Presentations support CALQUENCE efficacy and
tolerability with long-term follow-up in mantle cell lymphoma and
pooled safety data in chronic lymphocytic leukemia
Emerging pipeline shows promise in novel
targets and mechanisms to treat resistant and aggressive blood
cancers
AstraZeneca will present new research aimed at addressing key
unmet needs facing patients with blood cancers at the 62nd American
Society of Hematology (ASH) Annual Meeting and Exposition, held
virtually from 5 to 8 December 2020.
The Company will present 27 abstracts spanning five medicines
and potential new medicines and eight different hematology
conditions that demonstrate the Company’s commitment to advancing
hematology research and treatments for patients living with
hematologic malignancies.
Key data presentations include:
- A pooled analysis of data from four trials – ELEVATE TN,
ASCEND, ACE-CL-001 and 15-H-0016 – expanding on the cardiovascular
safety profile of CALQUENCE (acalabrutinib) monotherapy treatment
for patients with chronic lymphocytic leukemia (CLL)
- Extended follow-up data from the pivotal Phase II ACE-LY-004
trial that support long-term treatment with CALQUENCE in adult
patients with relapsed or refractory mantle cell lymphoma
(MCL)
- Data on CALQUENCE in combination with venetoclax and either
obinutuzumab or rituximab in patients with CLL, showing a safety
profile consistent with previous trials with high complete
responses and undetectable minimal residual disease rates after a
median follow-up of 26.9 months, with minimal to no drug-drug
interactions in the Phase Ib ACE-CL-003 trial
- First-in-human data from the potential new medicine B-cell
maturation antigen (BCMA)-targeted antibody drug conjugate,
MEDI2228, presenting data on safety and efficacy at all dose levels
in relapsed or refractory multiple myeloma
- Data showing pre-clinical evidence of overcoming resistance in
relapsed or refractory MCL from the dual BCL2/XL inhibitor,
AZD4320, which blocks the anti-apoptotic effect of BCL2 and
BCLXL
- Phase I data from the anti-inducible co-stimulator anti-ICOS
monoclonal antibody, MEDI-570, demonstrating promising early
clinical activity in poor-risk refractory and heavily pretreated
patients with angioimmunoblastic T-cell lymphoma
- Multiple studies on roxadustat, the first in a new class of
medicines evaluating its clinical effectiveness and safety profile
in both the dialysis dependent and non-dialysis dependent anemia of
CKD patient populations
- Data on roxadustat assessing efficacy in anemia secondary to
lower-risk myelodysplastic syndrome (MDS) regardless of baseline
factors. In approximately one in three patients MDS leads to acute
myeloid leukemia1
Dave Fredrickson, Executive Vice President, Oncology Business
Unit, said: “Our data at ASH this year continue to support
CALQUENCE as a well-tolerated treatment with impressive efficacy
and safety across multiple blood cancers, reinforcing physicians’
confidence in treating patients with CALQUENCE over the long term.
Data at the meeting will also explore CALQUENCE combinations with
commonly used therapies, showing potential across a variety of
regimens in chronic lymphocytic leukemia to best suit the unique
needs of each patient.”
José Baselga, Executive Vice President, Oncology R&D, said:
“As we rapidly expand our presence in hematology, we are focused on
identifying novel targets and mechanisms of action that can address
the most urgent unmet needs across various hematological
malignancies. Our early portfolio at this year’s ASH clearly
demonstrates our commitment to following the science in combating
treatment-resistant and rare blood cancers.”
