: 8.7, 17.6). The observed safety profile was
generally consistent with the known safety profile of VENCLEXTA in
combination with azacitidine. For patients taking VENCLEXTA in
combination with azacitidine, the most frequent serious adverse
reactions (ARs; ≥5%) at first use were febrile neutropenia (30%),
pneumonia (22%), sepsis (excluding fungal; 19%) and hemorrhage
(6%).1,6
Data from VIALE-A was presented for the first time as a
late-breaking abstract at the 25th European Hematology
Association (EHA) Annual Congress in June
2020 and recently published in the New England Journal of
Medicine.7
"For far too long, people with AML had very few treatment
options, aside from very intense chemotherapy. Today's news
continues the progress of bringing more treatment options to
patients with this devastating disease," said Lee Greenberger, Ph.D., chief scientific officer
of The Leukemia & Lymphoma Society.
Data from the VIALE-C trial was presented at both the 2020
American Society of Clinical Oncology (ASCO) Annual Meeting and the
EHA Annual Congress and previously published in
Blood.8 The median OS for VENCLEXTA
in combination with LDAC was 7.2 months (95% CI: 5.6, 10.1) and 4.1
months for LDAC in combination with placebo (95% CI: 3.1, 8.8). The
HR for the primary endpoint of OS was 0.75 (95% CI: 0.52-1.07;
p=0.114). The trial did not meet its primary endpoint of
statistically significant improvement of OS for patients with AML
who are ineligible for intensive chemotherapy at the time of the
planned analysis. Efficacy was based on the rate of CR and duration
of CR with supportive evidence of rate of CR + complete remission
with partial hematologic recovery (CR+CRh), duration of CR+CRh, and
the rate of conversion from transfusion dependence to transfusion
independence. In the VENCLEXTA arm, the most frequent serious ARs
were (≥10%) pneumonia (17%), febrile neutropenia (16%) and sepsis
(excluding fungal; 12%).1,9
AML is an aggressive and difficult-to-treat blood cancer with a
low survival rate.2,3 Despite
recent advances in available therapies, the five-year survival rate
for patients diagnosed with AML remains approximately
29%.10 AML typically worsens quickly, and due to
age or comorbidities, not all patients are eligible to receive
intensive chemotherapy.11
The FDA reviewed the clinical data under the FDA's Real-Time
Oncology Review (RTOR) pilot program and Project Orbis initiative,
which led to approval in the U.S. in October
2020. Project Orbis provides a framework for concurrent
submission and review of oncology drugs among international
partners. The U.S. FDA, the Australian Therapeutic Goods
Administration, Swissmedic, Health Canada and ANVISA (Agência
Nacional de Vigilância Sanitária) collaborated on this review based
on the marketing applications submitted in their respective
countries.
Venetoclax is being developed by AbbVie and Roche. It is jointly
commercialized by AbbVie and Genentech, a member of the Roche
Group, in the U.S. and by AbbVie outside of the U.S.
About the VIALE-A and VIALE-C Clinical Trials
VIALE-A (M15-656) Phase 3
Trial1,7
A total of 431 patients were randomized in the double-blind,
placebo-controlled, multicenter, Phase 3 VIALE-A trial, which
evaluated the efficacy and safety of VENCLEXTA in combination with
azacitidine (n=286) in patients with AML who are ineligible for
standard induction therapy versus azacitidine in combination with
placebo (n=145). The primary endpoint was OS.
The VENCLEXTA plus azacitidine combination showed a median
OS of 14.7 months (95% CI: 11.9, 18.7) versus 9.6 months (95% CI:
7.4, 12.7) with azacitidine in combination with placebo. The study
also met its secondary endpoints, with the
VENCLEXTA combination arm resulting in a CR rate of 37% (95%
CI: 31, 43) and a CR+CRh rate of 65% (95% CI: 59, 70) compared to a
CR rate of 18% (95% CI: 12, 25) and a CR+CRh rate of 23% (95% CI:
16, 30) in the placebo arm. The median time to first response of CR
or CRh was 1.0 months (range: 0.6 to 14.3 months) with
VENCLEXTA in combination with azacitidine. The median duration
of treatment was 7.6 months (range: <0.1 to 30.7 months) in the
VENCLEXTA arm.
