NORTH CHICAGO, Ill.,
Feb. 28, 2020 /PRNewswire/ -- AbbVie
(NYSE: ABBV), a research-based global biopharmaceutical company,
today announced the VIALE-C (M16-043) trial of venetoclax
(VENCLEXTA®) in combination with low-dose cytarabine
(LDAC) versus LDAC in combination with placebo did not meet its
primary endpoint of statistically significant improvement of
overall survival (OS) for patients with acute myeloid leukemia
(AML) who are ineligible for intensive chemotherapy at the time of
the planned analysis.3
Treatment with the venetoclax combination showed a 25% reduction
in the risk of death compared to LDAC with placebo (Hazard Ratio
[HR]=0.75 [95% CI 0.52–1.07], p=0.11). The venetoclax with LDAC arm
also showed a median OS of 7.2 months vs. 4.1 months in the LDAC
arm alone. A post-hoc analysis after an additional six months of
follow up showed an increase in median OS of 8.4 months in the
venetoclax plus LDAC arm and 4.1 months in the placebo plus LDAC
arm (HR=0.70 [95% CI 0.50-0.99]).3 Select secondary
endpoints are included in the following table.
Select Secondary Endpoint Outcomes:*
Outcome
|
Venetoclax plus
LDAC
(n=143)
|
Placebo plus LDAC
(n=68)
|
Complete
Remission
|
27.3%
|
7.4%
|
Complete Remission or
Complete Remission with Incomplete Blood Count Recovery (CR +
CRi)
|
47.6%
|
13.2%
|
Complete Remission or
Complete Remission with Partial Hematologic Recovery (CR +
CRh)
|
46.9%
|
14.7%
|
Complete Remission or
Complete Remission with Incomplete Blood Count (CR + CRi) by
Initiation of Cycle 2
|
34.3%
|
2.9%
|
The safety profile of the combination is consistent with the
safety results reported in the Phase 1/2 studies that supported the
U.S. Food and Drug Administration (FDA) approval of the
combination. At this time, indications for venetoclax remain
unchanged.
"We remain committed to AML patients and our research in AML and
other blood cancers," said Neil
Gallagher, M.D., Ph.D., chief medical officer and vice
president of development, AbbVie. "The study results, while not
statistically significant, are indicative of the clinical activity
of venetoclax in combination with low-dose cytarabine."
The VIALE-C study evaluated venetoclax in combination with LDAC
compared with LDAC alone in newly-diagnosed patients with AML who
are ineligible for intensive chemotherapy. The median follow-up
time at the end of the planned primary analysis for both arms of
the trial was 12 months. Select secondary endpoints that were
evaluated in the primary analysis included remission rates,
transfusion independence, and event-free survival.
Consistent with prior studies in AML, the most frequently
reported AEs, irrespective of cause, were hematologic and are
represented in the following table.
Serious and Non-Serious Adverse Events
|
Venetoclax plus LDAC
(n=142)
|
Placebo plus LDAC
(n=68)
|
AE's
|
Non-Serious
|
Serious
|
Non-Serious
|
Serious
|
Febrile
neutropenia
|
15.5%
|
16.9%
|
11.8%
|
17.7%
|
Neutropenia
|
45.8%
|
2.8%
|
17.7%
|
0
|
Thrombocytopenia
|
40.9%
|
4.9%
|
36.8%
|
2.9%
|
Anemia
|
26.1%
|
2.8%
|
22.1%
|
0
|
AML is one of the most difficult-to-treat blood cancers. It
forms in the bone marrow and results in increasing numbers of
abnormal white blood cells in the bloodstream and bone
marrow.4 AML typically worsens quickly and not all
patients are eligible to receive intensive chemotherapy. Age and
comorbidities are common factors limiting intensive
therapy.5 Only approximately 28 percent of patients
survive five years or more.6
In November 2018, AbbVie received
accelerated approval for VENCLEXTA in the U.S. in combination with
azacitidine, decitabine, or 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 Phase 1/2 studies. Continued approval for
this indication may be contingent upon verification and description
of clinical benefit in an ongoing trial. Approval was also granted
in Mexico, Israel, Puerto
Rico, Peru, Brazil, Russia, Argentina, Guatemala, Uruguay, Lebanon, Bahrain, Kazakhstan, Panama, Saudi
Arabia, Taiwan,
Australia, and United Arab Emirates. AbbVie has provided the
results from VIALE-C to the FDA and other global health authorities
and will continue to work with them to ensure that venetoclax
remains an appropriately managed option for patients with AML.
AbbVie has a robust AML clinical research program and is
continuing to explore the potential of venetoclax and other
investigational medicines in AML with several studies, including
VIALE-A, a Phase 3 study of venetoclax in combination with
azacitidine compared to azacitidine plus placebo in newly-diagnosed
patients who are ineligible for intensive chemotherapy.
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-C (M16-043) Phase 3 Trial
A total of 211 treatment-naïve AML patients were enrolled and 210
were treated in the randomized, double-blind, placebo-controlled
Phase 3 VIALE-C trial. The trial was designed to evaluate the
efficacy and safety of venetoclax in combination with low dose
cytarabine (LDAC) (N=143) compared with placebo in combination with
LDAC (N=68). The primary efficacy endpoint was overall survival
(OS) compared between the groups of patients receiving LDAC and
those who received LDAC with venetoclax.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 is approved in more than 50 countries, including the
U.S. AbbVie, in collaboration with Roche, is currently working
with regulatory agencies around the world to bring this medicine to
additional eligible patients in need.
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 Clinicaltrials.gov. NCT03069352: A Study of
Venetoclax in Combination With Low Dose Cytarabine Versus Low Dose
Cytarabine Alone in Treatment Naive Patients With Acute Myeloid
Leukemia Who Are Ineligible for Intensive
Chemotherapy.https://clinicaltrials.gov/ct2/show/results/NCT03069352.
Accessed February 28, 2020.
4 American Cancer Society (2018). What is Acute Myeloid
Leukemia (AML)?
https://www.cancer.org/cancer/acute-myeloid-leukemia/about/what-is-aml.html
5 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.
6 National Cancer Institute (2018). Acute Myeloid
Leukemia - SEER Stat Fact Sheets.
https://seer.cancer.gov/statfacts/html/amyl.html.
7 VENCLEXTA (venetoclax) [Package Insert]. North Chicago, IL.: AbbVie Inc.
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