NORTH CHICAGO, Ill.,
May 25, 2021 /PRNewswire/
-- AbbVie (NYSE: ABBV) announced today that the European
Commission (EC) has approved VENCLYXTO®
(venetoclax) in combination with a hypomethylating agent,
azacitidine or decitabine, for the treatment of adult patients with
newly diagnosed acute myeloid leukemia (AML) who are ineligible for
intensive chemotherapy.1 The approval is valid in
all 27 member states of the EU, as well as Iceland, Liechtenstein, and Norway.
"VENCLYXTO has proven incremental overall survival in treating
newly diagnosed AML in patients who are ineligible for
intensive chemotherapy when treated with VENCLYXTO plus azacitidine
compared to those treated with azacitidine alone," said
Mohamed Zaki, M.D., Ph.D., vice
president and head, global oncology development, AbbVie. "We look
forward to bringing VENCLYXTO to more AML patients who can
potentially benefit from this important new treatment option in EU
countries."
This is the third extension of indications 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.1
This most recent approval is based on results from the Phase 3
double-blind, placebo-controlled VIALE-A (M15-656) and the Phase
1b open-label, nonrandomized,
multicenter M14-358 clinical trials. The VIALE-A trial demonstrated
patients who received VENCLYXTO in combination with azacitidine
showed statistically significantly greater median overall survival
(OS) than patients receiving azacitidine alone
(p<0.001).2 The Phase 1b M14-358 trial evaluating venetoclax
in combination with hypomethylating agents, azacitidine or
decitabine, exhibited an overall safety profile that was generally
consistent with the known safety profiles of venetoclax combined
with azacitidine and the two
medications alone.3
In the VIALE-A trial, the most frequently reported serious
adverse events (AEs) in the VENCLYXTO plus azacitidine arm and
placebo plus azacitidine arm were febrile neutropenia, pneumonia,
sepsis, and haemorrhage.2 In the M14-358 trial, the
most frequently reported serious AEs in patients receiving
VENCLYXTO in combination with decitabine were febrile neutropenia,
pneumonia, bacteraemia and sepsis.3
"The European Commission approval of venetoclax combination
therapy offers a new option for people facing what is often a
devastating acute myeloid leukemia diagnosis," said Zack Pemberton-Whiteley, Chair of the Acute
Leukemia Advocates Network. "This approval represents an important
advancement for the treatment of AML and offers an
option for those who are ineligible for intensive
chemotherapy."
In April 2021, AbbVie announced that the European Committee for
Medicinal Products for Human Use (CHMP) granted a positive opinion
for the Marketing Authorization Application for VENCLYXTO in
combination with hypomethylating agents for the treatment of
patients with newly diagnosed AML who are ineligible for intensive
chemotherapy.
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 Acute Myeloid Leukemia
AML is the most common
acute leukemia in the world.4 An estimated 160,000
people are currently living with the disease
globally.4 The rate of new cases of acute myeloid
leukemia is 4.3 per 100,000 men and women per
year.5 It is also among the most difficult blood
cancers to treat.6 Despite advances in available
therapies and care, the five-year survival rate for patients
diagnosed with AML remains approximately 29
percent.5 AML typically worsens quickly, and due to
age and comorbidities, not all patients can tolerate intensive
chemotherapy.7
About the VENCLYXTO AML Clinical Trial
Program
AbbVie's clinical trial program to evaluate
VENCLYXTO combination with a hypomethylating agent 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 Trial2
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 composite complete remission (complete remission
[CR]+complete remission with incomplete hematologic recovery [CRi])
(CR + CRi). Overall survival was 14.7 months for the VENCLYXTO plus
azacitidine arm versus 9.6 months in the placebo plus azacitidine
arm, and the composite complete remission rate was 66.4 percent
versus 28.3 percent, respectively. 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. 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. 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),
respectively.2
M14-358 Phase 1b
Trial3
The non-randomized, open-label M14-358 trial evaluated VENCLYXTO in
combination with azacitidine or decitabine in patients with newly
diagnosed AML who were ineligible for intensive chemotherapy.
Patients treated with VENCLYXTO in combination with decitabine
achieved a CR+CRi rate of 74 percent and a 30-day mortality rate of
6.5 percent. The median follow-up was 40.4 months (range: 0.7 to
42.7 months) for venetoclax in combination with decitabine.
The most frequently reported serious AEs (≥5%) in patients
receiving VENCLYXTO in combination with decitabine were febrile
neutropenia, pneumonia, bacteraemia and sepsis, with
neutropenia reported in 35 percent (all grades) and 35 percent
(grade 3 or 4) of patients in the venetoclax + decitabine arm. No
events of laboratory or clinical TLS were reported with venetoclax
in combination with decitabine.
