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 January 2025
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Calquence combination approved in US for 1L MCL
17 January 2025
Calquence plus
chemoimmunotherapy approved
in the US for
patients with previously untreated mantle cell
lymphoma
Based on ECHO Phase III trial results which showed more than 16
months of progression-free survival improvement vs.
chemoimmunotherapy alone
First and only BTK inhibitor approved for the 1st-line treatment of
MCL in the US
AstraZeneca's Calquence (acalabrutinib) in combination with
bendamustine and rituximab has been approved in the US for the
treatment of adult patients with previously untreated mantle cell
lymphoma (MCL) who are ineligible for autologous hematopoietic stem
cell transplantation.
The approval was granted by the Food and Drug Administration (FDA)
after securing Priority
Review. It was based on results
from the ECHO Phase III trial which were presented at the European
Hematology Association 2024 Congress.
MCL is a rare and typically aggressive form of non-Hodgkin lymphoma
(NHL), often diagnosed at an advanced stage.[1],[2] It
is estimated that there are more than 21,000 patients diagnosed
with MCL in the US, UK, France, Germany, Spain, Italy, Japan and
China.[3]
Michael Wang, MD, Puddin Clarke Endowed Professor, Director of
Mantle Cell Lymphoma Program of Excellence and principal
investigator in the trial, said: "Managing this aggressive cancer
requires maximising efficacy while maintaining tolerability,
especially for elderly patients. Results from the pivotal ECHO
trial highlight the promise of the acalabrutinib combination in
defining a new standard of care, with today's approval underscoring
the transformative potential of this regimen as a first-line
treatment for older patients with mantle cell
lymphoma."
Dave Fredrickson, Executive Vice-President, Oncology Haematology
Business Unit, AstraZeneca, said: "With today's
approval, Calquence provides a critical new treatment option to
mantle cell lymphoma patients in the US,
with Calquence proven to deliver nearly one and a half
years of additional time without disease progression. This approval
brings a new and effective treatment option to those living with
this disease and further reinforces our belief
in Calquence as a backbone therapy across multiple blood
cancers."
Meghan Gutierrez, Chief Executive Officer, Lymphoma Research
Foundation, said: "New treatment options have long been needed in
the first-line treatment of mantle cell lymphoma in the US.
Patients with this rare and often aggressive cancer can experience
severe symptoms by the time they are diagnosed - having an
effective therapy that can significantly improve outcomes for
patients early in the treatment process is a much-needed
advancement."
Results from the ECHO trial showed Calquence plus
bendamustine and rituximab reduced the risk of disease progression
or death by 27% compared to standard-of-care chemoimmunotherapy
(hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.57-0.94;
p=0.016). Median PFS was 66.4 months for patients treated with
the Calquence combination
versus 49.6 months with chemoimmunotherapy
alone.
This approval additionally converts Calquence's accelerated approval to a full approval for
adult patients with MCL treated with at least one prior therapy, as
granted by the FDA in October 2017.
The ECHO trial enrolled patients throughout the COVID-19 pandemic.
After censoring for COVID-19 deaths, PFS was further improved in
both arms, with the Calquence combination reducing the risk of disease
progression or death by 36% (HR 0.64; 95% CI 0.48-0.84). Although
OS data were not mature at the time of the analysis, when censored
for COVID-19, a favourable trend was seen for OS (HR 0.75; 95% CI
0.53-1.04), despite 69% of patients in the chemoimmunotherapy arm
receiving treatment with a BTK inhibitor on relapse or disease
progression.
The safety and tolerability of Calquence was consistent with its known safety
profile, and no new safety signals were
identified.
The US regulatory submission was reviewed under Project Orbis,
which provides a framework for concurrent submission and review of
oncology medicines among participating international partners. As
part of Project Orbis, Calquence plus chemoimmunotherapy is also under review
by regulatory authorities in Australia, Canada, and Switzerland for
the same indication. Regulatory applications are also under review
in the EU, Japan, and other countries based on the ECHO
results.
