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 2026
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.
Update on CARDIO-TTRansform Phase III trial
[This announcement contains inside information]
9 July 2026
Update on CARDIO-TTRansform Phase III
trial for Wainua (eplontersen) in adults with
transthyretin-mediated amyloid cardiomyopathy
The CARDIO-TTRansform Phase III trial1 for
AstraZeneca and Ionis' Wainua (eplontersen) in patients with
transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) did not
meet the primary efficacy endpoint of the composite outcome of
cardiovascular (CV) mortality and recurrent CV clinical events up
to 140 weeks compared with placebo. Wainua was generally well tolerated, with a safety
profile consistent with previous results.2
In this contemporary patient population treated with standard of
care, including a majority on a stabiliser,3,4 adding Wainua did
not provide a statistically significant benefit on the composite
outcome of CV mortality and recurrent CV events. In a prespecified
subgroup analysis of patients treated with Wainua monotherapy as compared to placebo, fewer
primary composite events (CV mortality and recurrent CV events)
were observed and this result was nominally significant. In
patients who were on stabiliser therapy at baseline, no treatment
effect was observed.
Sharon Barr, Executive Vice President, BioPharmaceuticals R&D,
said: "The CARDIO-TTRansform trial was designed to examine the role
of Wainua, a gene silencer treatment, on top of today's
standard of care in reducing recurring cardiovascular events and
mortality. Although the trial did not meet its primary objective,
we believe the results support greater scientific understanding of
treatment approaches for the hundreds of thousands of patients
worldwide suffering from this progressive and often fatal
condition."
CARDIO-TTRansform is a Phase III, multicentre, randomised,
double-blinded, placebo-controlled trial1 to
evaluate the safety and efficacy of Wainua compared to placebo in participants with
ATTR-CM receiving available standard of care: 57% of patients in
each arm received a stabiliser treatment at baseline, and a further
24% in each arm initiated a stabiliser during the
trial.3
AstraZeneca and Ionis will analyse the full data set to further
understand the results, which will be shared with the
scientific community at the European Society of Cardiology
(ESC) Congress in August 2026.
Notes
Transthyretin-Mediated Amyloid Cardiomyopathy
(ATTR-CM)
ATTR-CM is a systemic, progressive, debilitating and fatal disease
that predominantly affects the heart and is an underrecognised
cause of HF.5,6 ATTR-CM,
which can be inherited (hereditary, ATTRv) or develop with age
(wild-type, ATTRwt), occurs when amyloid fibrils consisting of
misfolded TTR protein build up in the heart, disrupting cardiac
structure and function and making it harder for the heart to pump
blood throughout the body.5-7 Patients
commonly present with non-specific symptoms such as shortness of
breath, swelling, heart palpitations, dizziness, weakness and
fatigue, which can contribute to misdiagnosis and delays in
care.5,7 With
an estimated 300,000 to 500,000 people living with ATTR-CM
worldwide,9 greater
awareness, earlier diagnosis and appropriate targeted treatment are
critical to improving outcomes and quality of life for
patients.10,11
CARDIO-TTRansform Trial
CARDIO-TTRansform is a global, randomised, double-blind,
placebo-controlled Phase III trial evaluating the efficacy and
safety of Wainua (eplontersen) in adults with wild-type or
hereditary ATTR-CM who are receiving available standard of
care.1,3,4 As
the largest enrolled ATTR-CM trial to date, CARDIO-TTRansform
enrolled 1,432 participants across 130 study sites in 20 countries,
who were randomised 1:1 to receive eplontersen 45 mg or placebo by
subcutaneous injection every four weeks.3 The
primary endpoint is a composite of CV mortality and recurrent CV
clinical events through Week 140.4 Secondary
endpoints include changes from baseline in the 6-minute walk test
and Kansas City Cardiomyopathy Questionnaire overall summary score
at Week 140, total recurrent CV clinical events up to Week 140,
all-cause mortality up to Weeks 140 and 160, the primary endpoint
in the subgroup of patients receiving a TTR stabiliser at baseline
and CV mortality through Weeks 140 and 160.4
Wainua (eplontersen)
Wainua is a once-monthly
RNA-targeted silencer that can be self-administered via an
autoinjector or as a pre-filled syringe by healthcare
professional administration in the US.12-14 It
provides upstream suppression of serum TTR production at its source
in the liver.12,13 Wainua has
now been approved for the treatment of the polyneuropathy of
hereditary transthyretin-mediated amyloidosis in adults, commonly
referred to as hATTR-PN or ATTRv-PN, in over 20 countries,
including in the EU as Wainzua.15
As part of a global development and commercialisation agreement,
AstraZeneca and Ionis are jointly developing and
commercialising Wainua in the US. Outside the US, AstraZeneca has
exclusive rest of world commercialisation and development
rights.
