NORTH CHICAGO, Ill.,
Jan. 31, 2020 /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) in combination with
obinutuzumab for the treatment of patients with chronic lymphocytic
leukemia (CLL) who were previously untreated. The positive CHMP
opinion is a scientific recommendation for marketing authorization
to the European Commission (EC), which is expected to deliver its
final decision in the first half of 2020.
"The positive CHMP opinion for this new indication in chronic
lymphocytic leukemia is an important step forward for patients and
underscores the growing utility of VENCLYXTO in treating this
common blood cancer," said Neil
Gallagher, M.D., Ph.D., chief medical officer and vice
president of development. "If approved by the EC, the venetoclax
and obinutuzumab combination would be the first chemotherapy-free
option for treatment-naïve patients with chronic lymphocytic
leukemia where dosing can be completed in one year."
The CHMP positive opinion is based on results from the Phase 3
CLL14 clinical trial, which evaluated the efficacy and safety of
VENCLYXTO in combination with obinutuzumab compared with
chlorambucil in combination with obinutuzumab. The primary endpoint
was progression-free survival (PFS; the time on treatment without
disease progression or death) as assessed by an investigator. At
the time of analysis, investigator-assessed results demonstrated
that patients treated with VENCLYXTO plus obinutuzumab achieved
superior PFS compared to patients treated with obinutuzumab plus
chlorambucil. Adverse events were consistent with the known safety
profiles of venetoclax and obinutuzumab alone. At least one AE of
any grade occurred in 94.3 percent of patients in the venetoclax
combination arm, with the most common Grade 3/4 AEs in patients
being febrile neutropenia and infections. Tumor lysis syndrome
(TLS) was reported in three patients in the venetoclax plus
obinutuzumab group (all during treatment with obinutuzumab and
before venetoclax).1 Results from the CLL14 trial
were presented at the 2019 American Society of Clinical Oncology
(ASCO) Annual Meeting and published in the New England Journal
of Medicine.
"Chemotherapy has historically been the first treatment for
patients with chronic lymphocytic leukemia. If the venetoclax plus
obinutuzumab combination is approved in the EU,
previously-untreated patients will, for the first time, have a
chemotherapy-free, fixed-duration treatment option," said
Michael Hallek, M.D., lead
investigator of the CLL14 study, Director of the Department of
Internal Medicine and Center of Integrated Oncology Cologne-Bonn at
the University Hospital Cologne in Germany, and Head of the German CLL Study
Group. "The early use of venetoclax plus obinutuzumab combination
has the potential to change the treatment paradigm for chronic
lymphocytic leukemia as it has been demonstrated to improve
outcomes, allowing patients to live longer without disease
progression."
In 2018, the EC approved VENCLYXTO plus rituximab for the
treatment of patients with relapsed or refractory (R/R) CLL.
VENCLYXTO monotherapy was previously approved in the EU for 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.
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 Chronic Lymphocytic Leukemia
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. CLL is the most
common form of leukemia in the Western Hemisphere, accounting for
approximately one third of new leukemia
diagnoses.2,3
About the CLL14 Trial
The randomized, multicenter, open-label, actively controlled 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 VENCLYXTO and obinutuzumab (n=216) versus
obinutuzumab and chlorambucil (n=216) in patients with
previously-untreated 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 cycles for VENCLYXTO in combination with six
cycles of obinutuzumab. Cycles were comprised of 28 days. The trial
enrolled 432 patients, all of whom were diagnosed according to the
International Workshop on Chronic Lymphocytic Leukemia (iwCLL)
criteria and were previously untreated. The primary efficacy
outcome was PFS as assessed by the
investigator.1
Key secondary endpoints were MRD negativity in peripheral blood
and bone marrow, and overall and complete response
rates.1
About VENCLYXTO® (venetoclax
tablets)
VENCLYXTO® 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. VENCLYXTO
targets the BCL-2 protein and works to restore the process of
apoptosis.
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.
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) EU Indication and Safety
Information4
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
Tumour lysis syndrome (TLS), including fatal events, has occurred
in patients with previously treated CLL with high tumour 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.
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, diarrhoea, and upper respiratory tract
infection. In the monotherapy studies, the most common adverse
reactions were neutropenia/neutrophil count decreased, diarrhoea,
nausea, anaemia, fatigue, and upper respiratory tract
infection.
The most frequently reported serious adverse reactions (≥2%) in
patients receiving venetoclax in combination with rituximab were
pneumonia, febrile neutropenia, and TLS. In the monotherapy
studies, the most frequently reported serious adverse reactions
(≥2%) were pneumonia and febrile neutropenia.
Discontinuations due to adverse reactions occurred in 16% of
patients treated with the combination of venetoclax and rituximab
in the MURANO study. In the monotherapy studies with venetoclax,
11% of patients discontinued due to adverse reactions.
Dosage reductions due to adverse reactions occurred in 15% of
patients treated with the combination of venetoclax and rituximab
in the MURANO study and 14% of patients treated with venetoclax in
the monotherapy studies.
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.
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 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. 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 2019 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 Fischer K, et al. Effect of fixed-duration
venetoclax plus obinutuzumab (VenG) on progression-free survival
(PFS), and rates and duration of minimal residual disease
negativity (MRD–) in previously untreated patients (pts) with
chronic lymphocytic leukemia (CLL) and comorbidities. Presented at
the 2019 American Society of Clinical Oncology Annual Meeting:
June 4, 2019; Chicago.
2 NCI dictionary. NCI Dictionary of Terms. Chronic
Lymphocytic Leukemia.
https://www.cancer.gov/publications/dictionaries/cancer-terms.
Accessed January 2020.
3 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 January 2020.
4 Summary of Product Characteristics for VENCLYXTO.
Ludwigshafen, Germany: AbbVie
Deutschland GmbH & Co. KG.
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