NORTH CHICAGO, Ill.,
Dec. 8, 2019 /PRNewswire/ -- AbbVie
(NYSE: ABBV), a research-based global biopharmaceutical company,
today presented long-term data from a post-hoc analysis, further
supporting the sustained clinical benefit of fixed duration
treatment with VENCLEXTA®/VENCLYXTO® (venetoclax) in combination
with rituximab (VenR) in patients with relapsed or refractory
chronic lymphocytic leukemia (R/R CLL). The updated data from the
Phase 3 MURANO trial four-year analysis (median follow-up of 48
months with all patients off VENCLEXTA/VENCLYXTO treatment for a
median of 22 months) showed that patients with R/R CLL who
completed the chemotherapy-free, two-year fixed duration course of
VENCLEXTA/VENCLYXTO treatment combination maintained
progression-free survival (PFS) and overall survival (OS). Patients
who completed treatment with the VENCLEXTA/VENCLYXTO combination
also achieved higher rates of minimal residual disease
(MRD)-negativity and complete remissions compared to those treated
with a standard of care, bendamustine plus rituximab
(BR).1 The full results were presented today at the
61st American Society of Hematology (ASH) Annual Meeting
& Exposition (abstract #355).
"These results support the benefits of a fixed duration of
treatment with venetoclax to reduce the risk of disease progression
or death in patients with chronic lymphocytic leukemia," said
Mohammed Zaki, M.D., Ph.D., vice
president, global head of hematology development at AbbVie. "We
remain committed to understanding the full utility of venetoclax
combinations and to advancing other clinical development programs
with the potential to transform the standards of care
for patients with blood cancers."
"In the four-year analysis from the MURANO trial, treatment with
the venetoclax combination resulted in an 81 percent reduction in
the risk of progression or death compared to the standard of care,"
said Professor John Seymour, MBBS,
Ph.D., lead investigator of the MURANO trial and director of the
Department of Hematology at the Peter MacCallum Cancer Centre and
Royal Melbourne Hospital in Australia. "The sustained efficacy and
manageable safety profile observed in the study further
support the clinical benefits of fixed treatment in patients
with relapsed or refractory chronic lymphocytic
leukemia."
In the post-hoc analysis, median follow-up for patients who
completed two years of treatment with the venetoclax combination
without progressive disease (n=130) was 22 months (range: 1 to 35
months). PFS (HR, 0.19, 95% CI: 0.14, 0.25, descriptive
p<0.0001) and OS (HR 0.41, 95% CI: 0.26,0.65, descriptive
p<0.0001) remained durable for patients taking VenR compared to
those taking BR. Twenty-four months after patients were off
therapy, the investigator (INV)-assessed estimated PFS was 57.3%
(95% CI 49.4, 65.3) versus estimated PFS of 4.6% (95% CI, 0.1,
9.2) in patients taking BR. Additionally, the OS analysis showed a
four-year event-free rate of 85.3% (95% CI: 89.2, 99.0) in the
venetoclax arm compared to 66.8% for BR (medians not reached). The
improvements in both PFS and OS were observed despite 79% of
patients in the control arm receiving an additional targeted CLL
treatment after disease progression.1
By the end of treatment, 64% of patients had achieved
MRD-negativity, and 87% of those patients remained free of disease
progression two years post-treatment.1 MRD-negativity is
defined as the presence of less than one CLL cell in 10,000 white
blood cells remaining in the blood or bone marrow following
treatment. Achieving MRD-negativity was assessed as a secondary
endpoint because it is associated with improved clinical
outcomes.2 Higher rates of MRD-negativity were observed
off treatment in patients taking VenR than in those taking standard
of care BR.1
The safety profile of the combination is consistent with the
known safety profile of each individual therapy alone. There were
no new serious safety issues observed in the MURANO study since the
last update. Excluding non-melanoma skin cancer, there was one
report of melanoma in the standard of care cohort, and one report
of melanoma and one report of breast cancer in the venetoclax
combination cohort.1
Venetoclax, a first-in-class oral B-cell lymphoma-2 (BCL-2)
inhibitor, is being developed by AbbVie and Roche. It is jointly
commercialized by AbbVie and Genentech, a member of Roche Group, in
the U.S. and by AbbVie outside the U.S.
Design and Results of the Phase 3 MURANO Trial
A
total of 389 patients with R/R CLL who had received at least one
prior therapy were enrolled in the international, multicenter,
open-label, randomized Phase 3 MURANO trial. The trial was designed
to evaluate the efficacy and safety of venetoclax in combination
with rituximab (n=194) compared with bendamustine in combination
with rituximab (n=195). The median age of patients in the trial was
65 years (range: 22 to 85).3
The primary efficacy endpoint was INV-assessed PFS. At the time
of the primary analysis, median PFS with venetoclax in combination
with rituximab was not reached compared with 17.0 months for
bendamustine in combination with rituximab (HR: 0.17; 95% CI: 0.11,
0.25; p<0.0001). In the primary efficacy analysis, the median
follow-up for PFS was 23.8 months (range: 0 to 37.4). Additional
efficacy endpoints included independent review committee
(IRC)-assessed PFS, INV- and IRC-assessed overall response rate
(defined as complete response + complete response with incomplete
marrow recovery + partial response + nodular partial response), OS
and rates of MRD-negativity.3
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.
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 Information[4]
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 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.medicineassistancetool.org for assistance.
The full U.S. prescribing information, including Medication
Guide, for VENCLEXTA can be found here.
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. For patients with severe
(Child-Pugh C) hepatic impairment, a dose reduction of at
least 50% throughout treatment is recommended.
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. 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.
1Seymour JF, et al. Four-Year Analysis of Murano
Study Confirms Sustained Benefit of Time-Limited
Venetoclax-Rituximab (VenR) in Relapsed/Refractory (R/R) Chronic
Lymphocytic Leukemia (CLL). Presented at the 2019 American Society
of Hematology Annual Meeting & Exposition: December 8, 2019; Orlando.
2Hallek 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.
3Seymour JF, Kipps TJ, Eichhorst B, et al.
Venetoclax-rituximab in relapsed or refractory chronic lymphocytic
leukemia. N Engl J Med. 2018;378(12):1107-1120.
4VENCLEXTA (venetoclax) [Package
Insert]. North Chicago, IL.: AbbVie Inc.
5Summary of Product Characteristics for VENCLYXTO
(venetoclax). Ludwigshafen, Germany: AbbVie Deutschland GmbH
& Co. KG.
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