NORTH CHICAGO, Ill.,
May 15, 2019 /PRNewswire/ -- AbbVie
(NYSE: ABBV), a research-based global biopharmaceutical company,
today announced that the U.S. Food and Drug Administration (FDA)
has approved VENCLEXTA® (venetoclax) in combination with
obinutuzumab (GAZYVA®) for previously untreated patients with
chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma
(SLL).1 The FDA granted Breakthrough
Therapy designation for this combination therapy, and early
submission of the data was provided under the Real-Time Oncology
Review (RTOR) pilot program, which led to approval in just over two
months, following submission of the complete application.
"This FDA approval provides a new chemotherapy-free combination
treatment option for patients, and underscores the growing utility
of VENCLEXTA in CLL," said Michael
Severino, M.D., vice chairman and president, AbbVie.
"The approval is based on findings from the CLL14 trial in
which patients received a 12-month treatment regimen. The majority
of patients receiving VENCLEXTA in the trial remained
progression-free at two years."
Data from the CLL14 trial is expected to be presented at an
upcoming medical meeting and published in a journal this year.
"Patients never treated for their CLL have had to rely largely
on chemotherapy as their initial treatment," said Michael Hallek, M.D., lead investigator of the
CLL14 study, Department of Internal Medicine and Center of
Integrated Oncology at the University Hospital Cologne in
Germany, and Head of the German
CLL Study Group. "The approval of the VENCLEXTA combination means
that patients with previously untreated CLL now have a finite
duration, chemotherapy-free treatment option that can allow them to
live longer without disease progression, induce high rates of
minimal residual disease (MRD) negativity and, importantly,
allow them to complete their course of therapy within 12 months.
This is a major step forward in how previously untreated CLL is
managed and further supports the growing benefits offered by
VENCLEXTA in CLL."
The CLL14 trial demonstrated superior progression-free survival
as assessed by an independent review committee (PFS; the time from
initiation of treatment until disease progression or death) in
patients treated with VENCLEXTA plus obinutuzumab compared to
patients who received chlorambucil plus obinutuzumab,
a commonly used standard of care. With a median follow-up of
28 months (range: 0.1 to 36 months), VENCLEXTA plus obinutuzumab
reduced the risk of progression or death by 67% compared with
chlorambucil plus obinutuzumab (hazard ratio: 0.33, 95% confidence
interval [CI]: 0.22, 0.51; p<0.0001).1 Median
PFS was not reached in either treatment
arm.1 Minimal residual disease (MRD)
negativity (undetectable disease in the blood or bone marrow) was
assessed as a secondary endpoint and occurs when less than one CLL
cell per 10,000 leukocytes can be detected using sensitive
analytical methods. Higher rates of MRD negativity were
observed with VENCLEXTA plus obinutuzumab compared to obinutuzumab
plus chlorambucil in both bone marrow (57% versus 17%, p<0.0001)
and peripheral blood (76% versus 35%, p<0.0001) three months
after treatment completion .1
In the CLL14 trial, adverse events (AEs) were consistent with
the known safety profiles of VENCLEXTA and obinutuzumab alone.
Serious adverse reactions (ARs) were reported in 49% of patients in
the VENCLEXTA plus obinutuzumab arm, most often due to febrile
neutropenia and pneumonia (5% each). The most common ARs (≥15%) of
any grade were neutropenia (60%), diarrhea (28%), fatigue (21%),
nausea (19%), anemia (17%), and upper respiratory tract infection
(17%).1
VENCLEXTA, an oral B-cell lymphoma-2 (BCL-2) inhibitor, has been
granted five Breakthrough Therapy designations from the
FDA.2,3,4,5,6
Venetoclax is being developed by AbbVie and Roche and 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 Chronic Lymphocytic Leukemia
CLL is
typically a slow-progressing cancer of the bone marrow and blood in
which types of white blood cells called B lymphocytes become
cancerous and multiply abnormally.7 In the U.S., CLL
accounts for more than 20,000 newly diagnosed cases of leukemia
each year.7
About the CLL14 Trial
The prospective,
multicenter, open-label, randomized Phase 3 CLL14 trial, which was
conducted in close collaboration with the German CLL Study Group
(DCLLSG), evaluated the efficacy and safety of a combined regimen
of VENCLEXTA and obinutuzumab (n=216) versus obinutuzumab and
chlorambucil (n=216) in previously untreated patients with CLL and
coexisting medical conditions (total Cumulative Illness Rating
Scale [CIRS] score >6 or creatinine clearance <70 mL/min).
The therapies were administered for a fixed duration of 12 months
for VENCLEXTA in combination with six cycles of obinutuzumab. The
trial enrolled 432 patients, all of whom were previously untreated
according to the International Workshop on Chronic Lymphocytic
Leukemia (iwCLL) criteria. Efficacy was based on progression-free
survival (PFS) as assessed by an Independent Review Committee
(IRC).1,8
Key secondary endpoints were MRD negativity in peripheral blood
and bone marrow, overall and complete response rates, MRD
negativity in complete response in peripheral blood and bone
marrow, and overall survival.8
About VENCLEXTA® (venetoclax tablets) (US)
VENCLEXTA®
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.1
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. Venetoclax is being studied in several other hematologic
malignancies including acute myeloid leukemia (AML), multiple
myeloma (MM), non-Hodgkin lymphoma (NHL) and myelodysplastic
syndrome (MDS).9,10,11,12,13
In April 2016, the U.S. FDA first
granted accelerated approval of VENCLEXTA for the treatment of
patients with CLL with 17p deletion, as detected by an FDA-approved
test, who have received at least one prior therapy.14
The FDA approved this indication under accelerated approval based
on overall response rate.14 Based on the results of the
MURANO study, VENCLEXTA was approved in June
2018 for the treatment of patients with CLL or SLL, with or
without 17p deletion, who have received at least one prior
therapy.1 In November
2018, VENCLEXTA was approved 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.15
Venetoclax 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 Safety Information (US)
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 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.pparx.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. With the acquisitions of Pharmacyclics in
2015 and Stemcentrx in 2016, our research and development efforts,
and through collaborations, AbbVie's oncology portfolio now
consists of marketed medicines and a pipeline containing multiple
new molecules being evaluated worldwide in more than 200 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.
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