- Phase 3 data from CLL14 study were highlighted in an
oral presentation (abstract #7502) today at ASCO and published in
the New England Journal of Medicine
- Patients treated with venetoclax plus obinutuzumab
lived significantly longer without their disease progressing, and
sustained that benefit after stopping treatment, compared to those
treated with obinutuzumab plus chlorambucil
- Rates of minimal residual disease negativity in
peripheral blood were higher in patients treated with venetoclax
plus obinutuzumab three months after treatment
completion1
NORTH CHICAGO, Ill.,
June 4, 2019 /PRNewswire/ -- AbbVie
(NYSE: ABBV), a research-based global biopharmaceutical company,
today presented data from the CLL14 trial, the first randomized
clinical trial to examine stopping an oral-based, chemotherapy-free
combination after 12 months in previously untreated patients with
CLL and coexisting medical conditions. The results demonstrate that
venetoclax plus obinutuzumab prolonged progression-free survival
(PFS) and achieved higher rates of complete response and minimal
residual disease (MRD)-negativity compared to a commonly used
standard of care obinutuzumab plus chlorambucil.1
These data were presented today in an oral presentation at the
American Society of Clinical Oncology (ASCO) Annual Meeting in
Chicago (abstract #7502) and were
simultaneously published in the New England Journal of Medicine
(NEJM).
"Conducting CLL14 was another collaborative and bold attempt to
continue pushing the boundaries of treatment in CLL," said
Mohamed Zaki, M.D., Ph.D., vice
president, global head of hematology development, AbbVie. "The
combination of venetoclax plus obinutuzumab significantly prolonged
progression-free survival and patients maintained that benefit
after stopping treatment. After the recent approval in the U.S., we
look forward to continue working with health authorities worldwide
as we aim to bring venetoclax plus obinutuzumab to patients with
previously untreated CLL."
The venetoclax and obinutuzumab combination was
recently approved by the U.S. Food and Drug Administration
(FDA) for previously untreated patients with CLL or small
lymphocytic lymphoma (SLL) based on results from the CLL14 clinical
trial.
In the CLL14 trial, investigator-assessed results demonstrated
that patients with CLL who were treated with venetoclax plus
obinutuzumab achieved superior PFS compared to patients treated
with obinutuzumab plus chlorambucil. Twenty-four-month PFS
estimates were 88.2 percent and 64.1 percent, respectively (hazard
ratio [HR]: 0.35, 95% confidence interval [CI]: 0.23, 0.53;
P<0.001). Higher rates of MRD-negativity were observed
with venetoclax plus obinutuzumab compared to obinutuzumab plus
chlorambucil in both peripheral blood (75.5 percent versus 35.2
percent, P<0.001) and bone marrow (56.9 percent versus
17.1 percent [P<0.001]) three months after treatment
completion, and complete response rates were significantly higher
with venetoclax plus obinutuzumab than with chlorambucil plus
obinutuzumab (49.5 percent versus 23.1 percent
[P<0.001]).1
"The combination of venetoclax plus obinutuzumab is a new and
rational approach to treat patients with previously untreated CLL
and coexisting medical conditions based on the results of the CLL14
trial," said Michael Hallek, M.D.,
chairman of the German CLL Study Group (DCLLSG), Department of
Internal Medicine and Center of Integrated Oncology at the
University Hospital Cologne in Germany, and lead study investigator. "The
CLL14 trial results show that a finite treatment duration induces a
longer time without progression when compared to a conventional
chemoimmunotherapy."
In the CLL14 trial, the adverse events (AEs) were consistent
with the known safety profiles of venetoclax and obinutuzumab
alone. At least one AE of any grade occurred in 94.3 percent of
patients in the venetoclax plus obinutuzumab arm. The most common
Grade 3/4 AEs in patients receiving venetoclax plus obinutuzumab
were febrile neutropenia (5.2 percent) and infections (17.5
percent). Tumor lysis syndrome (TLS) was reported in three patients
in the venetoclax plus obinutuzumab group (all during treatment
with obinutuzumab and before venetoclax).1 None of these
events met the Howard criteria for clinical TLS.2
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 Phase 3 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
investigational regimen of venetoclax plus obinutuzumab (n=216)
versus obinutuzumab plus chlorambucil (n=216) in previously
untreated patients with CLL and coexisting medical conditions. The
therapies were administered for a finite duration of 12 months for
venetoclax 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. The primary endpoint was PFS based on
investigator assessment, using iwCLL criteria.3
Key secondary endpoints were PFS as assessed by an independent
review committee, MRD-negativity in peripheral blood and bone
marrow, overall and complete response rates (OR and CR rates,
respectively), MRD-negativity in complete response in peripheral
blood and bone marrow, and overall survival (OS).
About VENCLEXTA®/VENCLYXTO®
(venetoclax)
VENCLEXTA®/VENCLYXTO® (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/VENCLYXTO
targets the BCL-2 protein and works to help restore the process of
apoptosis.4
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. 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 Information4
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 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 join 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.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.
Indication and Important VENCLYXTO (venetoclax) EU Safety
Information5
Indication
Venclyxto in combination with rituximab is
indicated for the treatment of adult patients with chronic
lymphocytic leukaemia (CLL) who have received at least one prior
therapy.