The most frequent ARs (≥30% with a difference between arms of
≥5%) for patients taking VENCLEXTA in combination with azacitidine
were mostly hematologic and gastrointestinal in nature and
consisted of, nausea (44%), diarrhea (43%), febrile neutropenia
(42%), musculoskeletal pain (36%), fatigue (31%), and vomiting
(30%). Serious adverse reactions were reported in 83% of patients
in the VENCLEXTA arm, with the most frequent serious ARs (≥5%)
being febrile neutropenia (30%), pneumonia (22%), sepsis (excluding
fungal; 19%) and hemorrhage (6%).
VIALE-C (M16-043) Phase 3
Trial1,9
A total of 211 patients were enrolled and treated in the
randomized, double-blind, placebo-controlled, multicenter, Phase 3
VIALE-C trial, which evaluated the efficacy and safety of VENCLEXTA
in combination with LDAC (n=143) versus placebo with LDAC (n=68).
The primary endpoint was OS.
VENCLEXTA in combination with LDAC did not significantly improve
OS versus placebo in combination with LDAC. The HR for OS was 0.75
(95% CI: 0.52, 1.07); p-value 0.114. The median OS for VENCLEXTA in
combination with LDAC arm was 7.2 months (95% CI: 5.6, 10.1) and
for PBO+LDAC arm was 4.1 months (95% CI: 3.1, 8.8).
Efficacy was based on the rate of CR and duration of CR with
supportive evidence of rate of CR+CRh, duration of CR+CRh, and the
rate of conversion from transfusion dependence to transfusion
independence. The CR rate in the VENCLEXTA in combination with LDAC
arm was 27% (95% CI: 20%, 35%) with a median duration of CR of 11.1
months (95% CI: 6.1, -), and the CR rate in the placebo arm was
7.4% (95% CI: 2.4%, 16%) with a median duration of CR of 8.3 months
(95% CI: 3.1, - ). The CR+CRh rate in the VENCLEXTA in combination
with LDAC arm was 47% (95% CI: 39%, 55%) and in the placebo arm was
15% (95% CI: 7.3%, 25%) with a median duration of CR+CRh of 11.1
months with VENCLEXTA in combination with LDAC and 6.2 months with
LDAC in combination with placebo. The median time to first response
of CR or CRh was 1.0 month (range: 0.7 to 5.8 months) with
VENCLEXTA in combination with LDAC.
The most frequent AR (≥30% with a difference between arms of
≥5%) for patients taking VENCLEXTA in combination with LDAC was
nausea (42%). Serious ARs were reported in 65% of patients in the
VENCLEXTA arm, with the most frequent (≥10%) being pneumonia
(17%), febrile neutropenia (16%), and sepsis (excluding fungal;
12%).
About VENCLEXTA® (venetoclax)
VENCLEXTA® (venetoclax) is a first-in-class medicine that
selectively binds and inhibits the B-cell lymphoma-2 (BCL-2)
protein. In some blood cancers, BCL-2 prevents cancer cells from
undergoing their natural death or self-destruction process, called
apoptosis. VENCLEXTA targets the BCL-2 protein and works to help
restore the process of apoptosis.
VENCLEXTA is being developed by AbbVie and Roche. It is jointly
commercialized by AbbVie and Genentech, a member of the Roche
Group, in the U.S. and by AbbVie outside of the U.S. Together, the
companies are committed to BCL-2 research and to studying
venetoclax in clinical trials across several blood and other
cancers. VENCLEXTA is approved in more than 50 countries, including
the U.S.
Uses and Important VENCLEXTA® (venetoclax) U.S. Safety
Information1
Uses
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
What is the most important information I should know about
VENCLEXTA?
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. Your healthcare
provider will do tests to check your risk of getting TLS before you
start taking VENCLEXTA. You will receive other medicines before
starting and during treatment with VENCLEXTA to help reduce your
risk of TLS. You may also need to receive intravenous (IV) fluids
into your vein. Your healthcare provider will do blood tests to
check for TLS when you first start treatment and during treatment
with VENCLEXTA. It is important to keep your appointments for blood
tests. Tell your healthcare provider right away if you 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.
Drink plenty of water during treatment with VENCLEXTA to help
reduce your risk of getting TLS. Drink 6 to 8 glasses
(about 56 ounces total) of water each day, starting 2 days before
your first dose, on the day of your first dose of VENCLEXTA, and
each time your dose is increased.