AstraZeneca in CVRM
Cardiovascular, Renal and Metabolism (CVRM), part of
BioPharmaceuticals, forms one of AstraZeneca's main disease areas
and is a key growth driver for the Company. By following the
science to understand more clearly the underlying links between the
heart, kidneys, liver and pancreas, AstraZeneca is investing in a
portfolio of medicines for organ protection by slowing or stopping
disease progression and ultimately paving the way towards
regenerative therapies. The Company's ambition is to improve and
save the lives of millions of people, by better understanding the
interconnections between CVRM diseases and targeting the mechanisms
that drive them, so we can detect, diagnose and treat people
earlier and more effectively.
AstraZeneca
AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development, and commercialisation of prescription medicines in
Oncology, Rare Disease, 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.
ClinicalTrials.gov.
CARDIO-TTRansform: A Study to Evaluate the Efficacy and Safety of
Eplontersen in Participants With Transthyretin-Mediated Amyloid
Cardiomyopathy (ATTR CM). Available at:
https://clinicaltrials.gov/study/NCT04136171. Accessed July
2026.
2.
AstraZeneca 2023.
Wainua (eplontersen) granted first-ever regulatory approval in the
US for the treatment of adults with polyneuropathy of hereditary
transthyretin-mediated amyloidosis. Available at:
https://www.astrazeneca.com/media-centre/press-releases/2023/astrazeneca-acquires-cincor-for-cardiorenal-asset.html.
Accessed July 2026.
3.
Maurer MS, et al.
Design and baseline characteristics of the CARDIO-TTRansform phase
3 randomised controlled trial of eplontersen for participants with
transthyretin amyloidosis with cardiomyopathy (ATTR-CM). Presented
at: Heart Failure Congress 2026. Heart Failure Congress 2026; 2026
9-12 May 2026; Barcelona, Spain.
4.
Masri A, et al.
Rationale and Design of CARDIO-TTRansform, a Phase 3 Trial of
Eplontersen in Transthyretin Amyloid Cardiomyopathy. Circulation: Heart Failure.
2026;19(6):e014205.
5.
Gertz MA.
Hereditary ATTR amyloidosis: burden of illness and diagnostic
challenges. Am J Manag
Care. 2017;23(7 Suppl):S107-s12.
6.
Ando Y, et al.
Guideline of transthyretin-related hereditary amyloidosis for
clinicians. Orphanet J Rare
Dis. 2013;8:31.
7.
Brunjes DL, et al.
Transthyretin Cardiac Amyloidosis in Older Americans. J Card Fail.
2016;22(12):996-1003.
8.
Rintell D, et al.
Patient and family experience with transthyretin amyloid
cardiomyopathy (ATTR-CM) and polyneuropathy (ATTR-PN) amyloidosis:
results of two focus groups. Orphanet J Rare Dis.
2021;16(1):70.
9.
Ionis
Pharmaceuticals I. SEC Filing Details 2022
10.
Kittleson MM, et
al. Transthyretin Cardiac Amyloidosis Evaluation and Management:
2025 ACC Concise Clinical Guidance. J Am Coll Cardiol.
2026;87(5):549-65.
11.
Maurer MS, et al.
Advancing Transthyretin Amyloidosis Drug Development in an Evolving
Treatment Landscape: Amyloidosis Forum Meeting Proceedings.
Adv Ther.
2024;41(7):2723-42.
12.
Coelho T, et al.
Design and Rationale of the Global Phase 3 NEURO-TTRansform Study
of Antisense Oligonucleotide AKCEA-TTR-L(Rx) (ION-682884-CS3) in
Hereditary Transthyretin-Mediated Amyloid Polyneuropathy. Neurol
Ther. 2021;10(1):375-89.
13.
Coelho T, et al.
Eplontersen for Hereditary Transthyretin Amyloidosis With
Polyneuropathy. JAMA. 2023;330(15):1448–1458.
14.
AstraZeneca. Wainua
(eplontersen) 45 mg solution for injection in pre-filled pen:
summary of product characteristics. European Medicines Agency. 2026
[Available from:
https://www.ema.europa.eu/en/documents/product-information/wainzua-epar-product-information_en.pdf.
15.
AstraZeneca 2024.
Wainzua (eplontersen) recommended for approval in the EU by CHMP
for the treatment of adult patients with polyneuropathy associated
with hereditary transthyretin-mediated amyloidosis. Available at:
https://www.astrazeneca.com/media-centre/press-releases/2024/wainzua-recommended-for-approval-in-the-eu.html.
Accessed July 2026.
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: 09 July 2026
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By: /s/
Matthew Bowden
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Name:
Matthew Bowden
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Title:
Company Secretary
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