Notes
Mantle cell lymphoma (MCL)
While MCL patients initially respond to treatment, patients do tend
to relapse.[4] MCL
comprises about 3-6% of non-Hodgkin lymphomas, with an annual
incidence of 0.5 per 100,000 population in Western countries; in
the US, it is estimated that approximately 4,000 new patients are
diagnosed with MCL each year.4,[5]
ECHO
ECHO is a randomised, double-blind, placebo-controlled,
multi-centre Phase III trial evaluating the efficacy and safety
of Calquence plus bendamustine and rituximab compared to
SoC chemoimmunotherapy (bendamustine and rituximab) in adult
patients at or over 65 years of age (n=635) with previously
untreated MCL.[6] Patients
were randomised 1:1 to receive either Calquence or placebo administered orally twice per
day, continuously, until disease progression or unacceptable
toxicity. Additionally, all patients received six 28-day cycles of
bendamustine on days 1 and 2 and rituximab on day 1 of each cycle,
followed by rituximab maintenance for two years if patients
achieved a response after induction therapy.6
The primary endpoint is PFS assessed by an Independent Review
Committee; other efficacy endpoints include OS, overall response
rate (ORR), duration of response (DoR) and time to response
(TTR).6 The
trial was conducted in 27 countries across North and South America,
Europe, Asia and Oceania.6
The ECHO trial enrolled patients from May 2017 to March 2023,
continuing through the COVID-19 pandemic. Prespecified PFS and OS
analyses censoring for COVID-19 deaths were conducted to assess the
impact of COVID-19 on the study outcome in alignment with the FDA.
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.6,[7]
Calquence
Calquence (acalabrutinib)
is a second-generation, selective inhibitor of Bruton's tyrosine
kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting
its activity.[8] In
B-cells, BTK signalling results in activation of pathways necessary
for B-cell proliferation, trafficking, chemotaxis and
adhesion.
Calquence has been used to
treat more than 85,000 patients worldwide[9] and
is approved for the treatment of chronic lymphocytic leukaemia
(CLL) and small lymphocytic lymphoma (SLL) in the US and Japan,
approved for CLL in the EU and many other countries worldwide and
approved in China for relapsed or refractory CLL and
SLL. Calquence is also approved for the treatment of adult
patients with previously untreated MCL in the US, and in China 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.
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. Lymphoma
Research Foundation. Mantle Cell Lymphoma. Available at:
https://lymphoma.org/aboutlymphoma/nhl/mcl/. Accessed January
2025.
2.
National Organization for Rare Disorders. Mantle Cell Lymphoma.
Available at:
https://rarediseases.org/rare-diseases/mantle-cell-lymphoma/.
Accessed January 2025.
3.
AstraZeneca 2024. Q3 2024 Financial Results. Available
at: https://www.astrazeneca.com/investor-relations.html.
Accessed January 2025.
4. Cheah
C, Seymour J, Wang ML. Mantle cell
lymphoma. J Clin
Oncol.
2016;34(11):1256-1269. doi:
10.1200/JCO.2015.63.5904.
5. MD
Anderson Cancer Center. What to know about mantle cell lymphoma.
Available at:
https://www.mdanderson.org/cancerwise/what-to-know-about-mantle-cell-lymphoma-symptoms-diagnosis-and-treatment.h00-159385101.html.
Accessed January 2025.
6. ClinicalTrials.gov.
A Study of BR Alone Versus in Combination With Acalabrutinib in
Subjects With Previously Untreated MCL. Available at:
https://clinicaltrials.gov/study/NCT02972840. Accessed January
2025.
7. 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.
8. Wu J, Zhang M, Liu D.
Acalabrutinib (ACP-196): a selective second-generation BTK
inhibitor. J Hematol
Oncol.
2016;9(21).
9. Data
on File, REF-236261. AstraZeneca Pharmaceuticals
LP.
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:
17 January 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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