NORTH CHICAGO, Ill.,
Sept. 18, 2017 /PRNewswire/
-- AbbVie (NYSE: ABBV), a global research and
development-based biopharmaceutical company, today announced that
the Phase 3 MURANO study of VENCLEXTA™/VENCLYXTO™ (Venetoclax)
Tablets in combination with Rituxan® (rituximab) met its
primary endpoint. Results showed that VENCLEXTA/VENCLYXTO in
combination with Rituxan prolonged progression-free survival (PFS)
in patients with relapsed/refractory (R/R) chronic lymphocytic
leukemia (CLL) compared with bendamustine combined with Rituxan. An
independent data monitoring committee reviewed this study and made
the recommendation to unblind the trial based on the positive
results. Doctors will continue to monitor patients who remain
active in the MURANO trial in efforts to obtain additional,
longer-term safety and efficacy information.
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.
"AbbVie is committed to researching the full potential of
VENCLEXTA/VENCLYXTO both as monotherapy and combination
therapy in patients with CLL and other hematologic malignancies.
The analysis of the MURANO trial showed that
VENCLEXTA/VENCLYXTO in combination with Rituxan may offer
another option for patients with R/R CLL, potentially providing
them with a chemotherapy-free therapy," said Michael Severino, M.D., executive vice
president, research and development, and chief scientific officer,
AbbVie. "We are looking forward to working with regulatory
authorities around the world to bring this additional treatment
regimen to R/R CLL patients."
The most common type of leukemia in the Western world is CLL,
which accounts for approximately one-quarter of new cases of
leukemia in the U.S.1,2 CLL is a
slow-growing form of leukemia, or blood cancer, in which too many
immature lymphocytes (type of white blood cells) are found
predominantly in the blood and bone marrow.3 CLL usually affects older patients,
with more men than women affected. The median age at diagnosis is
approximately 70 years.1
Full data from this study will support regulatory submissions
for VENCLEXTA/VENCLYXTO in combination with Rituxan therapy
in R/R CLL, and will be presented at an upcoming medical
conference. Safety data, including serious and most common adverse
events and discontinuation rates, are currently being analyzed.
About the Phase 3 Study
The multicenter, open-label,
randomized Phase 3 MURANO study was designed to evaluate the
efficacy and safety of VENCLEXTA/VENCLYXTO in combination
with Rituxan compared with bendamustine in combination with Rituxan
in patients with R/R CLL.4 The primary endpoint was
investigator-assessed progression-free survival (PFS), which was
determined using standard International Workshop on Chronic
Lymphocytic Leukemia (iwCLL) guidelines. Secondary endpoints
included Independent Review Committee (IRC)-assessed PFS, as well
as PFS in patients with 17p deletion, best overall response
(defined as complete response [CR], complete response with
incomplete marrow recovery [CRi], nodular partial remission [nPR],
or PR), overall survival, event-free survival, duration of
response, time to next anti-CLL treatment, and percentage of
patients achieving minimal residual disease negativity.
About
VENCLEXTA™/VENCLYXTO™
VENCLEXTA/VENCLYXTO is an
oral B-cell lymphoma-2 (BCL-2) inhibitor that targets a specific
protein in the body called BCL-2. When you have CLL, BCL-2 may
build up and prevent cancer cells from self-destructing naturally.
VENCLEXTA/VENCLYXTO targets BCL-2 in order to help restore
the process of apoptosis. Through apoptosis, your body allows
cancer cells and normal cells to self-destruct.
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 with
venetoclax, which is currently being evaluated in clinical trials
in several hematologic cancers.
VENCLEXTA/VENCLYXTO is under evaluation by health
authorities in multiple countries, and is currently approved in 16
nations, including the U.S., and in the EU. AbbVie, in
collaboration with Roche and Genentech, is currently working with
regulatory agencies around the world to bring this medicine to
eligible patients in need.
About VENCLYXTO™ (venetoclax) Tablets (EU)
VENCLYXTO™
(venetoclax) is indicated in the European Union (EU) for the
treatment of chronic lymphocytic leukemia (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; and for the
treatment of CLL in the absence of 17p deletion or TP53 mutation in
adult patients who have failed both chemoimmunotherapy and a B-cell
receptor pathway inhibitor.5 It is also being evaluated for the
treatment of patients with various blood cancer
types.5,6,7,8,9 The
BCL-2 protein prevents apoptosis (programmed cell death) of some
cells, including lymphocytes, and can be overexpressed in CLL
cells.5 VENCLYXTO, which is given once-daily, is
designed to selectively inhibit the function of the BCL-2
protein.5
Important VENCLYXTO (venetoclax) EU Safety Information
Contraindications
Hypersensitivity to the active substance
or to any of the excipients. Concomitant use of strong CYP3A
inhibitors at initiation and during the dose-titration phase.