Key AstraZeneca presentations during
the 62nd ASH Annual Meeting and Exposition
Lead author
Abstract title
Presentation details
CALQUENCE (acalabrutinib)
Brown, JR
Pooled Analysis of Cardiovascular Events
from Clinical Trials Evaluating Acalabrutinib Monotherapy in
Patients with CLL
Abstract #3146
Oral and Poster Abstracts
Monday, 7 December
7am–3:30pm PST
Wang, M
Acalabrutinib Monotherapy in Patients with
Relapsed/Refractory MCL: Long-Term Efficacy and Safety Results from
a Phase 2 Study
Abstract #2040
Oral and Poster Abstracts Mantle Cell,
Follicular, and Other Indolent B-Cell Lymphoma Sunday, 6
December
7am– 3:30pm PST
Woyach, JA
Acalabrutinib in Combination with
Venetoclax and Obinutuzumab or Rituximab in Patients with
Treatment-Naïve or Relapsed/Refractory CLL
Abstract #1312
Oral and Poster Abstracts CLL: Therapy,
excluding Transplantation
Saturday, 5 December 7am – 3:30pm PST
Davids, MS
Updated Safety and Efficacy Results from a
Phase 2 Study of Acalabrutinib, Venetoclax and Obinutuzumab for
Frontline Treatment of CLL
Abstract #3141
Oral and Poster Abstracts CLL: Therapy,
excluding Transplantation
Monday, 7 December 7am – 3:30pm PST
Munir, T
Cost-effectiveness of Acalabrutinib
Monotherapy Compared with Chlorambucil Plus Obinutuzumab for
Previously Untreated CLL
Abstract #2510
Oral and Poster Abstracts Health Services
Research—Malignant Conditions
Sunday, 6 December 7am – 3:30pm PST
Roxadustat
Henry, D
Oral Roxadustat Efficacy in Anemia
Secondary to Lower-risk MDS Irrespective of Ring Sideroblasts and
Baseline Erythropoietin Levels
Abstract #1277
Oral and Poster Abstracts MDS — Clinical
Studies
Saturday, 5 December 7am – 3:30pm PST
Provenzano, R
Pooled Efficacy and Cardiovascular
Analysis of Roxadustat Compared with Placebo in Anemia Correction
in Chronic Kidney Disease Patients Not on Dialysis
Abstract #1671
Oral and Poster Abstracts Red Cells and
Erythropoiesis, Structure and Function, Metabolism, and Survival,
Excluding Iron Sunday, 6 December 7am – 3:30pm PST
Fishbane, S
Pooled Efficacy and Cardiovascular Safety
Results of Roxadustat Compared with Epoetin Alfa in the Treatment
of Anemia in Chronic Kidney Disease Patients on Dialysis
Abstract #749
Oral and Poster Abstracts Red Cells and
Erythropoiesis, Structure and Function, Metabolism, and Survival,
Excluding Iron Saturday, 5 December 7am – 3:30pm PST
Early Stage Pipeline
Kumar, S
Phase 1, First-in-Human Study of MEDI2228,
a BCMA-Targeted ADC in Patients with Relapsed/Refractory Multiple
Myeloma
Abstract #179
Oral and Poster Abstracts
Myeloma/Amyloidosis: Therapy, excluding Transplantation Saturday, 5
December 12–1:30pm PST
Li, Y
AZD4320 is a Novel and Potent BCL-2/XL
Dual Inhibitor in Targeting Aggressive MCL
Abstract #2094
Oral and Poster Abstracts Lymphoma:
Pre-Clinical—Chemotherapy and Biologic Agents Sunday, 6 December
7am – 3:30pm PST
Chavez, J
A Phase I Study of Anti-ICOS Antibody
MEDI-570 for Relapsed/Refractory (R/R) Peripheral T-cell Lymphoma
(PTCL) and Angioimmunoblastic T-cell Lymphoma (AITL) (NCI-9930)
Abstract #1151
Oral and Poster Abstracts Hodgkin Lymphoma
and T/NK Cell Lymphoma Saturday, 5 December 7am – 3:30pm PST
INDICATION AND USAGE
CALQUENCE is a Bruton tyrosine kinase (BTK) inhibitor indicated
for the treatment of adult patients with mantle cell lymphoma (MCL)
who have received at least one prior therapy.
This indication is approved under accelerated approval based on
overall response rate. Continued approval for this indication may
be contingent upon verification and description of clinical benefit
in confirmatory trials.
CALQUENCE is also indicated for the treatment of adult patients
with chronic lymphocytic leukemia (CLL) or small lymphocytic
lymphoma (SLL).
