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 April 2025
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.
Fixed-duration Calquence recommended in EU for CLL
29 April 2025
Fixed-duration Calquence-based
regimens recommended for approval
in the EU by CHMP for 1st-line chronic lymphocytic
leukaemia
Recommendation based on AMPLIFY Phase III trial which showed
Calquence combinations demonstrated statistically significant and
clinically meaningful improvement in progression-free survival vs.
chemoimmunotherapy
A fixed-duration regimen of AstraZeneca's Calquence (acalabrutinib) in combination with
venetoclax, with or without obinutuzumab, has been recommended for
approval in the European Union (EU) for the treatment of adult
patients with previously untreated chronic lymphocytic leukaemia
(CLL).
The Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency (EMA) based its positive opinion on
results from the AMPLIFY Phase III
trial, which were presented at
the American Society of Haematology (ASH) 2024 Annual Meeting and
published in The
New England Journal of Medicine.1
Results showed Calquence plus venetoclax reduced the risk of disease
progression or death by 35% compared to standard-of-care
chemoimmunotherapy (investigator's choice of
fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab;
hazard ratio [HR] 0.65; 95% confidence interval [CI] 0.49-0.87;
p=0.0038). Calquence plus
venetoclax with obinutuzumab demonstrated a 58% reduction in the
risk of disease progression or death compared to standard-of-care
chemoimmunotherapy (HR 0.42; 95% CI 0.30-0.59;
p<0.0001).2
At three years, 77% of patients treated
with Calquence plus venetoclax and 83% of patients treated
with Calquence plus venetoclax and obinutuzumab were
progression free, versus 67% of patients treated with
chemoimmunotherapy.1 Median
progression-free survival (PFS) was not reached for either
experimental arm versus 47.6 months for
chemoimmunotherapy.1
Wojciech Jurczak, MD, Maria Sklodowska-Curie National Institute of
Oncology, Kraków, Poland and investigator for the trial, said:
"Chronic lymphocytic leukaemia is an incurable cancer which means
patients live with the disease and stay on treatment for many
years, which can have long-term effects. The
fixed-duration Calquence regimens will allow patients to take breaks
from their treatment, reducing the risk of long-term adverse events
and drug resistance."
Susan Galbraith, Executive Vice President, Oncology Haematology
R&D, AstraZeneca, said: "With this
recommendation, Calquence plus venetoclax can potentially be the only
all-oral second-generation BTK inhibitor option approved in Europe
for patients with previously untreated chronic lymphocytic
leukaemia. Calquence has demonstrated efficacy and safety in
fixed-duration and treat-to-progression regimens providing patients
and their doctors more treatment flexibility."
CLL is the most common type of leukaemia in adults, with an
estimated 27,000 patients diagnosed in the UK, France, Germany,
Spain and Italy in 2024.3
The safety and tolerability of Calquence was consistent with its known safety
profile, and no new safety signals were
identified.
Regulatory applications for Calquence plus venetoclax, with or without
obinutuzumab, in this setting are currently under review in several
countries based on the AMPLIFY results.
Notes
Chronic lymphocytic leukaemia (CLL)
CLL is the most prevalent type of leukaemia in adults, with over
117,000 new cases globally in 2021.4 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.5 In
CLL, there is an accumulation of abnormal lymphocytes within the
blood, bone marrow and lymph nodes. 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.6 This
could result in infection, anaemia and bleeding. B-cell receptor
signalling through BTK is one of the essential growth pathways for
CLL.
