NORTH CHICAGO, Ill.,
Sept. 21, 2018 /PRNewswire/
-- AbbVie (NYSE: ABBV), a research-based global
biopharmaceutical company, announced today that the Committee for
Medicinal Products for Human Use (CHMP) of the European Medicines
Agency (EMA) has granted a positive opinion
for VENCLYXTO® (venetoclax tablets) in combination
with rituximab for the treatment of patients with
relapsed/refractory chronic lymphocytic leukemia (R/R CLL) who have
received at least one prior therapy. The positive CHMP opinion is a
scientific recommendation for marketing authorization to the
European Commission (EC), which will deliver its final decision,
valid in all 28 member states of the European Union, as well as
Iceland, Liechtenstein and Norway.
In 2016, VENCLYXTO was approved by the EC as a monotherapy for
the treatment of R/R 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. If approved by the EC, VENCLYXTO plus rituximab could be
prescribed to a broader patient population with R/R CLL than the
currently approved indication for VENCLYXTO monotherapy in the
EU.
"This positive CHMP opinion is one important step forward as
AbbVie continues to further the research and development of novel
medicines with the potential to transform the standard of care in
blood cancers," said Michael
Severino, M.D., executive vice president, research and
development and chief scientific officer, AbbVie. "The combination
of VENCLYXTO with rituximab has the potential to give patients with
relapsed/refractory chronic lymphocytic leukemia a chance to live
longer without their disease progressing, and to stop treatment
after their two-year course."
The CHMP positive opinion is based on results from the MURANO
Phase 3 clinical trial, which evaluated the efficacy and safety of
VENCLYXTO in combination with rituximab compared with bendamustine
in combination with rituximab. At the time of the primary analysis,
the trial demonstrated a statistically significant improvement in
investigator-assessed progression-free survival (PFS; the time on
treatment without disease progression or death2) for
patients who received VENCLYXTO plus rituximab compared with
bendamustine plus rituximab.1
In the MURANO clinical trial, undetectable minimal residual
disease (uMRD), also known as minimal residual disease negativity
(MRD-) was a secondary endpoint assessed at the end of combination
therapy (nine-month assessment). The majority of patients
in the trial who received VENCLYXTO plus rituximab achieved uMRD in
the peripheral blood.1 Undetectable minimal residual
disease, 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.2
"The venetoclax plus rituximab combination has the potential to
be truly transformative for patients with relapsed/refractory CLL,"
said Prof. John Seymour, MBBS,
Ph.D., lead investigator of the MURANO trial and Director of Cancer
Medicine at the Peter MacCallum Cancer Centre & Royal Melbourne
Hospital in Australia. "The
progression-free survival observed in the MURANO trial, and the
fixed duration of treatment that may allow patients to stop
treatment, are encouraging developments with the potential to
advance the care and management of patients with
relapsed/refractory CLL."
CLL is a slow-growing form of leukemia, or blood cancer, in
which too many immature lymphocytes (a type of white blood cell)
are found predominantly in the blood and bone marrow.3
CLL accounts for approximately one third of new leukemia
diagnoses.4
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.
About the 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 VENCLYXTO 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: 22-85).1
The primary efficacy endpoint was investigator (INV)-assessed
PFS. 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), overall survival, and rates of
uMRD.1
About VENCLYXTO® (venetoclax
tablets)
VENCLEXTA® (VENCLYXTO® in the EU) is a
first-in-class medicine that selectively binds and inhibits the
B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other
cancerous tumors, BCL-2 builds up and prevents cancer cells from
undergoing their natural death or self-destruction process, which
is called apoptosis. VENCLEXTA targets the BCL-2 protein and works
to 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 and Roche are currently working with
regulatory agencies around the world to bring this medicine to
additional eligible patients in need.
Important VENCLYXTO (venetoclax tablets) EU Safety
Information5
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 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.
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.
Coadministration 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
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 females of reproductive potential to avoid
pregnancy during treatment. 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, 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.
1 Seymour 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.
2 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.
3 NCI dictionary. NCI Dictionary of Terms. Chronic
Lymphocytic Leukemia.
https://www.cancer.gov/publications/dictionaries/cancer-terms.
Accessed September 2018.
4 World Health Organization. 2014 Review of Cancer
Medicines on the WHO List of Essential Medicines.
http://www.who.int/selection_medicines/committees/expert/20/applications/CLL.pdf.
Accessed September 2018.
5 Summary of Product Characteristics for VENCLYXTO.
Ludwigshafen, Germany: AbbVie
Deutschland GmbH & Co. KG.
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