IMPORTANT SAFETY INFORMATION ABOUT CALQUENCE® (acalabrutinib)
capsules
Serious and Opportunistic Infections
Fatal and serious infections, including opportunistic
infections, have occurred in patients with hematologic malignancies
treated with CALQUENCE.
Serious or Grade 3 or higher infections (bacterial, viral, or
fungal) occurred in 19% of 1029 patients exposed to CALQUENCE in
clinical trials, most often due to respiratory tract infections
(11% of all patients, including pneumonia in 6%). These infections
predominantly occurred in the absence of Grade 3 or 4 neutropenia,
with neutropenic infection reported in 1.9% of all patients.
Opportunistic infections in recipients of CALQUENCE have included,
but are not limited to, hepatitis B virus reactivation, fungal
pneumonia, Pneumocystis jiroveci pneumonia, Epstein-Barr virus
reactivation, cytomegalovirus, and progressive multifocal
leukoencephalopathy (PML). Consider prophylaxis in patients who are
at increased risk for opportunistic infections. Monitor patients
for signs and symptoms of infection and treat promptly.
Hemorrhage
Fatal and serious hemorrhagic events have occurred in patients
with hematologic malignancies treated with CALQUENCE. Major
hemorrhage (serious or Grade 3 or higher bleeding or any central
nervous system bleeding) occurred in 3.0% of patients, with fatal
hemorrhage occurring in 0.1% of 1029 patients exposed to CALQUENCE
in clinical trials. Bleeding events of any grade, excluding
bruising and petechiae, occurred in 22% of patients.
Use of antithrombotic agents concomitantly with CALQUENCE may
further increase the risk of hemorrhage. In clinical trials, major
hemorrhage occurred in 2.7% of patients taking CALQUENCE without
antithrombotic agents and 3.6% of patients taking CALQUENCE with
antithrombotic agents. Consider the risks and benefits of
antithrombotic agents when co-administered with CALQUENCE. Monitor
patients for signs of bleeding.
Consider the benefit-risk of withholding CALQUENCE for 3-7 days
pre- and post-surgery depending upon the type of surgery and the
risk of bleeding.
Cytopenias
Grade 3 or 4 cytopenias, including neutropenia (23%), anemia
(8%), thrombocytopenia (7%), and lymphopenia (7%), developed in
patients with hematologic malignancies treated with CALQUENCE.
Grade 4 neutropenia developed in 12% of patients. Monitor complete
blood counts regularly during treatment. Interrupt treatment,
reduce the dose, or discontinue treatment as warranted.
Second Primary Malignancies
Second primary malignancies, including skin cancers and other
solid tumors, occurred in 12% of 1029 patients exposed to CALQUENCE
in clinical trials. The most frequent second primary malignancy was
skin cancer, reported in 6% of patients. Monitor patients for skin
cancers and advise protection from sun exposure.
Atrial Fibrillation and Flutter
Grade 3 atrial fibrillation or flutter occurred in 1.1% of 1029
patients treated with CALQUENCE, with all grades of atrial
fibrillation or flutter reported in 4.1% of all patients. The risk
may be increased in patients with cardiac risk factors,
hypertension, previous arrhythmias, and acute infection. Monitor
for symptoms of arrhythmia (e.g., palpitations, dizziness, syncope,
dyspnea) and manage as appropriate.
ADVERSE REACTIONS
The most common adverse reactions (≥ 20%) of any grade in
patients with relapsed or refractory MCL were anemia,*
thrombocytopenia,* headache (39%), neutropenia,* diarrhea (31%),
fatigue (28%), myalgia (21%), and bruising (21%). The most common
Grade ≥ 3 non-hematological adverse reaction (reported in at least
2% of patients) was diarrhea (3.2%).
*Treatment-emergent decreases (all grades) of hemoglobin (46%),
platelets (44%), and neutrophils (36%) were based on laboratory
measurements and adverse reactions.
Dose reductions or discontinuations due to any adverse reaction
were reported in 1.6% and 6.5% of patients, respectively. Increases
in creatinine 1.5 to 3 times the upper limit of normal occurred in
4.8% of patients.
