NORTH CHICAGO, Ill.,
April 23, 2021 /PRNewswire/ -- AbbVie
(NYSE: ABBV) today announced that the Committee for Medicinal
Products for Human Use (CHMP) of the European Medicines Agency
(EMA) adopted a positive opinion for VENCLYXTO® (venetoclax) in
combination with hypomethylating agents for the treatment of adult
patients with newly diagnosed acute myeloid leukemia (AML) who are
ineligible for intensive chemotherapy. The positive CHMP opinion is
a scientific recommendation for marketing authorization to the
European Commission (EC), which is expected to deliver its final
decision on VENCLYXTO combination therapy for use in AML in the
first half of 2021.
The positive CHMP opinion represents the third for an extension
of indications for VENCLYXTO. The opinion is based on results from
the double-blind, placebo-controlled VIALE-A (M15-656) and the
Phase 1b open-label, nonrandomized,
multicenter M14-358 trial.
"This positive CHMP opinion for VENCLYXTO in acute myeloid
leukemia is a critical step to providing new therapeutic options in
the European Union for patients with this devastating disease,"
said Mohamed Zaki, M.D., Ph.D., vice
president and global head of oncology development at AbbVie.
"Enabling improved outcomes including potentially prolonging the
lives of patients with malignant diseases such as acute myeloid
leukemia is part of our mission and an objective we pursue
relentlessly every day."
AML is the most common acute leukemia in the
world.1 An estimated 160,000 people are currently
living with the disease globally. 1 The rate of new
cases of acute myeloid leukemia is 4.3 per 100,000 men and women
per year.3 It is also among the most difficult
blood cancers to treat.2 Despite advances in
available therapies and care, the five-year survival rate for
patients diagnosed with AML remains approximately 29
percent.3 AML typically worsens quickly, and due to
age and comorbidities, not all patients can tolerate intensive
chemotherapy.4
"AML is an incredibly aggressive form of cancer, and patients
who are diagnosed with this disease are often so ill that they
cannot tolerate the intensive chemotherapy that healthcare
providers would typically prescribe," said Hartmut Döhner, M.D.,
Professor of Medicine and Director, Department of Hematology,
Oncology, Palliative Care, Rheumatology and Infectious Diseases at
University Hospital in Ulm, Germany. "VENCLYXTO combination therapy is a
promising advancement for patients and their healthcare providers
facing this challenging, lethal form of cancer."
Venetoclax 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 VENCLYXTO AML Clinical Trial Program
AbbVie's clinical trial program to evaluate VENCLYXTO combination
therapy in patients with newly diagnosed acute myeloid leukemia
(AML) who were ineligible for intensive chemotherapy included two
studies conducted around the world.
VIALE-A (M15-656) Phase 3 Trial
The
randomized, double-blind, placebo-controlled VIALE-A (M15-656)
trial evaluated the efficacy and safety of VENCLYXTO in combination
with azacitidine in patients with newly diagnosed AML who were
ineligible for intensive chemotherapy. The study met its primary
endpoints of statistically significant improvement of overall
survival (OS) and complete remission rate and complete remission
with incomplete hematologic recovery (CR + CRi). OS was 14.7 months
for the VENCLYXTO plus azacitidine arm versus 9.6 months in the
placebo plus azacitidine arm. The study also met secondary
endpoints, with the VENCLYXTO plus azacitidine arm resulting in a
CR rate of 36.7 percent vs. 17.9 percent in the placebo plus
azacitidine arm and a composite complete remission rate (CR + CRi)
of 66.4 percent versus 28.3 percent. The safety profile of
VENCLYXTO plus azacitidine was consistent with the known
side-effect profiles of both agents, and adverse events (AEs) were
consistent with expectations for an older AML population; no
differences between the two treatment arms with respect to
quality-of-life measures were seen. The most frequently reported
serious AEs in the VENCLYXTO plus azacitidine arm and placebo plus
azacitidine arm were febrile neutropenia (in 30 percent and 10
percent), pneumonia (in 17 percent and 22 percent), sepsis (in 6
percent and 8 percent), and haemorrhage (in 9 percent and 6
percent).5
M14-358 Phase 1b
Trial
The non-randomized, open-label M14-358 trial
evaluated VENCLYXTO in combination with azacitidine or decitabine
in patients with newly diagnosed AML. The trial showed patients
treated with VENCLYXTO in combination with azacitidine achieved a
CR rate of 44 percent and a CR+CRi rate of 71 percent. The median
duration of response for patients treated with VENCLYXTO in
combination with azacitidine who achieve a CR or CRi was 21.9
months. Median time to first CR or CRi was 1.2 months (range: 0.7
to 7.7 months). Patients who received VENCLYXTO in combination with
decitabine achieved a CR rate of 55 percent and a CR+CRi rate of 74
percent. The median duration of response for patients treated with
VENCLYXTO in combination with decitabine who achieved a CR or CRi
was 15 months. Median time to first CR or CRi was 1.9 months
(range: 0.9 to 5.4 months). The most frequently reported serious
AEs in patients receiving VENCLYXTO in combination with azacitidine
were febrile neutropenia (31 percent) and pneumonia (26 percent).
