NORTH CHICAGO, Ill.,
March 12, 2020 /PRNewswire/ -- AbbVie
(NYSE: ABBV), a research-based global biopharmaceutical company,
announced today that the European Commission (EC) has
approved VENCLYXTO® (venetoclax) in combination
with obinutuzumab for the treatment of adult patients with chronic
lymphocytic leukemia (CLL) who were previously untreated. The
approval is valid in all 27 member states of the EU, as well as
Iceland, Liechtenstein, Norway and the United Kingdom.
"This approval underscores the growing utility of VENCLYXTO in
treating CLL and demonstrates its clinical benefit as a
chemotherapy-free combination therapy option for CLL patients in
Europe who have not yet been
treated," said Neil Gallagher, M.D.,
Ph.D., chief medical officer and vice president of development. "We
look forward to bringing VENCLYXTO to even more patients who can
potentially benefit from achieving a deep response and sustained
progression free survival, with the added benefit of a finite
treatment duration."
This is the third approval for VENCLYXTO, a first-in-class
B-cell lymphoma-2 (BCL-2) inhibitor. BCL-2 is a protein that
prevents cancer cells from undergoing apoptosis, the process that
leads to the natural death or self-destruction of cancer cells.
VENCLYXTO is also approved in combination with rituximab for the
treatment of adult patients with CLL who have received at least one
prior therapy, and as a monotherapy for the treatment of CLL in the
presence or absence of 17p deletion or TP53 mutation in adult
patients who are unsuitable for or have failed a B-cell receptor
pathway inhibitor.
This most recent approval is based on results from the Phase 3
CLL14 clinical trial primary analysis (median follow up of 28
months), which demonstrated superior progression-free survival
(PFS; the time on treatment without disease progression or death)
as assessed by investigators in patients treated with VENCLYXTO
plus obinutuzumab compared to patients who received a standard of
care chemotherapy regimen of chlorambucil plus obinutuzumab (hazard
ratio 0.35; 95% CI (0.23,0.53), p<0.0001, medians not yet
reached). At an updated CLL14 efficacy analysis (median follow-up
of 40 months), the median PFS had not been reached in the
VENCLYXTO + obinutuzumab arm and was 35.6 months [95% CI:
33.7,40.7] in the obinutuzumab + chlorambucil arm (hazard ratio
0.31; 95% CI: 0.22, 0.44). The 36-month PFS estimate in the
venetoclax plus obinutuzumab arm was 81.9% [95% CI: 76.5, 87.3] and
in the obinutuzumab plus chlorambucil arm was 49.5% [95% CI: 42.4,
56.6]. Additionally, after completing one year of treatment,
patients treated with the VENCLYXTO combination experienced deep
response as measured by higher rates of undetectable minimal
residual disease (MRD) or complete response (CR) as compared to
patients receiving a standard of care
regimen.1,5
In the trial, adverse events (AEs) were consistent with the
known safety profiles of venetoclax and obinutuzumab alone. At
least one AE of any grade occurred in 94.3% of patients in the
venetoclax combination arm. The most common Grade 3/4 AEs were
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
"CLL is the most common of the nearly 95,000 new cases of
leukemia in Europe each year, and
chemotherapy is often the first line of treatment," said
Michael Hallek, M.D., lead
investigator of the CLL14 study, director of the Department of
Internal Medicine and Center of Integrated Oncology at the
University Hospital Cologne in Germany, and head of the German CLL Study
Group. "Having the option to utilize a first-line,
chemotherapy-free treatment combination that can produce a deep
response, thus allowing patients to stop treatment, will change the
way we treat CLL and have a significant impact on patients."
In January 2020, AbbVie announced that the European Committee
for Medicinal Products for Human Use (CHMP) granted a positive
opinion for the Marketing Authorization Application for
VENCLYXTO plus obinutuzumab for the treatment of patients with
previously untreated CLL.
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. In 2018, approximately
95,000 new cases of leukemia were diagnosed in Europe.2 CLL is the most common
form of leukemia in the Western Hemisphere, accounting for
approximately one third of new leukemia
diagnoses.3,4
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.
VENCLYXTO (venetoclax) EU Indication and Summary of Important
Safety Information5
Indication
Venclyxto in combination with obinutuzumab
is indicated for the treatment of adult patients with previously
untreated chronic lymphocytic leukaemia (CLL).
Venclyxto in combination with rituximab is indicated for the
treatment of adult patients with 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. Patients require monitoring of signs and symptoms of
infection and prompt treatment. 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 studies with obinutuzumab or 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 obinutuzumab or
rituximab were pneumonia, sepsis 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 venetoclax in combination with obinutuzumab
or rituximab in the CLL14 and MURANO studies, respectively.
In the monotherapy studies with venetoclax, 11% of patients
discontinued due to adverse reactions.
Dosage reductions due to adverse reactions occurred in 21% of
patients treated with the combination of venetoclax and
obinutuzumab in the CLL14 study, 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 International Agency for Research on Cancer. World
Health Organization. Europe Globocan 2018.
https://gco.iarc.fr/today/data/factsheets/populations/908-europe-fact-sheets.pdf.
Accessed February 2020.
3 NCI dictionary. NCI Dictionary of Terms. Chronic
Lymphocytic Leukemia.
https://www.cancer.gov/publications/dictionaries/cancer-terms.
Accessed January 2020.
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 January 2020.
5 Summary of Product Characteristics for VENCLYXTO.
Ludwigshafen, Germany: AbbVie
Deutschland GmbH & Co. KG.
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