a6391e
FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of November 2020
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
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United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Calquence
approved in the EU for CLL
9 November 2020 07:00 GMT
Calquence approved in the EU for
the
treatment of chronic lymphocytic leukaemia
Calquence demonstrated superior progression-free survival and
favourable tolerability in both previously untreated and relapsed
or refractory patients
AstraZeneca's Calquence (acalabrutinib), a next-generation selective
Bruton's tyrosine kinase (BTK) inhibitor, has been approved in the
European Union (EU) for the
treatment of adult patients with chronic lymphocytic leukaemia
(CLL), the most common type of leukaemia in
adults.
The approval by the European Commission was based on
positive results from two Phase III clinical trials, ELEVATE-TN in
patients with previously untreated CLL and ASCEND in patients with
relapsed or refractory CLL.1,2 This
follows a recommendation for
approval by the Committee
for Medicinal Products for Human Use of the European Medicines
Agency in July 2020.
Paolo Ghia, MD, Director, Strategic Research Program on CLL,
Università Vita-Salute San Raffaele in Milan, and investigator
of the ASCEND Phase III trial, said: "One of our biggest hurdles in
treating chronic lymphocytic leukaemia is finding tolerable
treatment options that manage the disease long term, which
typically impacts older patients with comorbidities. Today's news
marks great progress for patients in Europe, as the Phase III
clinical trials for Calquence showed a significant improvement in
comparison with current standard treatments."
Dave Fredrickson, Executive Vice President, Oncology Business Unit,
said: "This approval represents a key development for patients in
Europe who until now have had limited chemotherapy-free treatment
options. As our first European approval in blood
cancers, Calquence provides a new tolerable treatment option
with uncompromised efficacy and the potential to positively impact
the quality of life for thousands of patients living with chronic
lymphocytic leukaemia."
In the ELEVATE-TN Phase III trial, Calquence combined with obinutuzumab and as
monotherapy reduced the risk of disease progression or death by 90%
and 80%, respectively, compared with standard chemo-immunotherapy
treatment chlorambucil plus obinutuzumab, in patients with
previously untreated CLL.1 In
the ASCEND Phase III trial, 88% of patients with relapsed or
refractory CLL taking Calquence remained alive and free from disease
progression after 12 months compared with 68% of patients on
rituximab combined with idelalisib or
bendamustine.2 Data
from the interim results of the trials were published
in The
Lancet and Journal
of Clinical Oncology,
respectively.
Calquence is approved for
the treatment of CLL and small lymphocytic lymphoma in the US and
is approved for CLL in several other countries
worldwide. Calquence is also approved for the treatment of adult
patients with mantle cell lymphoma (MCL) who have received at least
one prior therapy in the US and several other
countries. Calquence is not currently approved for the treatment
of MCL in Europe.
As part of a broad development programme, Calquence is being assessed in more than 20
AstraZeneca-sponsored clinical trials for the treatment of patients
with B-cell malignancies including CLL, MCL, diffuse large B-cell
lymphoma (DLBCL), Waldenström's macroglobulinaemia (WM),
follicular lymphoma (FL), and other haematologic
malignancies.
Chronic lymphocytic leukaemia
Chronic lymphocytic leukaemia (CLL) is the most common type of
leukaemia in adults, with an estimated 105,000 new cases globally
in 2016, and the number of people living with CLL is expected to
grow with improved treatment as patients live longer with the
disease.3,4,5,6 In
CLL, too many blood stem cells in the bone marrow become abnormal
lymphocytes and these abnormal cells have difficulty fighting
infections. As the number of abnormal cells grows there is less
room for healthy white blood cells, red blood cells, and platelets.
This could result in anaemia, infection, and
bleeding.4 B-cell
receptor signalling through BTK is one of the essential growth
pathways for CLL.
ELEVATE-TN
ELEVATE-TN (ACE-CL-007) was a randomised, multicentre, open-label
Phase III trial evaluating the safety and efficacy
of Calquence in combination with obinutuzumab, a CD20
monoclonal antibody, or Calquence alone versus chlorambucil, a chemotherapy,
in combination with obinutuzumab in previously untreated patients
with CLL. Patients 65 years of age or older, or between 18 and 65
years of age with a total Cumulative Illness Rating Scale >6 or
creatinine clearance of 30 to 69mL/min, were enrolled. In the
trial, 535 patients were randomised (1:1:1) into three arms.