The most frequently reported serious AEs in patients receiving
VENCLYXTO in combination with decitabine were febrile neutropenia
(42 percent), pneumonia (29 percent), bacteraemia (16 percent) and
sepsis (6 percent).6
About VENCLYXTO® (venetoclax)
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. VENCLYXTO targets the BCL-2 protein and works to help
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. Venetoclax is approved in more than 80 countries,
including the U.S.
Indication and Important VENCLYXTO (venetoclax) EU Safety
Information7
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
TLS, including fatal events, has occurred in patients with CLL
when treated with VENCLYXTO.
Patients should be assessed for risk and should receive
appropriate prophylaxis, monitoring, and management for
TLS. The risk of TLS is a continuum based on multiple
factors, including comorbidities. 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.
Neutropenia (grade 3 or 4) has been reported and complete blood
counts should be monitored throughout the treatment
period.
Serious infections including sepsis with fatal outcome have been
reported. Monitoring of any signs and symptoms of infection is
required. Suspected infections should receive prompt
treatment including antimicrobials and dose interruption or
reduction as appropriate.
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: moderate or strong
CYP3A inhibitors must be used, physicians should refer to the
VENCLYXTO summary of product characteristics (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.
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 occurring 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 CLL14, in 15% of patients treated with the
combination of venetoclax and rituximab in Murano, and in 14% of
patients treated with venetoclax in the monotherapy
studies. The most common adverse reaction that
led to dose interruptions was neutropenia.
Specific Populations
Patients with reduced renal function (CrCl <80 mL/min) may
require more intensive prophylaxis and monitoring to reduce the
risk of TLS at initiation and during the dose-titration
phase. 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.
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 nursing women to discontinue breastfeeding
during treatment.
This is not a complete summary of all safety information. See
VENCLYXTO (venetoclax) 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 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, 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 2020 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 Puty, T.C., Sarraf, J.S., Do Carmo Almeida,
T.C. et al. Evaluation of the impact of single-nucleotide
polymorphisms on treatment response, survival and toxicity with
cytarabine and anthracyclines in patients with acute myeloid
leukaemia: a systematic review protocol. Syst Rev 8, 109
(2019).
2 American Cancer Society (2018). Typical Treatment
of Most Types of Acute Myeloid Leukemia (Except Acute Promyelocytic
M3). https://www.cancer.org/cancer/acute-myeloid-leukemia/treating/typical-treatment-of-aml.html.
3 National Cancer Institute (2018). Acute Myeloid
Leukemia - SEER Stat Fact
Sheets. https://seer.cancer.gov/statfacts/html/amyl.html.
4 Pettit, K and Odenike, O. Defining and Treating
Older Adults with Acute Myeloid Leukemia Who Are Ineligible for
Intensive Therapies. Front Oncol. 2015; 5:250.
5 DiNardo, C.D., Jonas, B.A., et al. A Randomized,
Double-Blind, Placebo-Controlled Study of Venetoclax With
Azacitidine Vs. Azacitidine In Treatment-Naïve Patients with Acute
Myeloid Leukemia Ineligible For Intensive Therapy: The Phase 3
VIALE-A Trial. (2020).
6 DiNardo CD, et al. Safety and preliminary efficacy of
venetoclax with decitabine or azacitidine in elderly patients with
previously untreated acute myeloid leukaemia: a non-randomised,
open-label, phase 1b study. Lancet
Oncol. 2018; 19(2):216-228.
7 Summary of Product Characteristics for VENCLYXTO
(venetoclax). Ludwigshafen, Germany: AbbVie Deutschland GmbH
& Co. KG.
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