NORTH CHICAGO, Ill.,
Dec. 5, 2020 /PRNewswire/ -- AbbVie
(NYSE: ABBV) today announced new, updated results from the Phase 3
MURANO and CLL14 clinical trials evaluating
VENCLEXTA®/VENCLYXTO® (venetoclax) fixed
duration treatment combinations at the virtual 62nd
American Society of Hematology (ASH) Annual Meeting &
Exposition (abstracts 125, 127, and 1310, respectively). These
findings add to the growing body of data supporting the use of
VENCLEXTA/VENCLYXTO in first-line or previously treated chronic
lymphocytic leukemia (CLL) patients.
"MURANO and CLL14 provide a look at the benefits of fixed
duration VENCLEXTA combinations in helping many patients to achieve
sustained progression-free survival," said John Hayslip, M.D.,
M.S.C.R., executive medical director, AbbVie. "These responses
reinforce that with VENCLEXTA/VENCLYXTO, it is possible for CLL
patients to complete treatment and live longer without their
disease progressing."
Data from the MURANO and CLL14 trials presented at ASH reinforce
that CLL patients who have relapsed or have not started treatment
and receive a VENCLEXTA/VENCLYXTO regimen can experience
long-lasting responses, even after stopping treatment, compared to
standard of care treatment options.
MURANO Five-Year Analysis1
The results of
the final, descriptive analysis of the MURANO trial (median
follow-up of 59.2 months with all patients off VENCLEXTA/VENCLYXTO
in combination with rituximab [VenR] treatment for at least three
years; Abstract 125) demonstrated the following:
- Investigator (INV)-assessed progression-free survival
(PFS): Patients with relapsed or refractory (R/R) CLL on fixed
duration VenR had a median PFS of 53.6 months (95% CI: 48.4-57.0)
compared to 17.0 months (95% CI: 15.5-21.7) with bendamustine plus
rituximab (BR; HR 0.19, 95% CI: 0.15-0.26).
- Overall survival (OS): The OS estimate was 82.1% (95%
CI: 76.4-87.8) with VenR compared to 62.2% (95% CI: 54.8-69.6) for
BR (HR 0.40, 95% CI: 0.26-0.62), median not reached in either
arm.
- Minimal residual disease (MRD) status at completion of VenR
treatment: Patients who achieved MRD-negativity without disease
progression at the end of their treatment course had improved PFS
and OS compared to patients with MRD. MRD refers to the small
number of cancer cells that remain in the body after treatment. The
number of remaining cells may be so small that they do not cause
any physical signs or symptoms and often cannot even be detected
through traditional methods.4
- Consistent safety profile: The safety profile of the
VenR combination is consistent with the known safety profile of
each individual therapy alone. No new, serious safety issues were
observed in the five-year MURANO updated analysis.
According to the Leukemia & Lymphoma Society, MRD refers to
the small number of cancer cells that remain in the body after
treatment.4 The number of remaining cells may be so
small that they do not cause any physical signs or symptoms and
often cannot even be detected through traditional methods, this is
known as undetectable MRD (uMRD). Doctors use MRD/uMRD to
measure the effectiveness of treatment and to predict which
patients are at risk of relapse.
CLL14
Analyses2,3
Data from
descriptive analyses of the Phase 3 CLL14 trial was also presented
today evaluating the role of MRD measurements in clinical
trials.
One analysis showed that patients with previously untreated CLL
and co-existing medical conditions who had partial response (PR)
after treatment with VENCLEXTA/VENCLYXTO in combination with
obinutuzumab (Ven-Obi) had a similar outcome as patients with
complete response (CR) when uMRD levels were achieved. These data
suggest that patients on the VENCLEXTA/VENCLYXTO combination with
uMRD levels and PR had longer PFS than patients with MRD and CR.
This is significant because patients with CLL who show a PR to
chemoimmunotherapy have a poorer prognosis than patients with
CR.2 These results were not tested for statistical
significance. (Abstract 1310)
The second analysis looked at clonal growth patterns – or how
quickly cancer cells grow and spread – in patients treated within
the CLL14 trial. The findings from the analysis shed light on which
patient group may be at risk of relapsing despite initial MRD
response.3 (Abstract 127)
The four-year, follow-up analysis showed an OS rate of 85.3%
with Ven-Obi versus 83.1% with chlorambucil in combination with
obinutuzumab (Obi-Clb; HR 0.85, 95% CI [0.54-1.35]; P=0.4929).
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 MURANO Trial5,6,7
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 VenR (n=194) compared with BR (n=195).
The median age of patients in the trial was 65 years (range: 22 to
85).
The trial met its primary efficacy endpoint of INV-assessed PFS.
At the time of the primary analysis, median PFS with VenR was not
reached compared with 17.0 months for BR (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.
In patients with CLL receiving combination therapy with
rituximab, the most frequent serious adverse reaction (AR; ≥5%) was
pneumonia (9%). The most common ARs (≥20%) of any grade were
neutropenia (65%), diarrhea (40%), upper respiratory tract
infection (39%), fatigue (22%), and nausea (21%). Fatal ARs that
occurred in the absence of disease progression and within 30 days
of the last venetoclax treatment and/or 90 days of the last
rituximab were reported in 2% (4/194) of patients.