Venclyxto monotherapy is indicated for the treatment of CLL:
- in the presence of 17p deletion or TP53 mutation in adult
patients who are unsuitable for or have failed a B-cell receptor
pathway inhibitor, or
- in the absence of 17p deletion or TP53 mutation in adult
patients who have failed both chemoimmunotherapy and a B-cell
receptor pathway inhibitor.
Contraindications
Hypersensitivity to the active
substance or to any of the excipients is contraindicated.
Concomitant use of strong CYP3A inhibitors at initiation and during
the dose-titration phase due to increased risk for tumor lysis
syndrome (TLS). Concomitant use of preparations containing
St. John's wort as VENCLYXTO
efficacy may be reduced.
Special Warnings & Precautions for Use
Tumor lysis
syndrome (TLS), including fatal events, has occurred in patients
with previously treated CLL with high tumor burden when treated
with VENCLYXTO. VENCLYXTO poses a risk for TLS in the initial
5-week dose-titration phase. Changes in electrolytes consistent
with TLS that require prompt management can occur as early as 6 to
8 hours following the first dose of VENCLYXTO and at each dose
increase. Patients should be assessed for risk and should receive
appropriate prophylaxis, monitoring, and management for TLS.
Neutropenia (grade 3 or 4) has been reported and complete blood
counts should be monitored throughout the treatment period. Serious
infections including events of sepsis with fatal outcome have been
reported. Supportive measures including antimicrobials for any
signs of infection should be considered.
Live vaccines should not be administered during treatment or
thereafter until B-cell recovery.
Drug Interactions
CYP3A inhibitors may increase
VENCLYXTO plasma concentrations. At initiation and dose-titration
phase: Strong CYP3A inhibitors are contraindicated due to increased
risk for TLS and moderate CYP3A inhibitors should be avoided. If
moderate CYP3A inhibitors must be used, physicians should refer to
the SmPC for dose adjustment recommendations. At steady daily dose:
If moderate or strong CYP3A inhibitors must be used, physicians
should refer to the SmPC for dose adjustment recommendations.
Avoid concomitant use of P-gp and BCRP inhibitors at initiation
and during the dose titration phase.
CYP3A4 inducers may decrease VENCLYXTO plasma concentrations.
Avoid coadministration with strong or moderate CYP3A inducers.
These agents may decrease venetoclax plasma
concentrations.
Co-administration of bile acid sequestrants with VENCLYXTO is
not recommended as this may reduce the absorption of VENCLYXTO.
Adverse Reactions
The most commonly occurring adverse
reactions (>=20%) of any grade in patients receiving venetoclax
in the combination study with rituximab were neutropenia, diarrhea,
and upper respiratory tract infection. In the monotherapy studies,
the most common adverse reactions were neutropenia/neutrophil count
decreased, diarrhea, nausea, anemia, fatigue, and upper respiratory
tract infection.
The most frequently occurring serious adverse reactions
(>=2%) in patients receiving venetoclax in combination with
rituximab or as monotherapy were pneumonia, febrile neutropenia and
TLS.
Discontinuation due to adverse reactions occurred in 16% of
patients receiving venetoclax plus rituximab and 9% receiving
venetoclax monotherapy. Dosage adjustments due to adverse
reactions occurred in 15% of patients receiving venetoclax plus
rituximab and 2% receiving venetoclax monotherapy. Dose
interruptions occurred in 71% of patients treated with the
combination of venetoclax and rituximab.
Specific Populations
Patients with reduced renal
function (CrCl <80 mL/min) may require more intensive
prophylaxis and monitoring to reduce the risk of TLS. Safety in
patients with severe renal impairment (CrCl <30 mL/min) or on
dialysis has not been established, and a recommended dose for these
patients has not been determined. VENCLYXTO should be administered
to patients with severe renal impairment only if the benefit
outweighs the risk and patients should be monitored closely for
signs of toxicity due to increased risk of TLS.
VENCLYXTO may cause embryo-fetal harm when administered to a
pregnant woman. Advise nursing women to discontinue breastfeeding
during treatment.
This is not a complete summary of all safety information. See
VENCLYXTO full summary of product characteristics (SmPC) at
www.ema.europa.eu. 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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1 Fischer K, et al. Effect of
fixed-duration venetoclax plus obinutuzumab (VenG) on
progression-free survival (PFS), and rates and duration of minimal
residual disease negativity (MRD–) in previously untreated patients
(pts) with chronic lymphocytic leukemia (CLL) and comorbidities.
Presented at the 2019 American Society of Clinical Oncology Annual
Meeting: June 4, 2019; Chicago.
|
2 Howard SC, Jones DP, Pui CH. The
tumor lysis syndrome. N Engl J M
2011;364:1844-1854.
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3 Hallek
M, Cheson BD, Catovsky D, et al. Guidelines for diagnosis,
indications for treatment, response assessment and supportive
management of chronic lymphocytic leukemia. Blood.
2018;806398.
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4 VENCLEXTA (venetoclax) [Package
Insert].NorthChicago, IL.: AbbVie Inc.
|
5 Summary of Product Characteristics
for VENCLYXTO. Ludwigshafen, Germany: AbbVie Deutschland GmbH &
Co. KG.
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