TIDMAZN
RNS Number : 4350C
AstraZeneca PLC
17 June 2019
17 June 2019 07:00 BST
Calquence significantly prolonged the time patients lived
without disease progression in relapsed or refractory chronic
lymphocytic leukaemia
An encouraging 88% of patients on Calquence remained free of
disease progression after 12 months, vs. 68% of patients on
rituximab combined with idelalisib or bendamustine
AstraZeneca today announced detailed results from the interim
analysis of the Phase III ASC trial at the European Hematology
Association (EHA) Annual Congress in Amsterdam, showing Calquence
(acalabrutinib) significantly prolonged the time patients live
without disease progression in relapsed or refractory chronic
lymphocytic leukaemia (CLL).
The ASC trial compared Calquence with the physician's choice of
rituximab combined with idelalisib (IdR) or bendamustine (BR) in
patients with relapsed or refractory CLL.
At a median follow-up of 16.1 months, results from the trial
showed a statistically-significant and clinically-meaningful
improvement in progression-free survival (PFS) for patients treated
with Calquence vs. IdR or BR, reducing the risk of disease
progression or death by 69% (HR, 0.31; 95% CI, 0.20-0.49,
p<0.0001). The median time without disease progression for
patients treated with Calquence has not yet been reached vs. 16.5
months in the control arm. At 12 months, 88% of patients on
Calquence showed no disease progression compared to 68% for the
control arm. The safety and tolerability of Calquence was
consistent with its established profile.
José Baselga, Executive Vice President, Oncology R&D said:
"These data add to the growing body of evidence to support the
profile of Calquence as a selective BTK inhibitor that offers a
chemotherapy-free treatment option with a favourable safety profile
in chronic lymphocytic leukaemia, a life-threatening disease. These
data, along with our recent positive results from the Phase III
ELEVATE-TN trial in previously-untreated chronic lymphocytic
leukaemia, will serve as the foundation for regulatory submissions
later this year."
Paolo Ghia, MD, Professor, Medical Oncology, Università
Vita-Salute San Raffaele in Milan, and investigator of the ASC
trial, said: "This is the first randomised trial to directly
compare a BTK inhibitor as monotherapy with standard
chemoimmunotherapy or idelalisib and rituximab combinations. With a
significant improvement in progression-free survival and a
favourable safety profile, acalabrutinib may become an important
choice for the treatment of patients with relapsed or refractory
chronic lymphocytic leukaemia."
Kaplan-Meier plot for PFS as assessed by an independent review
committee in the intent-to-treat population(1)
Link to graph:
http://www.rns-pdf.londonstockexchange.com/rns/4350C_1-2019-6-17.pdf
Safety overview
Calquence IdR BR
(n=154) (n=118) (n=35)
Most common Any Grade Any Grade Any Grade >=3
(>=15%) >=3 >=3
AEs, n (%)
---------- ---------- ---------- ---------- -------- ---------
Headache 34 (22%) 1 (1%) 7 (6%) 0 0 0
---------- ---------- ---------- ---------- -------- ---------
Neutropenia 30 (19%) 24 (16%) 53 (45%) 47 (40%) 12 (34%) 11 (31%)
---------- ---------- ---------- ---------- -------- ---------
Diarrhoea 28 (18%) 2 (1%) 55 (47%) 28 (24%) 5 (14%) 0
---------- ---------- ---------- ---------- -------- ---------
Anaemia 23 (15%) 18 (12%) 11 (9%) 8 (7%) 4 (11%) 3 (9%)
---------- ---------- ---------- ---------- -------- ---------
Cough 23 (15%) 0 18 (15%) 1 (1%) 2 (6%) 0
---------- ---------- ---------- ---------- -------- ---------
Pyrexia 19 (12%) 1 (1%) 21 (18%) 8 (7%) 6 (17%) 1 (3%)
---------- ---------- ---------- ---------- -------- ---------
Fatigue 15 (10%) 2 (1%) 10 (8%) 0 8 (23%) 1(3%)
---------- ---------- ---------- ---------- -------- ---------
Nausea 11 (7%) 0 15 (13%) 1 (1%) 7 (20%) 0
---------- ---------- ---------- ---------- -------- ---------
IRR 0 0 9 (8%) 2 (2%) 8 (23%) 1 (3%)
---------- ---------- ---------- ---------- -------- ---------
Events of clinical interest for Calquence
Atrial fibrillation 8 (5%) 2 (1%) 4 (3%) 1 (1%) 1 (3%) 1 (3%)
---------- ---------- ---------- ---------- -------- ---------
Bleeding 40 (26%) 3 (2%) 9 (8%) 3 (3%) 2 (6%) 1(3%)
---------- ---------- ---------- ---------- -------- ---------
Hypertension 5 (3%) 3 (2%) 5 (4%) 1 (1%) 0 0
---------- ---------- ---------- ---------- -------- ---------
SPM* excluding
NMSC** 10 (6%) 5 (3%) 3 (3%) 0 1 (3%) 1 (3%)
---------- ---------- ---------- ---------- -------- ---------
*Secondary primary malignancy **Non-melanoma skin cancer.