Your healthcare provider may delay, decrease your dose, or stop
treatment with VENCLEXTA if you have side effects.
Who should not take VENCLEXTA?
Certain medicines must not be taken when you first start
taking VENCLEXTA and while your dose is being slowly increased
because of the risk of increased TLS.
- Tell your healthcare provider about all the medicines you
take, including prescription and over-the- counter
medicines, vitamins, and herbal supplements. VENCLEXTA and other
medicines may affect each other causing serious side effects.
- Do not start new medicines during treatment with VENCLEXTA
without first talking with your healthcare provider.
Before taking VENCLEXTA, tell your healthcare provider about
all of your medical conditions, including if you:
- have kidney or liver problems.
- have problems with your body salts or electrolytes, such as
potassium, phosphorus, or calcium.
- have a history of high uric acid levels in your blood or
gout.
- are scheduled to receive a vaccine. You should not receive a
"live vaccine" before, during, or after treatment with VENCLEXTA,
until your healthcare provider tells you it is okay. If you are not
sure about the type of immunization or vaccine, ask your healthcare
provider. 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
your unborn baby. If you are able to become pregnant, your
healthcare provider should do a pregnancy test before you start
treatment with VENCLEXTA, and you should use effective birth
control during treatment and for at least 30 days after the last
dose of VENCLEXTA. If you become pregnant or think you are
pregnant, tell your healthcare provider right away.
- are breastfeeding or plan to breastfeed. It is not known if
VENCLEXTA passes into your breast milk. Do not breastfeed during
treatment and for 1 week after the last dose of
VENCLEXTA.
What should I avoid while taking VENCLEXTA?
You should not drink grapefruit juice or eat
grapefruit, Seville oranges (often used in marmalades),
or starfruit while you are taking VENCLEXTA. These products may
increase the amount of VENCLEXTA in your blood.
What are the possible side effects of VENCLEXTA?
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. Your healthcare provider will do blood tests to check your
blood counts during treatment with VENCLEXTA and may pause
dosing.
- Infections. Death and serious infections such as
pneumonia and blood infection (sepsis) have happened during
treatment with VENCLEXTA. Your healthcare provider will closely
monitor and treat you right away if you have a fever or any signs
of infection during treatment with VENCLEXTA.
Tell your healthcare provider right away if you 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 nausea, diarrhea, low platelet count, constipation, low
white blood cell count, fever with low white blood cell count,
tiredness, vomiting, swelling of arms, legs, hands, or feet, fever,
infection in lungs, shortness of breath, bleeding, low red blood
cell count, rash, stomach (abdominal) pain, infection in your
blood, muscle and joint pain, dizziness, cough, sore throat, and
low blood pressure.
VENCLEXTA may cause fertility problems in males. This may affect
your ability to father a child. Talk to your healthcare provider if
you have concerns about fertility.
These are not all the possible side effects of VENCLEXTA. Call
your doctor for medical advice about side effects.
You are encouraged to report negative side effects of
prescription drugs to the FDA. Visit www.fda.gov/medwatch or call
1-800-FDA-1088.
If you are having difficulty paying for your medicine, AbbVie
may be able to help. Visit AbbVie.com/myAbbVieAssist to learn
more.
The full U.S. prescribing information, including Medication
Guide, for VENCLEXTA can be
found here. Globally, prescribing
information varies; refer to the individual country product label
for complete information.
About AbbVie in Oncology
At AbbVie, we are committed
to transforming standards of care for multiple blood cancers while
advancing a dynamic pipeline of investigational therapies across a
range of cancer types. Our dedicated and experienced team joins
forces with innovative partners to accelerate the delivery of
potentially breakthrough medicines. We are evaluating more than 20
investigational medicines in over 300 clinical trials across some
of the world's most widespread and debilitating cancers. As we work
to have a remarkable impact on people's lives, we are committed to
exploring solutions to help patients obtain access to our cancer
medicines. For more information, please visit
http://www.abbvie.com/oncology.
About AbbVie
AbbVie's mission is to discover and
deliver innovative medicines that solve serious health issues today
and address the medical challenges of tomorrow. We strive to have a
remarkable impact on people's lives across several key therapeutic
areas: immunology, oncology, neuroscience, eye care, virology,
women's health and gastroenterology, in addition to products and
services across its Allergan Aesthetics portfolio. For more
information about AbbVie, please visit us at www.abbvie.com.
