NORTH CHICAGO, Ill.,
March 23, 2020 /PRNewswire/
-- AbbVie (NYSE: ABBV), a research-based global
biopharmaceutical company, today announced the VIALE-A (M15-656)
trial of VENCLEXTA® (venetoclax) in combination with
azacitidine versus azacitidine in combination with placebo met its
dual primary endpoints of statistically significant improvement of
overall survival (OS) and composite complete remission rate (CR +
CRi) for patients with previously-untreated acute myeloid leukemia
(AML) who are ineligible for intensive chemotherapy. At the
recommendation of an independent data monitoring committee (IDMC),
and per the prespecified interim analysis plan, due to positive
efficacy results at the first interim analysis for overall
survival, the trial results will be reported early, and the data
from the trial will be submitted to the U.S. FDA and global
health authorities. Results will be presented at a future medical
meeting or published in a peer-reviewed journal.
"For the past three decades, there has been few options for
patients with AML who cannot receive or tolerate intensive
chemotherapy or a bone marrow transplant," said Neil Gallagher, M.D., Ph.D., chief medical
officer and vice president of development, AbbVie. "The positive
results from VIALE-A support the clinical benefit of the venetoclax
plus azacitidine combination in patients with AML who are
ineligible for intensive chemotherapy and reflect our ongoing
commitment to transform the standards of care for patients with
hematologic malignancies."
AML is one of the most aggressive and difficult-to-treat blood
cancers with a very low survival rate.1,2 Despite
advances in available therapies and care, the 5-year survival rate
for patients diagnosed with AML remains approximately
28%.3 AML typically worsens quickly, and due to age
and comorbidities, not all patients are eligible to receive
intensive chemotherapy.4 AML is the most common
acute leukemia in the world.5 An estimated 160,000
people are currently living with the disease globally with an
incidence rate of 103 new cases per 100,000
people.5
The Phase 3 VIALE-A study evaluated the efficacy and safety of
venetoclax in combination with azacitidine compared with placebo in
combination with azacitidine. The study met its dual primary
endpoints of OS and composite complete remission (CR + CRi). At the
recommendation of an IDMC, and per the prespecified interim
analysis plan, due to positive efficacy results at the first
interim analysis for overall survival, the trial results will be
reported early, and the data from the trial will be submitted
to the U.S. FDA and global health authorities. The observed
safety profile is generally consistent with the known safety
profile of venetoclax combined with azacitidine as observed in
previous Phase 1/2 studies and the known safety profiles of the two
medications.
In November 2018, AbbVie received
accelerated approval in the U.S. for VENCLEXTA 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 based on the Phase 1/2 studies. Approval was
also granted in Mexico,
Israel, Puerto Rico, Peru, Brazil,
Russia, Argentina, Guatemala, Uruguay, Lebanon, Bahrain, Kazakhstan, Panama, Saudi
Arabia, Taiwan,
Australia, Qatar, and United
Arab Emirates.
The Phase 3 VIALE-A and VIALE-C (M16-043) studies were conducted
as confirmatory trials following the accelerated U.S. FDA approval
of venetoclax in AML in 2018. In February
2020, AbbVie provided an update on the Phase 3 VIALE-C study
of venetoclax in combination with LDAC compared with LDAC in
combination with placebo.
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.
About the VIALE-A (M15-656) Phase 3
Trial
A total of 443 treatment-naïve AML patients were
enrolled and 433 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=287) compared with placebo in combination with
azacitidine (n=146).6
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
Information7
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 when taking 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 health care 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 health care provider.
Before taking VENCLEXTA, tell your healthcare provider about
all of your medical conditions, including if you:
- have kidney 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 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 http://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 is a global, research and
development-based biopharmaceutical company committed to developing
innovative advanced therapies for some of the world's most complex
and critical conditions. The company's mission is to use its
expertise, dedicated people and unique approach to innovation to
markedly improve treatments across four primary therapeutic areas:
immunology, oncology, virology and neuroscience. In more than
75 countries, AbbVie employees are working every day to advance
health solutions for people around the world. For more information
about AbbVie, please visit us at www.abbvie.com. Follow
@abbvie on Twitter, Facebook, LinkedIn or Instagram.
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, competition from
other products, challenges to intellectual property, difficulties
inherent in the research and development process, adverse
litigation or government action, and changes to laws and
regulations applicable to our industry. 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 2018 Annual Report on Form
10-K, which has been filed with the Securities and Exchange
Commission. 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 Döhner H, et al. Acute myeloid leukemia. N
Engl J Med. 2015;373(12):1136-1152.
2 American Cancer Society (2018). 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.
3 National Cancer Institute (2018). Acute Myeloid
Leukemia - SEER Stat Fact
Sheets. https://seer.cancer.gov/statfacts/html/amyl.html.
4 Pettit, K and Odenike, O. Defining and Treating Older
Adults with Acute Myeloid Leukemia Who Are Ineligible for Intensive
Therapies. Front Oncol. 2015; 5:250.
5 Puty, T.C., Sarraf, J.S., Do Carmo Almeida, T.C. et
al. Evaluation of the impact of single-nucleotide polymorphisms on
treatment response, survival and toxicity with cytarabine and
anthracyclines in patients with acute myeloid leukaemia: a
systematic review protocol. Syst Rev 8, 109 (2019).
6 ClinicalTrials.gov (2019). NCT02993523: A Study
of Venetoclax in Combination With Azacitidine Versus Azacitidine in
Treatment Naïve Subjects With Acute Myeloid Leukemia Who Are
Ineligible for Standard Induction Therapy.
https://clinicaltrials.gov/ct2/show/NCT02993523.
7 VENCLEXTA (venetoclax) [Package Insert].
North Chicago, IL.: AbbVie
Inc.
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