Patients in the first arm received chlorambucil in combination with
obinutuzumab. Patients in the second arm
received Calquence (100mg approximately every 12 hours until
disease progression or unacceptable toxicity) in combination with
obinutuzumab. Patients in the third arm
received Calquence monotherapy (100mg approximately every 12
hours until disease progression or unacceptable
toxicity).1
The primary endpoint was progression-free survival (PFS) in
the Calquence and obinutuzumab arm compared to the
chlorambucil and obinutuzumab arm, assessed by an independent
review committee (IRC), and a key secondary endpoint was
IRC-assessed PFS in the Calquence monotherapy arm compared to the chlorambucil
and obinutuzumab arm. Other secondary endpoints included objective
response rate, time to next treatment and overall survival
(OS).1
ASCEND
ASCEND (ACE-CL-309) was a global, randomised, multicentre,
open-label Phase III trial evaluating the efficacy
of Calquence in patients with relapsed or refractory CLL.
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 or unacceptable toxicity). Patients in the second arm
received investigator's choice of either rituximab, a CD20
monoclonal antibody, in combination with idelalisib, a PI3K
inhibitor, or rituximab in combination with bendamustine, a
chemotherapy.2
The primary endpoint was PFS assessed by an IRC, and key secondary
endpoints included physician-assessed PFS, IRC- and
physician-assessed overall response rate and duration of response,
as well as OS, patient-reported outcomes and time to next
treatment.2
Calquence
Calquence (acalabrutinib)
is a next-generation, selective inhibitor of
BTK. Calquence binds covalently to BTK, thereby inhibiting
its activity.7,8 In
B-cells, BTK signalling results in activation of pathways necessary
for B-cell proliferation, trafficking, chemotaxis, and
adhesion.7
As part of an extensive clinical development programme, 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, DLBCL, WM, FL,
and other haematologic malignancies.
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 medicines approved by
the US Food and Drug Administration 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.
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
haematology.
By harnessing the power of six scientific platforms -
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage
Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies
- 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.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) 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
& Immunology. Based in Cambridge, UK, AstraZeneca operates in
over 100 countries and its innovative medicines are used by
millions of patients worldwide. Please
visit astrazeneca.com and
follow the Company on Twitter @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. Sharman JP, et al. ELEVATE TN: Phase 3 Study of Acalabrutinib
Combined with Obinutuzumab (O) or Alone Vs O Plus Chlorambucil
(Clb) in Patients (Pts) with Treatment-Naive Chronic Lymphocytic
Leukemia (CLL). Blood. 2019; 134 (Supplement_1): 31.
doi:10.1182/blood-2019-128404.
2. Ghia P, et al. ASCEND: Phase III, Randomized Trial of
Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus
Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia
[published online ahead of print, 2020 May
27]. J
Clin Oncol. 2020; JCO1903355.
doi:10.1200/JCO.19.03355.
3. American Cancer Society. What is Chronic Lymphocytic Leukemia?
Available at https://www.cancer.org/cancer/chronic-lymphocytic-leukemia/about/what-is-cll.html.
Accessed August 2020.
4. National Cancer Institute. Chronic Lymphocytic Leukemia
Treatment (PDQ®)-Patient Version. Available at
https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq.
Accessed August 2020.
5. Global Burden of Disease Cancer Collaboration. Global, Regional,
and National Cancer Incidence, Mortality, Years of Life Lost, Years
Lived With Disability, and Disability-Adjusted Life-Years for 29
Cancer Groups, 1990 to 2016. JAMA Oncol. 2018;4(11):1553-1568.
6. Jain N, et al. Prevalence and Economic Burden of Chronic
Lymphocytic Leukemia (CLL) in the Era of Oral Targeted
Therapies. Blood. 2015;126:871.
7. Calquence® (acalabrutinib)
[prescribing information]. Wilmington, DE; AstraZeneca
Pharmaceuticals LP; 2019.
8. Wu J, Zhang M & Liu D. Acalabrutinib (ACP-196): a selective
second-generation BTK inhibitor. J Hematol
Oncol.
2016;9(21).
Adrian Kemp
Company Secretary
AstraZeneca PLC
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
Date:
09 November 2020
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|