AMPLIFY
AMPLIFY is a randomised, global, multi-centre, open-label Phase III
trial evaluating the efficacy and safety
of Calquence in
combination with venetoclax, with or without obinutuzumab, compared
to investigator's choice of chemoimmunotherapy
(fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab)
in adult patients with previously untreated CLL without del(17p)
or TP53 mutation.7 Patients
were randomised 1:1:1 to receive either Calquence plus venetoclax, Calquence plus venetoclax with obinutuzumab for a
fixed duration or standard-of-care
chemoimmunotherapy.7 Both
the Calquence containing arms were administered for a
fixed duration of 14 cycles (each 28 days), and the
standard-of-care chemoimmunotherapy was for 6
cycles.7
The primary endpoint is PFS in the Calquence and venetoclax arm as assessed by an
Independent Review Committee and PFS in
the Calquence plus
venetoclax with obinutuzumab is a key secondary
endpoint.7 Other
key secondary endpoints include OS and undetectable measurable
residual disease.7 The
trial includes 27 countries across North and South America, Europe,
Asia and Oceania.7
The AMPLIFY trial enrolled patients from 2019 to 2021, continuing
through the COVID-19 pandemic.7 Patients
with blood cancer remain at a disproportionately high risk of
severe outcomes from COVID-19, including hospitalisation and death
compared to the general population.8
Calquence
Calquence (acalabrutinib)
is a second-generation, selective inhibitor of Bruton's tyrosine
kinase (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 chronic lymphocytic
leukaemia (CLL) and small lymphocytic lymphoma (SLL) in the US,
Japan and China, approved for CLL in the EU and many other
countries worldwide. Calquence is also approved for the treatment
of adult patients with previously untreated MCL in the US and other
countries. It is also approved for the treatment of adult patients
with MCL who have received at least one prior therapy in China and
several other countries. Calquence is not currently approved for
the treatment of MCL in Japan.
As part of an extensive clinical development programme, Calquence
is currently being evaluated as a single treatment and in
combination with standard-of-care chemoimmunotherapy for patients
with multiple B-cell blood cancers, including CLL, MCL and diffuse
large B-cell lymphoma.
AstraZeneca in haematology
AstraZeneca is pushing the boundaries of science to redefine care
in haematology. Our goal is to help transform the lives of patients
living with malignant, rare and other related haematologic diseases
through innovative medicines and approaches that are shaped by
insights from patients, caregivers and
physicians.
In addition to our marketed products, we are spearheading the
development of novel therapies designed to target underlying
drivers of disease across multiple scientific platforms. Our
acquisitions of Alexion, with expertise in rare, non-malignant
blood disorders, and Gracell Biotechnologies Inc., pioneers of
autologous cell therapies, expand our haematology pipeline and
enable us to reach more patients with high unmet needs through the
end-to-end discovery, development and delivery of novel
therapies.
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's innovative
medicines are sold in more than 125 countries and used by millions
of patients worldwide. Please visit astrazeneca.com and
follow the Company on Social Media @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. Brown J, et al. Fixed-Duration
Acalabrutinib Combinations in Untreated Chronic Lymphocytic
Leukemia. NEJM. 2025;392:748-762.
2.
Brown, J et al. Fixed-Duration Acalabrutinib plus Venetoclax with
or without Obinutuzumab versus Chemoimmunotherapy for First-Line
Treatment of Chronic Lymphocytic Leukemia: Interim Analysis of the
Multicenter, Open-label, Randomized, Phase 3 AMPLIFY Trial.
Presented at ASH 2024. Abstract 1009. 2024.
3. AstraZeneca 2024. Full Year and Q4
2024 Financial Results Epidemiology Spreadsheet. Available
at: https://www.astrazeneca.com/investor-relations.html.
Accessed April 2025.
4.
Global Burden of Disease Collaborative Network's "Global Burden of
Disease Study 2021 (GBD 2021)" published by the Institute for
Health Metrics and Evaluation (IHME) in Seattle, United States, in
2024. Accessed April 2025.
5. American Cancer Society. Signs and
Symptoms of Chronic Lymphocytic Leukemia. Available
at: https://www.cancer.org/cancer/types/chronic-lymphocytic-leukemia/detection-diagnosis-staging/signs-symptoms.html.
Accessed April 2025.
6. National Cancer Institute. Chronic
lymphocytic leukemia treatment (PDQ®)-Patient
version. Available at: https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq.
Accessed April 2025.
7. ClinicalTrials.gov. Study of
Acalabrutinib (ACP-196) in Combination With Venetoclax (ABT-199),
With and Without Obinutuzumab (GA101) Versus Chemoimmunotherapy for
Previously Untreated CLL (AMPLIFY). Available
at: https://clinicaltrials.gov/study/NCT03836261.
Accessed April 2025.
8.
Dube S, et al. Continued Increased Risk of COVID-19 Hospitalisation
and Death in Immunocompromised Individuals Despite Receipt of
≥4 Vaccine Doses: Updated 2023 Results from INFORM, a
Retrospective Health Database Study in England. Poster P0409 at
ECCMID 2024.
9. Wu J, et al. 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.
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AstraZeneca
PLC
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Date:
29 April 2025
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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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