NORTH CHICAGO, Ill.,
June 8, 2018 /PRNewswire/ -- AbbVie
(NYSE: ABBV), a research-based global biopharmaceutical company,
today announced the U.S. Food and Drug Administration (FDA) has
approved, under priority review, VENCLEXTA® (venetoclax tablets) in
combination with rituximab for the treatment of patients with
chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma
(SLL), with or without 17p deletion, who have received at least one
prior therapy.1
The approval is based on MURANO Phase 3 clinical trial data
which demonstrated a significant improvement in progression-free
survival (PFS) for relapsed/refractory (R/R) CLL patients, reducing
the risk of disease progression or death by 81 percent when
compared to bendamustine in combination with rituximab, a standard
of care chemoimmunotherapy regimen.1
Clinical trial patients who received VENCLEXTA plus rituximab
also achieved an overall response rate (ORR) of 92 percent and
those who received the chemoimmunotherapy regimen achieved an ORR
of 72 percent.1
The safety profile of the combination is consistent with the
known safety profile of VENCLEXTA. The most common adverse
reactions (ARs), greater than or equal to 20 percent, with
VENCLEXTA in combination with rituximab were neutropenia, diarrhea,
upper respiratory tract infection, fatigue, cough and
nausea.1
VENCLEXTA plus rituximab is the first oral-based,
chemotherapy-free combination in CLL that allows patients an option
for fixed treatment duration.
"VENCLEXTA now gives indicated patients a new opportunity to
significantly reduce the risk of their disease progressing,
compared to a current standard of care. This combination provides
previously treated CLL or SLL patients with a chemotherapy-free,
fixed duration treatment allowing patients the ability to stop
treatment after approximately two years," said Michael Severino, M.D., executive vice
president, research and development, and chief scientific officer,
AbbVie. "This is an important step for patients and we look forward
to continuing to provide new treatment options for people living
with difficult-to-treat blood cancers."
VENCLEXTA has been granted four Breakthrough Therapy
Designations (BTDs) from the FDA including for the combination
treatment regimen of VENCLEXTA plus rituximab for patients with R/R
CLL.2 The approval of the VENCLEXTA plus rituximab
treatment regimen marks the second approval granted under priority
review by the FDA for VENCLEXTA. Outside of the U.S., regulatory
submissions to and reviews with health authorities are
underway.
"The approval of the combination of VENCLEXTA plus rituximab for
patients with relapsed/refractory CLL or SLL validates the results
seen in the Phase 3 trial, including the significant improvement in
progression-free survival over a standard of care comparator arm,"
said Prof. John Seymour, MBBS,
Ph.D., lead investigator of the MURANO study and Director of Cancer
Medicine at the Peter MacCallum Cancer Centre & Royal Melbourne
Hospital in Australia.
"Progression-free survival is considered a gold standard for
demonstrating clinical benefit in oncology."
CLL is typically a slow-progressing cancer of the bone marrow
and blood in which types of white blood cells called lymphocytes
become cancerous and multiply abnormally.3 In the U.S.,
CLL accounts for more than 20,000 newly diagnosed cases of leukemia
each year.3 SLL is closely related to
CLL. However, unlike CLL, SLL cancer cells are typically found in
the lymph nodes and spleen rather than the bone marrow and the
blood. In the U.S., approximately 5,000 cases of SLL are diagnosed
annually.4
The FDA has also approved expansion of the indication of
VENCLEXTA as monotherapy for CLL or SLL patients, with or without
17p deletion, who have received one prior therapy. Previously,
VENCLEXTA, the first B-cell lymphoma-2 (BCL-2) inhibitor in CLL,
was approved under accelerated approval in the U.S. in April 2016 as a monotherapy 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.5
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 Study
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 (1:1) MURANO study (NCT02005471). The study
was designed to evaluate the efficacy and safety of VENCLEXTA in
combination with rituximab (194 patients) compared with
bendamustine in combination with rituximab (195 patients). The
median age of patients in the trial was 65 years (range
22-85).1
Efficacy in the U.S. was based on PFS as assessed by an
Independent Review Committee (IRC). Median PFS with VENCLEXTA in
combination with rituximab was not reached, compared with 18.1
months for bendamustine in combination with rituximab (hazard
ratio: 0.19; 95% confidence interval [CI]: 0.13, 0.28;
P<0.0001). The median follow-up for PFS was 23.4 months (range:
0 to 37.4+ months). Additional efficacy endpoints included
IRC-assessed response rate (defined as ORR, complete response [CR]
plus complete response with incomplete marrow recovery [CRi],
nodular partial response [nPR], or partial response [PR])
and overall survival (OS).1
The most common ARs (≥20 percent) of any grade for VENCLEXTA in
combination with rituximab were neutropenia (65 percent), diarrhea
(40 percent), upper respiratory tract infection (39 percent),
fatigue (22 percent), cough (22 percent), and nausea (21 percent).