The most common adverse reactions (≥ 30%) of any grade in
patients with CLL were anemia,* neutropenia,* thrombocytopenia,*
headache, upper respiratory tract infection, and diarrhea.
*Treatment-emergent decreases (all grades) of hemoglobin,
platelets, and neutrophils were based on laboratory measurements
and adverse reactions.
In patients with previously untreated CLL exposed to CALQUENCE,
fatal adverse reactions that occurred in the absence of disease
progression and with onset within 30 days of the last study
treatment were reported in 2% for each treatment arm, most often
from infection. Serious adverse reactions were reported in 39% of
patients in the CALQUENCE plus obinutuzumab arm and 32% in the
CALQUENCE monotherapy arm, most often due to events of pneumonia
(7% and 2.8%, respectively).
Adverse reactions led to CALQUENCE dose reduction in 7% and 4%
of patients in the CALQUENCE plus obinutuzumab arm (N=178) and
CALQUENCE monotherapy arm (N=179), respectively. Adverse events led
to discontinuation in 11% and 10% of patients, respectively.
Increases in creatinine 1.5 to 3 times the upper limit of normal
occurred in 3.9% and 2.8% of patients in the CALQUENCE combination
arm and monotherapy arm, respectively.
In patients with relapsed/refractory CLL exposed to CALQUENCE,
serious adverse reactions occurred in 29% of patients. Serious
adverse reactions in > 5% of patients who received CALQUENCE
included lower respiratory tract infection (6%). Fatal adverse
reactions within 30 days of the last dose of CALQUENCE occurred in
2.6% of patients, including from second primary malignancies and
infection.
Adverse reactions led to CALQUENCE dose reduction in 3.9% of
patients (N=154), dose interruptions in 34% of patients, most often
due to respiratory tract infections followed by neutropenia, and
discontinuation in 10% of patients, most frequently due to second
primary malignancies followed by infection. Increases in creatinine
1.5 to 3 times the upper limit of normal occurred in 1.3% of
patients who received CALQUENCE.
DRUG INTERACTIONS
Strong CYP3A Inhibitors: Avoid co-administration with a
strong CYP3A inhibitor. If a strong CYP3A inhibitor will be used
short-term, interrupt CALQUENCE.
Moderate CYP3A Inhibitors: When CALQUENCE is
co-administered with a moderate CYP3A inhibitor, reduce CALQUENCE
dose to 100 mg once daily.
Strong CYP3A Inducers: Avoid co-administration with a
strong CYP3A inducer. If a strong CYP3A inducer cannot be avoided,
increase the CALQUENCE dose to 200 mg approximately every 12
hours.
Gastric Acid Reducing Agents: If treatment with a gastric
acid reducing agent is required, consider using an H2-receptor
antagonist or an antacid. Take CALQUENCE 2 hours before taking an
H2-receptor antagonist. Separate dosing with an antacid by at least
2 hours.
Avoid co-administration with proton pump inhibitors. Due to the
long-lasting effect of proton pump inhibitors, separation of doses
may not eliminate the interaction with CALQUENCE.
SPECIFIC POPULATIONS
Based on findings in animals, CALQUENCE may cause fetal harm and
dystocia when administered to a pregnant woman. There are no
available data in pregnant women to inform the drug-associated
risk. Advise pregnant women of the potential risk to a fetus.
Pregnancy testing is recommended for females of reproductive
potential prior to initiating CALQUENCE therapy. Advise female
patients of reproductive potential to use effective contraception
during treatment with CALQUENCE and for at least 1 week following
the last dose of CALQUENCE.
It is not known if CALQUENCE is present in human milk. Advise
lactating women not to breastfeed while taking CALQUENCE and for at
least 2 weeks after the final dose.
Avoid administration of CALQUENCE in patients with severe
hepatic impairment. Dose modifications are not required for
patients with mild or moderate hepatic impairment.
Please see full Prescribing Information, including Patient
Information.