AstraZeneca recently announced that the Phase III ELEVATE-TN
trial met its primary endpoint at interim analysis in patients with
previously-untreated CLL and that full results will be reported at
a forthcoming medical meeting. Calquence is currently approved for
the treatment of adults with relapsed or refractory mantle cell
lymphoma (MCL) in the US, Brazil, the United Arab Emirates, and
Qatar and is being developed for the treatment of CLL and other
blood cancers.
About ASC
ASC (ACE-CL-309) is a global, randomised, multicentre,
open-label Phase III trial evaluating the efficacy of Calquence in
previously-treated patients with CLL.(2) In the trial, 310 patients
were randomised (1:1) into two arms. Patients in the first arm
received Calquence monotherapy (100mg twice daily until disease
progression). Patients in the second arm received physician's
choice of either rituximab in combination with idelalisib or
rituximab in combination with bendamustine.(1,2)
The primary endpoint is PFS assessed by an independent review
committee (IRC), and key secondary endpoints include
physician-assessed PFS, IRC- and physician-assessed overall
response rate (ORR) and duration of response (DoR), as well as
overall survival (OS), patient reported outcomes (PROs) and time to
next treatment (TTNT).(1,2)
About Calquence
Calquence (acalabrutinib) was granted accelerated approval by
the US Food and Drug Administration (FDA) in October 2017 for the
treatment of adult patients with MCL who have received at least one
prior therapy. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in
confirmatory trials.
Calquence is an inhibitor of Bruton tyrosine kinase (BTK).
Calquence binds covalently to BTK, thereby inhibiting its
activity.(3) In B-cells, BTK signalling results in activation of
pathways necessary for B-cell proliferation, trafficking,
chemotaxis, and adhesion.
As part of an extensive clinical development programme,
AstraZeneca and Acerta Pharma are currently evaluating Calquence in
26 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, Waldenstrom macroglobulinaemia,
follicular lymphoma, and multiple myeloma and other haematologic
malignancies. Beyond the positive Phase III trials ASC and
ELEVATE-TN, other Phase III trials in CLL are ongoing, including
ELEVATE-RR (ACE-CL-006) evaluating acalabrutinib vs. ibrutinib in
patients with previously-treated high-risk CLL, and ACE-CL-311
evaluating acalabrutinib in combination with venetoclax and
with/without obinutuzumab in patients with previously-untreated CLL
without 17p deletion or TP53 mutation.
About chronic lymphocytic leukaemia
Chronic lymphocytic leukaemia (CLL) is the most common type of
leukaemia in adults, with an estimated 191,000 new cases globally
and 20,720 new cases in the US annually, and prevalence that is
expected to grow with improved treatment.(4-7) In CLL, too many
blood stem cells in the bone marrow become abnormal lymphocytes and
these abnormal cells have difficulty fighting infections.(4) As the
number of abnormal cells grows there is less room for healthy white
blood cells, red blood cells and platelets.(4) This could result in
anaemia, infection and bleeding.(4) B-cell receptor signalling
through BTK is one of the essential growth pathways for CLL.
About AstraZeneca in haematology
Leveraging its strength in oncology, AstraZeneca has established
haematology as one of four key oncology disease areas of focus. The
Company's haematology franchise includes two US FDA-approved
medicines and a robust global development programme for a broad
portfolio of potential blood cancer treatments. Acerta Pharma
serves as AstraZeneca's haematology research and development arm.