In the VENCLEXTA plus rituximab arm, discontinuations due to any
ARs occurred in 16 percent of patients, dose reduction in 15
percent, and dose interruption in 71 percent. In the bendamustine
plus rituximab arm, ARs led to treatment discontinuation in 10
percent of patients, dose reduction in 15 percent, and dose
interruption in 40 percent. In the VENCLEXTA in combination
with rituximab arm, neutropenia led to dose interruption of
VENCLEXTA in 46 percent of patients and discontinuations in 3
percent, and thrombocytopenia led to discontinuation in 3 percent
of patients. In the VENCLEXTA in combination with rituximab arm,
fatal ARs that occurred in the absence of disease progression and
within 30 days of the last VENCLEXTA treatment and/or 90 days of
last rituximab were reported in 2 percent (4/194) of patients.
Serious ARs were reported in 46 percent of patients, with the most
frequent (≥5 percent) being pneumonia (9 percent).1
About the Monotherapy Studies
M13-982 (NCT01889186) was a multicenter, open-label, single-arm
clinical trial of 106 patients with CLL with 17p deletion who had
received at least one prior therapy. The efficacy of VENCLEXTA
was evaluated by ORR as assessed by an IRC using the International
Workshop for Chronic Lymphocytic Leukemia (iwCLL) updated National
Cancer Institute-sponsored Working Group (NCI-WG) guidelines
(2008). The median time on treatment at the time of evaluation was
12.1 months (range: 0 to 21.5 months). Results showed the ORR was
80 percent (95% CI: 71, 87). The CR and CRi rates were 6 percent
and 2 percent, respectively; and the nPR and PR rates were 3
percent and 70 percent. Time to first response (TTFR), duration of
response (DOR), and MRD-negativity were also
evaluated.1
M12-175 (NCT01328626) was a multicenter, open-label study that
enrolled previously treated patients with CLL or SLL, including
those with 17p deletion. Efficacy was evaluated in 67 patients (59
with CLL, 8 with SLL) according to 2008 iwCLL guidelines. The
median duration of treatment at the time of evaluation was 22.1
months (range: 0.5 to 50.1 months). As assessed by an IRC, ORR was
71 percent (95% CI: 58, 82), CR+CRi rate was 7 percent, and PR rate
was 64 percent. Based on investigator assessments, the ORR in
patients with CLL was 80 percent (14 percent CR+CRi, 66 percent
PR+nPR). For the 8 patients with SLL, the investigator assessed ORR
was 100 percent.1
M14-032 (NCT02141282) was a multicenter, open-label study that
evaluated the efficacy of VENCLEXTA in patients with CLL who had
been previously treated with and progressed on or after ibrutinib
or idelalisib. Efficacy was evaluated in 127 patients (91 with
prior ibrutinib, 36 with prior idelalisib) according to 2008 iwCLL
guidelines. At the time of analysis, the median duration of
treatment was 14.3 months (range: 0.1 to 31.4 months). Based on IRC
assessment, the ORR was 70 percent (95% CI: 61, 78), with a CR+CRi
rate of 1 percent, and a PR rate of 69 percent. Based on
investigator assessment, the ORR was 65 percent (95% CI: 56,
74).1
Safety was evaluated in a pooled dataset of 352 patients from
the three monotherapy studies. Fatal ARs were reported in 2 percent
of patients, most commonly (2 patients) from septic shock. Serious
ARs were reported in 52 percent of patients, with the most frequent
(≥5 percent) being pneumonia (9 percent), febrile neutropenia (5
percent), and sepsis (5 percent). Discontinuations due to ARs
occurred in 9 percent of patients, and dose reductions due to ARs
occurred in 13 percent of patients. The most common ARs (≥20
percent) any grade were neutropenia (50 percent), diarrhea (43
percent), nausea (42 percent), upper respiratory tract infection
(36 percent), anemia (33 percent), fatigue (32 percent),
thrombocytopenia (29 percent), musculoskeletal pain (29 percent),
edema (22 percent), and cough (22 percent). The most common Grade 3
or 4 ARs (≥5 percent) were
neutropenia (45 percent), thrombocytopenia (20 percent), anemia (18
percent), pneumonia (8 percent), lymphopenia (7 percent), and
febrile neutropenia (6 percent).1
About VENCLEXTA® (venetoclax tablets) (US)
VENCLEXTA is an oral BCL-2 inhibitor that targets a
specific protein in the body called BCL-2.1 When you
have CLL or SLL, BCL-2 may build up and prevent cancer cells from
self-destructing naturally. VENCLEXTA targets BCL-2 in order 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 with
venetoclax, which is currently being evaluated in clinical trials
in several hematologic cancers.6, 7, 8, 9
VENCLEXTA (VENCLYXTO® in the EU) is currently approved as
a monotherapy in 53 nations, including the U.S. AbbVie, in
collaboration with Roche and Genentech, is currently working with
regulatory agencies around the world to bring this medicine to
additional eligible patients in need.