About the CLL14 Trial6,7,8
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 Ven-Obi (n=216) versus Obi-Clb (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 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. Efficacy
was based on PFS as assessed by an IRC.
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 OS.
In patients with CLL receiving combination therapy with
obinutuzumab, serious ARs were most often due to febrile
neutropenia and pneumonia (5% each). The most common ARs (≥20%) of
any grade were neutropenia (60%), diarrhea (28%), and fatigue
(21%). Fatal ARs that occurred in the absence of disease
progression and with onset within 28 days of the last study
treatment were reported in 2% (4/212) of patients, most often from
infection.
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.
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.
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. When restarting
VENCLEXTA after stopping for 1 week or longer, your healthcare
provider may again check for your risk of TLS and change your
dose.
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 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 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 and for 1 week after the last dose of 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 and may pause
dosing.
- 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 nausea; diarrhea; low platelet count; constipation; low
white blood cell count; fever with low white blood cell count;
tiredness; vomiting; swelling of arms, legs, hands, or feet; fever;
infection in lungs; shortness of breath; bleeding; low red blood
cell count; rash; stomach (abdominal) pain; infection in your
blood; muscle and joint pain; dizziness; cough; sore throat; and
low blood pressure.
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. Call
your doctor for medical advice about side effects.
You are encouraged to report 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
genentech-access.com/patient/brands/venclexta for
assistance.
The full U.S. prescribing information, including Medication
Guide, for VENCLEXTA can be
found here.
See VENCLYXTO full summary of product characteristics (SmPC)
at
https://www.ema.europa.eu/en/documents/product-information/venclyxto-epar-product-information_en.pdf.
Globally, prescribing information varies; refer to the
individual country product label for complete information.
About AbbVie in Oncology
At AbbVie, we are committed
to transforming standards of care for multiple blood cancers while
advancing a dynamic pipeline of investigational therapies across a
range of cancer types. Our dedicated and experienced team joins
forces with innovative partners to accelerate the delivery of
potentially breakthrough medicines. We are evaluating more than 20
investigational medicines in over 300 clinical trials across some
of the world's most widespread and debilitating cancers. As we work
to have a remarkable impact on people's lives, we are committed to
exploring solutions to help patients obtain access to our cancer
medicines. For more information, please visit
http://www.abbvie.com/oncology.
About AbbVie
AbbVie's mission is to discover and
deliver innovative medicines that solve serious health issues today
and address the medical challenges of tomorrow. We strive to have a
remarkable impact on people's lives across several key therapeutic
areas: immunology, oncology, neuroscience, eye care, virology,
women's health and gastroenterology, in addition to products and
services across its Allergan Aesthetics portfolio. For more
information about AbbVie, please visit us at www.abbvie.com.
Follow @abbvie on Twitter, Facebook, Instagram, YouTube and LinkedIn.
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, failure to realize
the expected benefits from AbbVie's acquisition of Allergan plc
("Allergan"), failure to promptly and effectively integrate
Allergan's businesses, competition from other products, challenges
to intellectual property, difficulties inherent in the research and
development process, adverse litigation or government action,
changes to laws and regulations applicable to our industry and the
impact of public health outbreaks, epidemics or pandemics, such as
COVID-19. 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 2019 Annual Report on Form 10-K, which has been filed with
the Securities and Exchange Commission, as updated by its
subsequent Quarterly Reports on Form 10-Q. 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 Kater AP, et al. Abstract 125: Five-Year Analysis
of Murano Study Demonstrates Enduring Undetectable Minimal Residual
Disease (uMRD) in a Subset of Relapsed/Refractory Chronic
Lymphocytic Leukemia (R/R CLL) Patients (Pts) Following
Fixed-Duration Venetoclax-Rituximab (VenR) Therapy (Tx). Presented
at the 2020 American Society of Hematology Annual Meeting &
Exposition: December 5, 2020.
2 Al-Sawaf O, et al. Abstract 1310: Characteristics and
Outcome of Patients with Chronic Lymphocytic Leukaemia and Partial
Response to Venetoclax-Obinutuzumab. Presented at the 2020 American
Society of Hematology Annual Meeting & Exposition: December 5, 2020.
3 Al-Sawaf O, et al. Abstract 127: Clonal Dynamics after
Venetoclax-Obinutuzumab Therapy: Novel Insights from the
Randomized, Phase 3 CLL14 Trial. Presented at the 2020 American
Society of Hematology Annual Meeting & Exposition: December 5, 2020.
4 Leukemia and Lymphoma Society Minimal Residual Disease
(MRD) Fact Sheet
https://www.lls.org/sites/default/files/National/USA/Pdf/Publications/FS35_MRD_Final_2019.pdf
5 Seymour JF, et al. Venetoclax-rituximab in relapsed or
refractory chronic lymphocytic leukemia. N Engl J Med.
2018;378(12):1107-1120
6 Summary of Product Characteristics for VENCLYXTO
(venetoclax). Ludwigshafen, Germany: AbbVie Deutschland GmbH & Co.
KG.
7 VENCLEXTA (venetoclax) [Package Insert]. North Chicago, Ill.: AbbVie Inc.
8 Fischer K, et al. Venetoclax and Obinutuzumab in
Patients with CLL and Coexisting Conditions. N Engl J Med.
2019;380:2225-2236.
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