NORTH CHICAGO, Ill.,
Aug. 12, 2020 /PRNewswire/ -- AbbVie
(NYSE: ABBV) today announced the publication of results from the
Phase 3 VIALE-A clinical study in patients with AML in the New
England Journal of Medicine (NEJM). The study,
which evaluated newly-diagnosed AML patients who had not yet been
treated and were unable to tolerate traditional intensive
chemotherapy, found that venetoclax in combination with azacitidine
extended overall survival (OS) compared to azacitidine plus
placebo. The manuscript titled, "Azacitidine and Venetoclax in
Previously Untreated Acute Myeloid Leukemia," was published in the
August 13, 2020 issue of
NEJM.3
"The ability of venetoclax plus azacitidine to improve outcomes
of newly-diagnosed AML patients unable to tolerate intensive
chemotherapy represents a potentially practice-changing advance in
AML treatment," said Courtney D.
DiNardo, M.D., MSCE, Department of Leukemia, Division of
Cancer Medicine at The University of
Texas MD Anderson Cancer Center and the lead study
investigator.
In the VIALE-A study, OS was the sole primary study endpoint in
the U.S. OS and composite complete remission rate (CR+CRi) were
co-primary endpoints in China,
Japan, the European Union (EU) and
EU reference countries. CR+CRi is a composite score reflecting the
complete remission (CR) and CR with incomplete hematologic recovery
(CRi), which is an incomplete CR with blood counts not fully
recovered.4,5 Treatment with venetoclax plus
azacitidine reduced the risk of death by 34% compared to
azacitidine in combination with placebo (Hazard Ratio [HR]=0.66
[95% CI: 0.52-0.85], p<0.001).3
Patients in the venetoclax combination arm had a median OS of
14.7 months (95% CI: 11.9-18.7) versus 9.6 months for patients in
the placebo arm (95% CI: 7.4-12.7). Additionally, 66.4% (95% CI:
60.6-71.9) of patients treated with venetoclax plus azacitidine
achieved CR+CRi versus 28.3% (95% CI: 21.1-36.3) of patients
treated with azacitidine plus placebo (p<0.001). Other
secondary endpoints that were published in NEJM include CR
and CR with partial hematologic recovery
(CR+CRh).3
The observed safety profile in the VIALE-A trial is generally
consistent with the known safety profiles of venetoclax combined
with azacitidine. The most common adverse events (AEs [occurring in
≥40% of patients]) in patients receiving venetoclax plus
azacitidine were mostly hematologic and gastrointestinal in nature
and consisted of thrombocytopenia (46%), nausea (44%), constipation
(43%), neutropenia (42%), febrile neutropenia (42%) and diarrhea
(41%). The most frequent serious adverse reactions (ARs [occurring
in >10% of patients]) in patients receiving venetoclax plus
azacitidine were febrile neutropenia (30%) and pneumonia
(17%). Tumor lysis syndrome (TLS) was reported during ramp-up
in three patients in the venetoclax arm and none in the placebo
arm. All were transient biochemical changes that resolved with
uricosuric agents – medications that increase excretion of uric
acid in the urine and decrease the concentration of uric acid in
blood plasma – and calcium supplements without treatment
interruption.
The VIALE-A trial results were presented as late-breaking data
during the virtual 25th European Hematology Association
(EHA) Annual Congress in June 2020
(abstract #LB2601).6 AbbVie, in collaboration with
Genentech, submitted the results of the VIALE-A (M15-656)
trial, along with data from the VIALE-C (M16-043) trial and updated
data from the Phase 1/2 studies M14-358 and M14-387, to the
U.S. Food and Drug Administration (FDA) to convert the accelerated
approval for venetoclax in combination with azacitidine,
decitabine, or low-dose cytarabine (LDAC) for the treatment of
newly-diagnosed AML in adults who are age 75 years or older, or who
have comorbidities that preclude use of intensive induction
chemotherapy, to a full approval. AbbVie also submitted these data
to additional health authorities around the world.
AML is the most common acute leukemia in the
world.7 Not all patients can tolerate standard
intensive chemotherapy,8 making it among the most
difficult blood cancers to treat.9 Despite advances
in available therapies and care, the five-year survival rate for
patients diagnosed with AML remains approximately
28%.10
Venetoclax, known by the brand name VENCLEXTA® in the U.S., 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 (M15-656) Phase 3 Trial
A total of 433 treatment-naïve, intensive chemotherapy ineligible
AML patients were randomized in the double-blind,
placebo-controlled Phase 3 VIALE-A trial. The trial was designed to
evaluate the efficacy and safety of venetoclax in combination with
azacitidine (n=286) compared with azacitidine in combination with
placebo (n=145).3
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/VENCLYXTO 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/VENCLYXTO is approved in more than 50
countries, including the U.S.
Uses and Important VENCLEXTA® (venetoclax) U.S. Safety
Information11
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.
VENCLEXTA was approved based on response rates. Continued
approval for this use may depend on the results of an ongoing study
to find out how VENCLEXTA works over a longer period of time.
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 with 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.
- 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 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 your 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
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. For
more information, ask your healthcare provider or pharmacist.
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 cannot afford your medication,
contact www.medicineassistancetool.org for
assistance.
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 strive to discover and develop medicines that deliver
transformational improvements in cancer treatment by uniquely
combining our deep knowledge in core areas of biology with
cutting-edge technologies, and by working together with our
partners – scientists, clinical experts, industry peers, advocates,
and patients. We remain focused on delivering these transformative
advances in treatment across some of the most debilitating and
widespread cancers. We are also committed to exploring solutions to
help patients obtain access to our cancer medicines. AbbVie's
oncology portfolio now consists of marketed medicines and a
pipeline containing multiple new molecules being evaluated
worldwide in more than 300 clinical trials and more than 20
different tumor types. 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.
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H, et al. Acute myeloid leukemia. N Engl J Med.
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Accessed November 2018.
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3 DiNardo CD, et al. Azacitidine and
Venetoclax in Previously Untreated Acute Myeloid. N Engl J Med.
2020;383(7):617-629.
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4 Medeiros B (2018). Interpretation
of clinical endpoints in trials of acute myeloid leukemia
https://www.sciencedirect.com/science/article/pii/S0145212618300304.
Accessed June 2020.
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5 TechOverflow. What is Composite
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https://techoverflow.net/2019/11/22/what-is-composite-complete-remission-crc-in-cancer-research/.
Accessed June 2020.
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6 DiNardo CD, et al. A randomized,
double-blind, placebo-controlled study of venetoclax with
azacitidine vs. azacitidine in treatment-naïve patients with acute
myeloid leukemia ineligible for intensive therapy: VIALE-A. Oral
LB2601. 25th EHA Congress. June 11-21, 2020.
https://library.ehaweb.org/eha/2020/eha25th/303390/courtney.dinardo.a.randomized.double-blind.placebo-controlled.study.of.html?
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Cancer Institute. Adult Acute Myeloid Leukemia Treatment
(PDQ)-Patient Version.
https://www.cancer.gov/types/leukemia/patient/adult-aml-treatment-pdq.
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Treatment Response Rates for Acute Myeloid Leukemia (AML).
https://www.cancer.org/cancer/acute-myeloid-leukemia/treating/response-rates.html.
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Typical Treatment of Most Types of Acute Myeloid Leukemia (Except
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M3). https://www.cancer.org/cancer/acute-myeloid-leukemia/treating/typical-treatment-of-aml.html.
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11 VENCLEXTA (venetoclax) [Package
Insert]. North Chicago, IL.: AbbVie Inc.
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