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 also approved in combination with obinutuzumab for
the treatment of adult patients with previously untreated chronic
lymphocytic leukemia (CLL), 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.1
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. Venetoclax is
approved in more than 80 countries, including the U.S.
Indications and Important Venclyxto (venetoclax) EU Safety
Information1
Indications
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.
Venclyxto in combination with a hypomethylating agent is
indicated for the treatment of adult patients with newly diagnosed
acute myeloid leukaemia (AML) who are ineligible for intensive
chemotherapy.
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 tumour 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, including fatal events, has occurred in
patients when treated with Venclyxto. For CLL and AML, please refer
to the indication-specific recommendations for prevention of TLS in
the Venclyxto summary of product characteristic (SmPC).
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 at
initiation and during the 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. Complete blood
counts should be monitored throughout the treatment
period.
In patients with AML, neutropenia (grade 3 or 4) is common
before starting treatment. The neutrophil counts can worsen with
Venetoclax in combination with a hypomethylating agent. Neutropenia
can recur with subsequent cycles of therapy. Dose modification and
interruptions for cytopenias are dependent on remission status.
For CLL and AML, please refer to the indication-specific
recommendations for dose modifications for toxicities in the
Venclyxto SmPC.
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
In CLL and AML CYP3A inhibitors may increase Venclyxto plasma
concentrations.
In CLL, 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, please refer to the recommendations for
dose modifications in the Venclyxto SmPC.
In AML, please refer to the AML-specific recommendation for dose
modifications for potential interactions with CYP3A inhibitors, in
the Venclyxto SmPC.
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
CLL
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.
AML
The most commonly occurring adverse reactions (>=20%) of any
grade in patients receiving venetoclax in combination with
azacitidine or decitabine in the VIALE-A and M14-358, respectively,
were thrombocytopenia, neutropenia, febrile neutropenia, nausea,
diarrhoea, vomiting, anaemia, fatigue, pneumonia, hypokalaemia, and
decreased appetite, haemorrhage, dizziness/syncope, hypotension,
headache, abdominal pain, and anaemia.
The most frequently reported serious adverse reactions (≥5%) in
patients receiving venetoclax in combination with azacitidine were
febrile neutropenia, pneumonia, sepsis and haemorrhage. In M14-358,
the most frequently reported serious adverse reactions (≥5%) were
febrile neutropenia, pneumonia, bacteraemia and sepsis.
Discontinuations due to adverse reactions occurred in 24% of
patients treated with venetoclax in combination with azacitidine in
the VIALE-A study, and 26% of patients treated with venetoclax in
combination with decitabine in the M14-358 study, respectively.
Dosage reductions due to adverse reactions occurred in 2% of
patients in VIALE-A, and in 6 % of patients in M14-358. Venetoclax
dose interruptions due to adverse reactions occurred in 72% and 65
% of patients, respectively. The most common adverse reaction that
led to dose interruption (>10%) of Venetoclax in VIALE-A, were
febrile neutropenia, neutropenia, pneumonia, and
thrombocytopenia. The most common adverse reactions that led
to dose interruption (≥5%) of venetoclax in M14-358 were febrile
neutropenia, neutropenia/neutrophil count decreased, pneumonia,
platelet count decreased, and white blood cell count decreased.
Special 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
|
Summary of Product
Characteristics for VENCLYXTO (venetoclax). Ludwigshafen, Germany:
AbbVie Deutschland GmbH & Co. KG.
|
2
|
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).
|
3
|
DiNardo CD, et al.
Venetoclax combined with decitabine or azacitidine in
treatment-naive, elderly patients with acute myeloid leukemia.
Blood. 2019 Jan 3;133(1):7-17. doi: 10.1182/blood-2018-08-868752.
Epub 2018 Oct 25.
|
4
|
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).
|
5
|
National Cancer
Institute (2018). Acute Myeloid Leukemia - SEER Stat Fact Sheets.
https://seer.cancer.gov/statfacts/html/amyl.html. Accessed May 20,
2021
|
6
|
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.
Accessed May 20, 2021
|
7
|
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.
|
View original
content:http://www.prnewswire.com/news-releases/abbvie-receives-european-commission-approval-of-venclyxto-venetoclax-in-combination-with-a-hypomethylating-agent-for-patients-with-newly-diagnosed-acute-myeloid-leukemia-who-are-ineligible-for-intensive-chemotherapy-301298689.html
SOURCE AbbVie