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.5 The FDA approved this indication under
accelerated approval based on overall response rate.5
With this approval, VENCLEXTA is now approved for the treatment of
patients with CLL or SLL, with or without 17p deletion, who have
received at least one prior therapy in combination with rituximab
or as monotherapy. 1
VENCLEXTA has been granted four Breakthrough Therapy
Designations from the FDA including for the combination treatment
regimen of VENCLEXTA plus rituximab for patients with CLL who have
received at least one prior therapy.2 This designation
is intended to expedite the development and review of therapies for
serious or life-threatening conditions.10 The
approval of the VENCLEXTA plus rituximab treatment regimen marks
the second approval granted under priority review by the FDA for
VENCLEXTA. In January 2016, AbbVie announced that the FDA
granted priority review for the NDA application for single agent
VENCLEXTA.
What is VENCLEXTA® (venetoclax tablets)?
VENCLEXTA is
a prescription medicine used to treat people with chronic
lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with
or without 17p deletion, who have received at least one prior
treatment.
It is not known if VENCLEXTA is safe and effective in
children.
Important VENCLEXTA® (venetoclax tablets) 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 health care provider will do tests to check your risk of
getting TLS 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 health care provider
will do blood tests in your first 5 weeks of treatment to check you
for TLS during treatment with VENCLEXTA. It is important to
keep your appointments for blood tests. Tell your health care
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.
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 tumor lysis syndrome.
- 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 health care 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 health care provider tells you it is okay. If you are
not sure about the type of immunization or vaccine, ask your health
care 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 health
care 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 health care
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, 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 health care provider will do blood tests to check your
blood counts during treatment with VENCLEXTA. Tell your health care
provider right away if you have a fever or any signs of an
infection while taking VENCLEXTA.
The most common side effects of VENCLEXTA when used in
combination with rituximab include low white blood cell count,
diarrhea, upper respiratory tract infection, cough, tiredness,
and nausea.
The most common side effects of VENCLEXTA when used alone
include low white blood cell count, diarrhea,
nausea, upper respiratory tract infection, low red blood
cell count, tiredness, low platelet count, muscle and joint
pain, swelling of your arms, legs, hands, and feet, and cough.
The most common side effects of VENCLEXTA when used in
combination with rituximab include diarrhea, nausea, upper
respiratory tract infection and feeling tired.
VENCLEXTA may cause fertility problems in males. This may affect
your ability to father a child. Talk to your health care provider
if you have concerns about fertility.
These are not all the possible side effects of VENCLEXTA. Tell
your health care provider if you have any side effect that bothers
you or that does not go away.
People are encouraged to report negative side effects of
prescription drugs to the FDA. Visit www.fda.gov/medwatch or call
1-800-FDA-1088.
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.
Patient Assistance
For those who qualify, patient
assistance options are available for people taking VENCLEXTA in the
U.S. If people cannot afford their medication, they should contact
www.pparx.org for assistance.
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 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 or 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, 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," of AbbVie's 2017 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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chromosomal abnormality.
https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm495253.htm.
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(2018). NCT01994837: A Phase 2 Study of ABT-199 in subjects with
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2018.
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7 Clinicaltrials.gov
(2018). NCT01794520: Study evaluating ABT-199 in subjects with
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8 Clinicaltrials.gov
(2018). NCT01328626: A Phase 1 study evaluating the safety and
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Chronic Lymphocytic Leukemia and Non-Hodgkin Lymphoma.
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(2018). NCT01889186: A study of the efficacy of ABT-199 in subjects
with relapsed/refractory or previously untreated chronic
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10 U.S. Food and Drug
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Accessed June 2018.
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