Concomitant use of preparations containing St. John's wort.
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 for TLS. Blood chemistries
should be monitored and abnormalities managed promptly. More
intensive measures (including IV hydration, frequent monitoring and
hospitalization) should be employed as overall risk increases.
Neutropenia (grade 3 or 4) has been reported and complete blood
counts should be monitored throughout the treatment
period.
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 co-administration 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 were neutropenia/neutrophil count
decreased, diarrhea, nausea, anemia, upper respiratory tract
infection, fatigue, hyperphosphatemia, vomiting and
constipation.
The most frequently occurring adverse reactions (>=2%) were
pneumonia, febrile neutropenia and TLS.
Discontinuations due to adverse reactions occurred in 9.1% of
patients and dosage adjustments due to adverse reactions occurred
in 11.8% of patients.
Specific Populations
VENCLYXTO may cause embryo-fetal harm when administered to a
pregnant woman. Advise females of reproductive potential to avoid
pregnancy during treatment. Advise nursing women to discontinue
breastfeeding during treatment.
Safety in patients with severe renal impairment or on dialysis
has not been established, and a recommended dose has not been
determined. VENCLYXTO should be administered to patients with
severe renal impairment only if the benefit outweighs the risk.
Monitor closely for signs of toxicity due to increased risk of
TLS.
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 VENCLEXTA™ (venetoclax) tablets (US)
In
April 2016, the U.S. Food and Drug
Administration (FDA) granted accelerated approval of VENCLEXTA™
(venetoclax) tablets 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.10 The FDA approved this indication
under accelerated approval based on overall response rate, and
continued approval may be contingent upon verification and
description of clinical benefit in a confirmatory trial.
In January 2016, AbbVie announced that the FDA granted
Breakthrough Therapy Designation (BTD) for venetoclax in
combination with rituximab for the treatment of patients with R/R
CLL.
What is VENCLEXTA™ (venetoclax)?
VENCLEXTA™ (venetoclax) is a prescription medicine used to treat
people with chronic lymphocytic leukemia (CLL) with 17p deletion
who have received at least one prior treatment.
VENCLEXTA was approved based on response rate. There is 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 VENCLEXTA™ (venetoclax) US 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 doctor will do
tests for TLS. It is important to keep your appointments for blood
tests. 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. Tell
your doctor 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.
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.
- Tell your doctor 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 doctor.
What should I tell my doctor before taking VENCLEXTA?
Before taking VENCLEXTA, tell your doctor about all of your
medical conditions, including if you:
- Have kidney or liver 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 doctor tells you it is okay. If you are not sure about
the type of immunization or vaccine, ask your doctor. 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 doctor
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.
- 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 count (neutropenia). Low white
blood cell counts are common with VENCLEXTA, but can also be
severe. Your doctor will do blood tests to check your blood counts
during treatment with VENCLEXTA. Tell your doctor right away if you
have a fever or any signs of an infection.
The most common side effects of VENCLEXTA
include low white blood cell count, diarrhea, nausea, low
red blood cell count, upper respiratory tract infection, low
platelet count, and feeling tired.
VENCLEXTA may cause fertility problems in males. This may affect
your ability to father a child. Talk to your doctor if you have
concerns about fertility.
These are not all the possible side effects of VENCLEXTA. Tell
your doctor if you have any side effect that bothers you or that
does not go away.
The full U.S. prescribing information for VENCLEXTA can be
found here. Globally, prescribing information varies;
refer to the individual country product label for complete
information.
Patient Assistance
For those who qualify, patient assistance options are available for
people taking VENCLEXTA in the U.S.
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://abbvieoncology.com.
About AbbVie
AbbVie is a global, research-driven
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 or LinkedIn.
AbbVie Forward-Looking Statements
Some statements in
this news release may be 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, challenges to intellectual property,
competition from other products, 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," in
AbbVie's 2016 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.
References
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https://www.cancer.org/cancer/chronic-lymphocytic-leukemia/about/key-statistics.html.
Accessed August 22, 2017.
3 NCI dictionary. NCI Dictionary of Terms. Chronic
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https://www.cancer.gov/publications/dictionaries/cancer-terms.
Accessed August 22, 2017.
4 Clinicaltrials.gov. NCT02005471: A Study of Venetoclax
in Combination With Rituximab Compared With Bendamustine in
Combination With Rituximab in Participants With Relapsed or
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ABT-199 in subjects with Acute Myelogenous Leukemia (AML). Accessed
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7 Clinicaltrials.gov. NCT01794520: Study evaluating
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8 Clinicaltrials.gov. NCT01328626: A Phase 1 study
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