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 July 2025
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.
Update on anselamimab in AL amyloidosis
16 July
2025
Update on CARES Phase III clinical programme of anselamimab in
light chain amyloidosis
Results did not achieve statistical significance for the primary
endpoint in overall patient population
Anselamimab showed highly
clinically meaningful improvement vs. placebo in survival and
cardiovascular hospitalisation in prespecified patient
subgroup
High-level results from the Cardiac Amyloid Reaching for Extended
Survival (CARES) Phase III clinical programme showed that
anselamimab, a light chain depleter antibody, did not achieve
statistical significance for the primary
endpoint compared to placebo in patients with Mayo stages
IIIa and IIIb light chain (AL) amyloidosis. The primary endpoint
was defined as a hierarchical combination of time to all-cause
mortality (ACM) and frequency of cardiovascular hospitalisations
(CVH). All patients in the clinical programme received background
standard of care for plasma cell dyscrasia.
Anselamimab showed highly clinically meaningful improvement in time
to ACM and frequency of CVH in a prespecified subgroup of patients,
compared to placebo.
AL amyloidosis is a rare, systemic and progressive disorder caused
by defective plasma cells in the bone marrow. In AL amyloidosis,
abnormal light chain proteins produced by these plasma cells
misfold, aggregate and form amyloid fibrils that deposit in tissues
and organs. Left untreated, the accumulation of these toxic amyloid
deposits, particularly in the heart and kidneys, can cause
progressive organ damage and dysfunction and may lead to premature
death, most commonly due to cardiac failure.1-3
Ashutosh Wechalekar, MBBS, MD, FRCP, FRCPath, DM, Consultant
Haematologist at University College London Hospitals NHS Foundation
Trust (UCLH), Professor of Medicine and Haematology at University
College London (UCL) and lead principal investigator of the
programme, said: "While the study did not meet the primary endpoint
in the overall patient population, results from a pre-defined
subgroup suggest that anselamimab, by targeting and clearing
amyloid deposits, may address a leading cause of organ damage and
functional impairment in these patients. The potential to extend
survival and reduce cardiovascular hospitalisations would represent
a practice-changing advancement for this patient
group."
Marc Dunoyer, Chief Executive Officer, Alexion, AstraZeneca Rare
Disease, said: "Alexion is pioneering a novel mechanism of action
to address organ damage from existing amyloid deposits in patients
with AL amyloidosis, a devastating disease often diagnosed in
advanced stages with poor prognosis. Anselamimab is the first and
only investigational fibril depleter to show clinical benefit in AL
amyloidosis, and these results underscore its potential to address
a critical treatment gap in a prespecified subgroup of
patients."
Anselamimab was well tolerated, with the majority of events
balanced between the anselamimab treatment arm and the placebo
arm.
Evaluation of full results is ongoing to further characterise the
efficacy and safety of anselamimab. Alexion plans
to share these data with global health authorities
and present them at a forthcoming medical
meeting.
Notes
Light Chain amyloidosis
Light chain (AL) amyloidosis is a systemic and progressive type of
amyloidosis where immunoglobulin light chain proteins are produced
abnormally by defective plasma cells in the bone marrow. These
abnormal proteins misfold, aggregate and form amyloid fibrils that
deposit and accumulate in tissues or organs, particularly in the
heart and kidneys. The deposition can cause progressive damage and
may lead to premature death, most commonly due to cardiac
failure.1,2
In the early stages of the disease, people with AL amyloidosis may
experience a range of vague signs and symptoms that mimic other
diseases, which can often delay the diagnosis. Worldwide, there are
an estimated 74,000 patients living with AL
amyloidosis.4,5
CARES Phase III Clinical Programme
The Cardiac Amyloid Reaching for Extended Survival (CARES) clinical
programme consists of two parallel global, Phase III, randomised,
double-blind, placebo-controlled, multicentre trials evaluating the
efficacy and safety of anselamimab plus standard of care (SoC) in
patients with stage IIIa and stage IIIb light chain (AL)
amyloidosis, respectively.6,7
The primary endpoint is a hierarchical combination of time to
all-cause mortality and frequency of cardiovascular
hospitalisations in the overall patient population across both
trials.
The CARES clinical programme is the largest prospective
investigation in cardiac AL amyloidosis to date with a total of 406
patients enrolled from 19 countries globally, including 281
patients with stage IIIa and 125 patients with stage IIIb disease
per European modification of the Mayo 2004 staging
system.6,7
In CARES, newly diagnosed patients planning first-line plasma cell
dyscrasia (PCD) treatment with cyclophosphamide, bortezomib and
dexamethasone were randomised 2:1 to receive either anselamimab or
placebo once weekly for the first four weeks and then every two
weeks until study completion. Daratumumab was permitted but not
required as part of the PCD regimen, and approximately 80% of
patients in CARES received daratumumab as part of their
treatment.
Following the primary evaluation treatment period, which concluded
18 months after the last patient was randomised, all patients had
the option to participate in an open-label extension period
receiving anselamimab plus SoC for up to 24
months.6,7
Anselamimab
Anselamimab is an investigational, potentially first-in-class
anti-fibril monoclonal antibody designed to improve organ function
by reducing or eliminating amyloid deposits in the tissues and
organs of patients living with AL amyloidosis. By binding with
specificity to targets within amino acids on misfolded amyloid
fibrils, anselamimab promotes destruction and clearance of amyloid
deposits, while sparing native free light chains from destruction.
Anselamimab has been granted Fast Track Designation by the US Food
and Drug Administration (FDA) and received Orphan Drug Designation
from the US FDA, European Commission and the Ministry of Health,
Labour and Welfare of Japan for the treatment of AL
amyloidosis.
Alexion
Alexion, AstraZeneca Rare Disease, is focused on serving patients
and families affected by rare diseases and devastating conditions
through the discovery, development and delivery of life-changing
medicines. A pioneering leader in rare disease for more than three
decades, Alexion was the first to translate the complex biology of
the complement system into transformative medicines, and today it
continues to build a diversified pipeline across disease areas with
significant unmet need, using an array of innovative modalities. As
part of AstraZeneca, Alexion is continually expanding its global
geographic footprint to serve more rare disease patients around the
world. It is headquartered in Boston, US.
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. Desport E, et al. AL
Amyloidosis. Orphanet J
Rare Dis.
2012;7(54).
2. Grogan M, et al. Light-chain
cardiac amyloidosis: strategies to promote early diagnosis and
cardiac response. Heart.
2017;103:1065-1072.
3. Mollee P, et al. How to diagnose
amyloidosis. Internal
Medicine Journal. 2014;44:7-17.
4. Wechalekar AD, et al. AL
Amyloidosis for Cardiologists; Awareness, Diagnosis, and Future
Prospects. JACC:
CardioOncology. 2022;4(4): 427-
441.
5. Kumar N, et al. Global
epidemiology of amyloid light-chain
amyloidosis. Orphanet J
Rare Dis.
2022;17(278).
6. ClinicalTrials.gov. A Study to
Evaluate the Efficacy and Safety of CAEL-101 in Patients With Mayo
Stage IIIa AL Amyloidosis (CARES). NCT Identifier:
NCT04512235. Available here.
Accessed June 2025.
7. ClinicalTrials.gov. A Study to
Evaluate the Efficacy and Safety of CAEL-101 in Patients With Mayo
Stage IIIb AL Amyloidosis (CARES). NCT Identifier:
NCT04504825. Available here.
Accessed June 2025.
Matthew Bowden
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:
16 July 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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