Follow @abbvie on Twitter, Facebook, Instagram, YouTube and LinkedIn.
Forward-Looking Statements
Some statements in this
news release are, or may be considered, forward-looking statements
for purposes of the Private Securities Litigation Reform Act of
1995. The words "believe," "expect," "anticipate," "project" and
similar expressions, among others, generally identify
forward-looking statements. AbbVie cautions that these
forward-looking statements are subject to risks and uncertainties
that may cause actual results to differ materially from those
indicated in the forward-looking statements. Such risks and
uncertainties include, but are not limited to, failure to realize
the expected benefits from AbbVie's acquisition of Allergan plc
("Allergan"), failure to promptly and effectively integrate
Allergan's businesses, competition from other products, challenges
to intellectual property, difficulties inherent in the research and
development process, adverse litigation or government action,
changes to laws and regulations applicable to our industry and the
impact of public health outbreaks, epidemics or pandemics, such as
COVID-19. Additional information about the economic, competitive,
governmental, technological and other factors that may affect
AbbVie's operations is set forth in Item 1A, "Risk Factors," of
AbbVie's 2019 Annual Report on Form 10-K, which has been filed with
the Securities and Exchange Commission, as updated by its
subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no
obligation to release publicly any revisions to forward-looking
statements as a result of subsequent events or developments, except
as required by law.
1 VENCLEXTA (venetoclax) [Package Insert]. North Chicago, IL.: AbbVie Inc.
2 Döhner H, et al. Acute myeloid leukemia. N Engl
J Med. 2015;373(12):1136-1152.
3 American Cancer Society (2019). Typical Treatment
of Most Types of Acute Myeloid Leukemia (Except Acute Promyelocytic
M3).
https://www.cancer.org/cancer/acute-myeloid-leukemia/treating/typical-treatment-of-aml.html.
Accessed October 2020.
4 Referenced with permission from the NCCN Clinical
Practice Guidelines in Oncology (NCCN Guidelines®) for Acute
Myeloid Leukemia V.1.2021. © National Comprehensive Cancer Network,
Inc. 2020. All rights reserved. Accessed October 16, 2020. To view the most recent and
complete version of the guideline, go online to NCCN.org. NCCN
makes no warranties of any kind whatsoever regarding their content,
use or application and disclaims any responsibility for their
application or use in any way.
5 AbbVie (2018). AbbVie Receives US FDA Accelerated
Approval for VENCLEXTA® (venetoclax) for Treatment of
Newly-Diagnosed Acute Myeloid Leukemia Patients Ineligible for
Intensive Chemotherapy.
https://news.abbvie.com/news/press-releases/abbvie-receives-us-fda-accelerated-approval-for-venclexta-venetoclax-for-treatment-newly-diagnosed-acute-myeloid-leukemia-patients-ineligible-for-intensive-chemotherapy.htm.
Accessed October 2020.
6 DiNardo CD, et al. A randomized, double-blind,
placeobo-controlled study of venetoclax with azacytidine vs
azacytidine in treatment-naïve patients with acute myeloid leukemia
ineligible for intensive therapy: VIALE-A. Presented at the EHA
25th Annual Congress.
7 DiNardo CD, et al. Azacitidine and Venetoclax
in Previously Untreated Acute Myeloid. N Engl J Med.
2020;383(7):617-629.
8 Wei AH, et al. Venetoclax plus LDAC for newly
diagnosed AML ineligible for intensive chemotherapy: a phase 3
randomized placebo-controlled
trial. https://ashpublications.org/blood/article/135/24/2137/454176/Venetoclax-plus-LDAC-for-newly-diagnosed-AML.
Accessed October 2020.
9 Wei AH, et al. A Phase III Study of Venetoclax Plus
Low-Dose Cytarabine in Previously Untreated Older Patients with
Acute Myeloid Leukemia (VIALE-C): A Six-Month Update.Presented at
the 2020 ASCO Virtual Meeting.
10 National Cancer Institute (2018). Acute
Myeloid Leukemia - SEER Stat Fact Sheets.
https://seer.cancer.gov/statfacts/html/amyl.html. Accessed
October 2020.
11 Pettit K, Odenike O. Defining and treating
older adults with acute myeloid leukemia who are ineligible for
intensive therapies. Front Oncol. 2015; 5:250.
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