CALQUENCE CALQUENCE (acalabrutinib) is a next-generation,
selective inhibitor of Bruton’s tyrosine kinase (BTK). CALQUENCE
binds covalently to BTK, thereby inhibiting its activity.2,3 In
B-cells, BTK signaling results in activation of pathways necessary
for B-cell proliferation, trafficking, chemotaxis, and
adhesion.2
As part of an extensive clinical development program,
AstraZeneca and Acerta Pharma are currently evaluating CALQUENCE in
more than 20 company-sponsored clinical trials. CALQUENCE is being
developed for the treatment of multiple B-cell blood cancers
including CLL, MCL, diffuse large B-cell lymphoma, Waldenstr�m
macroglobulinemia, follicular lymphoma, and other hematologic
malignancies.
Roxadustat Roxadustat is a first in a new class of
investigational medications that has the potential to promote
erythropoiesis through increased endogenous production of
erythropoietin; improved iron absorption, transport and
mobilization; and downregulation of hepcidin, which helps to
overcome the negative impact of inflammation on hemoglobin
synthesis and red blood cell production. The roxadustat NDA for the
treatment of anemia in CKD in both NDD and DD is under review by
the US Food and Drug Administration with a decision expected in Q4
2020. Roxadustat is also in clinical development for anemia
associated with myelodysplastic syndromes (MDS) and for
chemotherapy-induced anemia (CIA).
AstraZeneca and FibroGen Inc. (FibroGen) are collaborating on
the development and commercialization of roxadustat for the
potential treatment of anemia in the US, China and other markets in
the Americas and in Australia/New Zealand, as well as Southeast
Asia. Astellas and FibroGen are collaborating on the development
and commercialization of roxadustat for the potential treatment of
anemia in territories including Japan, Europe, the Commonwealth of
Independent States, the Middle East and South Africa.
AstraZeneca in hematology Leveraging its strength in
oncology, AstraZeneca has established hematology as one of four key
oncology disease areas of focus. The Company’s hematology franchise
includes two medicines approved by the US Food and Drug
Administration and a robust global development program for a broad
portfolio of potential blood cancer treatments. Acerta Pharma
serves as AstraZeneca’s hematology research and development arm.
AstraZeneca partners with like-minded science-led companies to
advance the discovery and development of therapies to address unmet
need.
AstraZeneca in oncology AstraZeneca has a deep-rooted
heritage in oncology and offers a quickly growing portfolio of new
medicines that has the potential to transform patients' lives and
the Company's future. With seven new medicines launched between
2014 and 2020, and a broad pipeline of small molecules and
biologics in development, the Company is committed to advance
oncology as a key growth driver for AstraZeneca focused on lung,
ovarian, breast and blood cancers.
By harnessing the power of six scientific platforms -
Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response,
Antibody Drug Conjugates, Epigenetics, and Cell Therapies - and by
championing the development of personalized combinations,
AstraZeneca has the vision to redefine cancer treatment and one day
eliminate cancer as a cause of death.
About AstraZeneca AstraZeneca is a global, science-led
biopharmaceutical company that focuses on the discovery,
development and commercialization of prescription medicines,
primarily for the treatment of diseases in three therapy areas -
Oncology, Cardiovascular, Renal & Metabolism and Respiratory.
AstraZeneca operates in over 100 countries and its innovative
medicines are used by millions of patients worldwide. For more
information, please visit www.astrazeneca-us.com and follow us on
Twitter @AstraZenecaUS.
References
- American Cancer Society. What Are Myelodysplastic Syndromes?
Available online. Accessed October 2020.
- CALQUENCE (acalabrutinib) [prescribing information].
Wilmington, DE; AstraZeneca Pharmaceuticals LP; 2019.
- Wu J, Zhang M & Liu D. Acalabrutinib (ACP-196): a selective
second-generation BTK inhibitor. J Hematol Oncol. 2016;9(21).
View source
version on businesswire.com: https://www.businesswire.com/news/home/20201119005325/en/
Media Inquiries Michele Meixell, +1 302 885 2677 Brendan
McEvoy, +1 302 885 2677
AstraZeneca (NYSE:AZN)
Historical Stock Chart
From Mar 2024 to Apr 2024
AstraZeneca (NYSE:AZN)
Historical Stock Chart
From Apr 2023 to Apr 2024