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 December 2022
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
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United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Calquence Japan approval for treatment-naïve CLL
28 December 2022 07:05 GMT
Calquence approved
in Japan for adults with
treatment-naïve chronic lymphocytic leukaemia
Calquence significantly increased the time patients lived without
disease progression or death vs. chemoimmunotherapy
AstraZeneca's Calquence (acalabrutinib), a selective Bruton's
tyrosine kinase (BTK) inhibitor, has been approved in Japan for the
treatment of adult patients with treatment-naïve chronic
lymphocytic leukaemia (CLL) (including small lymphocytic lymphoma
[SLL]). Calquence was
previously approved in
Japan for the treatment of adults with relapsed or refractory
CLL.
The approval by the Japanese Ministry of Health, Labour
and Welfare (MHLW) was based on positive results
from two clinical trials, including the ELEVATE-TN Phase III
trial in adults with treatment-naïve
CLL. This trial showed that Calquence combined
with obinutuzumab or as monotherapy demonstrated a significantly
improved progression-free survival (PFS) when compared with the
chemotherapy-based combination of chlorambucil and
obinutuzumab.1,2 Data
from the interim analysis of ELEVATE-TN was published
in The
Lancet in
2020.2 Additionally,
a Phase I trial in treatment-naïve Japanese patients with CLL
was also submitted to MHLW supporting the approval, with the trial
showing an overall response rate of 88.9% (95% CI: 63.2, 98.8%)
for Calquence alone and 100% (95% CI: 66.4, 100%)
for Calquence combined with
obinutuzumab.
CLL is the most prevalent type of adult leukaemia across the
globe but is considered a rare disease in Japan and East Asia,
with fewer than one person newly diagnosed per 100,000 persons per
year across Japan.3-5
Koji Izutsu, MD, PhD, Department Head, Department of Hematology,
National Cancer Center Hospital, Tokyo, Japan, said: "Results from
ELEVATE-TN and our local Japanese trial confirm
that Calquence provides a significant improvement in
progression-free survival compared with chemotherapy-based
combination of chlorambucil and obinutuzumab for patients with
treatment-naïve chronic lymphocytic leukaemia. Today's
approval marks great progress for physicians and patients in Japan,
as they can now be treated with Calquence earlier in their treatment
journey."
Dave Fredrickson, Executive Vice President, Oncology Business Unit,
AstraZeneca, said: "The approval of Calquence in Japan for those with treatment-naïve
chronic lymphocytic leukaemia now offers more patients a
next-generation Bruton's tyrosine kinase inhibitor that has proven
longer-term efficacy and tolerability compared to standards of
care. With this approval, people living with chronic lymphocytic
leukaemia in Japan can now potentially benefit from our medicine in
an earlier setting."
Updated results of the ELEVATE-TN Phase III trial after a median
follow-up of approximately five years were presented earlier
this year. These results showed that Calquence maintained a statistically significant PFS
benefit versus chlorambucil plus obinutuzumab, and a safety and
tolerability profile consistent with the known profile
for Calquence. At a median follow-up of 58.2
months, Calquence plus obinutuzumab reduced the risk of
disease progression or death by 89% (based on a hazard ratio [HR]
of 0.11, 95% confidence interval [CI] 0.07-0.16) and as a
monotherapy by 79% (based on a HR of 0.21, 95% CI 0.15-0.30),
compared with chlorambucil plus obinutuzumab.1
Calquence is approved for
the treatment of CLL and SLL in the US and
is approved for
the treatment of CLL in the EU and in several other countries
worldwide in the treatment-naïve and relapsed or refractory
settings. Calquence is also approved in the US and several other
countries for the treatment of adult patients with mantle cell
lymphoma (MCL) who have received at least one prior
therapy. Calquence is not currently approved for the treatment
of MCL in Japan or the EU.
Notes
CLL
CLL is the most prevalent type of leukaemia in adults, with over
100,000 new cases globally in 2019, but is considered a rare
disease in Japan and East Asia, with fewer than one person newly
diagnosed per 100,000 persons per year across
Japan.3-5 Although
some people with CLL may not experience any symptoms at diagnosis,
others may experience symptoms, such as weakness, fatigue, weight
loss, chills, fever, night sweats, swollen lymph nodes and
abdominal pain.6
In CLL, there is an accumulation of abnormal lymphocytes within the
bone marrow. As the number of abnormal cells increases, there is
less room within the marrow for the production of normal white
blood cells, red blood cells and platelets.7 This
could result in anaemia, infection and bleeding. B-cell
receptor signalling through BTK is one of the essential growth
pathways for CLL.
ELEVATE-TN
ELEVATE-TN (ACE-CL-007) is a randomised, multicentre, open-label
Phase III trial evaluating the safety and efficacy
of Calquence alone or in combination with obinutuzumab
versus chlorambucil in combination with obinutuzumab in previously
untreated patients with CLL. 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 twice daily until disease
progression) in combination with obinutuzumab. Patients in the
third arm received Calquence monotherapy (100mg twice daily until disease
progression).8
The primary endpoint was 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
overall response rate, time to next treatment, overall survival and
investigator assessed PFS. After interim analysis, assessments were
by investigator only.8
Initial results from the ELEVATE-TN Phase III trial were presented
in December 2019 at the American Society of Hematology Annual
Meeting and Exhibition. The trial met its primary endpoint
(IRC-assessed PFS with Calquence plus obinutuzumab versus chlorambucil plus
obinutuzumab) at the data cut-off for the interim analysis after a
median follow-up of 28.3 months. The findings, along with
previously reported data from the ASCEND Phase III trial in
relapsed or refractory CLL, supported the approvals
of Calquence by the US FDA and the Australian Therapeutic
Goods Administration for the treatment of adult patients with CLL
or SLL and by the European Medicines Agency (EMA) and Health Canada
for CLL.