AstraZeneca partners with like-minded science-led companies to
advance the discovery and development of therapies to address unmet
need.
In October 2018, AstraZeneca and Innate Pharma announced a
global strategic collaboration that included Innate Pharma
licensing the US commercial rights of Lumoxiti (moxetumomab
pasudotox-tdfk), and with support from AstraZeneca, will continue
EU development and commercialisation, pending regulatory submission
and approval.
About 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 at
least six new medicines to be launched between 2014 and 2020, and a
broad pipeline of small molecules and biologics in development, we
are committed to advance oncology as a key growth driver for
AstraZeneca focused on lung, ovarian, breast and blood cancers. In
addition to our core capabilities, we actively pursue innovative
partnerships and investments that accelerate the delivery of our
strategy as illustrated by our investment in Acerta Pharma in
haematology.
By harnessing the power of four scientific platforms -
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response
and Antibody Drug Conjugates - and by championing the development
of personalised 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 commercialisation 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.com and follow us on Twitter @AstraZeneca.
Media Relations
Gonzalo Viña +44 203 749 5916
Rob Skelding Oncology +44 203 749 5821
Rebecca Einhorn Oncology +1 301 518 4122
Matt Kent BioPharma +44 203 749 5906
Jennifer Hursit Other +44 203 749 5762
Christina Malmberg Hägerstrand Sweden +46 8 552 53 106
Michele Meixell US +1 302 885 2677
Investor Relations
Thomas Kudsk Larsen +44 203 749 5712
Henry Wheeler Oncology +44 203 749 5797
Christer Gruvris BioPharma (cardiovascular; metabolism) +44 203 749 5711
Nick Stone BioPharma (respiratory; renal) +44 203 749 5716
Josie Afolabi Other medicines +44 203 749 5631
Craig Marks Finance, fixed income +44 7881 615 764
Jennifer Kretzmann Corporate access, retail investors +44 203 749 5824
US toll-free +1 866 381 72 77
Adrian Kemp
Company Secretary
AstraZeneca PLC
References
1 Ghia P, Pluta A, Wach M, et al. ASCEND Phase 3 study of
acalabrutinib vs. investigator's choice of rituxumab plus
idelalisib (idR) or bendamustine (BR) in patients with
relapsed/refractory chronic lymphocytic leukaemia (CLL). Abstract
LB2606 at: European Hematology Association 2019 Annual Meeting.
Available online. Accessed June 2019.
2 ClinicalTrials.gov. A Study of Acalabrutinib vs Investigator's
Choice of Idelalisib Plus Rituximab or Bendamustine Plus Rituximab
in R/R CLL. NCT02970318. Available online. Accessed June 2019.
3 CALQUENCE(R) (acalabrutinib) Prescribing Information.
AstraZeneca Pharmaceuticals LP, Wilmington, DE.
4 National Cancer Institute. Chronic Lymphocytic Leukaemia
Treatment (PDQ(R))-Patient Version. Available online. Accessed June
2019.5Global Burden of Disease Cancer Collaboration. JAMA Oncol.
2017;3(4):524-528.
5 Global Burden of Disease Cancer Collaboration. JAMA Oncol.
2017;3(4):524-52.
6 National Institute of Health SEER Program. Cancer Stat Facts:
Leukemia-Chronic Lymphocytic Leukemia (CLL). Available online.
Accessed June 2019.
7 Jain N, et al. Prevalence and Economic Burden of Chronic
Lymphocytic Leukemia (CLL) in the Era of Oral Targeted Therapies.
Blood. 2015;126:871.
This information is provided by RNS, the news service of the
London Stock Exchange. RNS is approved by the Financial Conduct
Authority to act as a Primary Information Provider in the United
Kingdom. Terms and conditions relating to the use and distribution
of this information may apply. For further information, please
contact rns@lseg.com or visit www.rns.com.
END
MSCEDLBFKQFLBBQ
(END) Dow Jones Newswires
June 17, 2019 02:00 ET (06:00 GMT)
Astrazeneca (LSE:AZN)
Historical Stock Chart
From Mar 2024 to Apr 2024
Astrazeneca (LSE:AZN)
Historical Stock Chart
From Apr 2023 to Apr 2024