Calquence
Calquence (acalabrutinib)
is a next-generation, selective inhibitor of
BTK. Calquence binds covalently to BTK, thereby inhibiting
its activity.9 In
B cells, BTK signalling results in activation of pathways necessary
for B-cell proliferation, trafficking, chemotaxis and
adhesion.
Calquence is approved for
the treatment of CLL and SLL in the US, approved for CLL in the EU
and many other countries worldwide and approved in Japan for
relapsed or refractory CLL and SLL.
In the US and several other countries, Calquence is
also approved for the treatment of adult patients with MCL who have
received at least one prior therapy. The US MCL 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
not currently approved for the treatment of MCL in Europe or
Japan.
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 evaluated for the treatment of
multiple B-cell blood cancers, including CLL, MCL, diffuse large
B-cell lymphoma, Waldenström's macroglobulinaemia, marginal
zone lymphoma and other haematologic
malignancies.
AstraZeneca in haematology
AstraZeneca is pushing the boundaries of science to redefine care
in haematology. We have expanded our commitment to patients with
haematologic conditions, not only in oncology but also in rare
diseases with the acquisition of Alexion, allowing us to reach more
patients with high unmet needs. By applying our deep understanding
of blood cancers, leveraging our strength in solid tumour oncology
and delivering on Alexion's pioneering legacy in complement science
to provide innovative medicines for rare diseases, we are pursuing
the end-to-end development of novel therapies designed to target
underlying drivers of disease.
By targeting haematologic conditions with high unmet medical needs,
we aim to deliver innovative medicines and approaches to improve
patient outcomes. Our goal is to help transform the lives of
patients living with malignant, rare and other related haematologic
diseases, shaped by insights from patients, caregivers and
physicians to have the most meaningful impact.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition
to provide cures for cancer in every form, following the science to
understand cancer and all its complexities to discover, develop and
deliver life-changing medicines to patients.
The Company's focus is on some of the most challenging cancers. It
is through persistent innovation that AstraZeneca has built one of
the most diverse portfolios and pipelines in the industry, with the
potential to catalyse changes in the practice of medicine and
transform the patient experience.
AstraZeneca has the vision to redefine cancer care 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 in
Oncology, Rare Diseases and BioPharmaceuticals, including
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, Egyed M, Jurczak W, et
al. Acalabrutinib ±
Obinutuzumab vs Obinutuzumab + Chlorambucil in Treatment-Naïve
Chronic Lymphocytic Leukemia: 5-Year Follow-up of ELEVATE-TN
[abstract and poster]. Presented at: American Society for Clinical
Oncology (ASCO) Annual Meeting; June 3-7, 2022. Abstract ID:
7539.
2. Sharman JP, Egyed M, Jurczak
W, et
al. Acalabrutinib with or
without obinutuzumab versus chlorambucil and obinutuzumab for
treatment-naive chronic lymphocytic leukaemia (ELEVATE-TN):
a randomized, controlled, phase 3
trial. Lancet. 2020;395:1278-1291.
doi:10.1182/blood-2019-128404.
3. Yao Y, Lin X, Li
F, et
al. The global burden and
attributable risk factors of chronic lymphocytic leukemia in 204
countries and territories from 1990 to 2019: analysis based on the
global burden of disease study 2019. Biomed Eng
Online. 2022;1: 4. doi:
10.1186/s12938-021-00973-6.
4. Mahlich J, Okamoto S, Tsubota A. Cost of
Illness of Japanese Patients with Chronic Lymphocytic Leukemia
(CLL), and Budget Impact of the Market Introduction of
Ibrutinib. Pharmacoecon
Open. 2017;1(3):195-202.
doi:10.1007/s41669-017-0024-5.
5. National Cancer
Institute Cancer Information Service. Chronic Lymphocytic
Leukemia/Small Lymphocytic Lymphoma. Available
at: https://ganjoho.jp/public/cancer/CLL/index.html.
Accessed November 2022.
6. American Cancer Society.
Signs and Symptoms of Chronic Lymphocytic Leukemia.
Accessed online.
Accessed November 2022.
7. National Cancer
Institute. Chronic lymphocytic leukemia treatment
(PDQ®)-Patient version. Accessed online.
Accessed November 2022.
8.
ClinicalTrials.gov. ELEVATE CLL TN: Study of Obinutuzumab +
Chlorambucil, Acalabrutinib (ACP-196) + Obinutuzumab, and
Acalabrutinib in Subjects With Previously Untreated CLL. NCT
identifier: NCT02475681.
https://clinicaltrials.gov/ct2/show/NCT02475681. Accessed November
2022.
9. 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:
28 December 2022
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By: /s/
Adrian Kemp
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Name:
Adrian Kemp
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Title:
Company Secretary
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