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 2023
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
Indicate
by check mark whether the registrant files or will file annual
reports under cover of Form 20-F or Form 40-F.
Form
20-F X Form 40-F __
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(1):
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(7): ______
Indicate
by check mark whether the registrant by furnishing the information
contained in this Form is also thereby furnishing the information
to the Commission pursuant to Rule 12g3-2(b) under the Securities
Exchange Act of 1934.
Yes __
No X
If
“Yes” is marked, indicate below the file number
assigned to the Registrant in connection with Rule 12g3-2(b):
82-_____________
AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Discontinuation of two CRYSTALIZE evidence trials
1 December 2023
Update on CRYSTALIZE evidence trials
Discontinuation of STABILIZE-CKD and DIALIZE-Outcomes Phase III
trials
AstraZeneca has decided to discontinue the STABILIZE-CKD and
DIALIZE-Outcomes Phase III evidence trials
for Lokelma (sodium zirconium cyclosilicate). The
decision was made due to substantially increased enrolment
timelines and low event rates, respectively, which made it
prohibitive to deliver study results within a timeframe to
meaningfully advance clinical practice.
STABILIZE-CKD and DIALIZE-Outcomes trials are part of the
CRYSTALIZE evidence programme, which includes clinical and
real-world evidence studies researching the potential benefit
of Lokelma in the management of hyperkalaemia (HK)
across the cardiorenal spectrum.
Sharon Barr, Executive Vice President, BioPharmaceuticals R&D
said: "Our ambitious CRYSTALIZE programme continues to generate
evidence to improve the current management of hyperkalaemia, which
we believe leads to better outcomes for cardiorenal patients when a
potassium binder is included in their treatment
regimen. Lokelma is the leading branded potassium binder
globally and continues to benefit a broad hyperkalaemia patient
population to achieve rapid, sustained potassium control and is
well tolerated."
The Company will work with investigators to ensure the necessary
follow-up with patients.
Lokelma is approved for
the treatment of a broad HK patient population in 56 countries
worldwide. The decision to discontinue the trials is not due to
safety concerns and the positive benefit-risk
of Lokelma does not change in the approved
indication.
Notes
Hyperkalaemia
Hyperkalemia (HK) can be a chronic condition characterised by high
levels of potassium in the blood, generally defined as greater than
5 mmol/L.1,2 Patients
with high potassium levels are at significant risk of cardiac
arrhythmias, which can lead to cardiac arrest.3 Worldwide
there are about 840 million and 64 million people living with CKD
and HF respectively, who are at an estimated two to three times
higher risk of hyperkalemia.4-7 RAASi
therapy is guideline-recommended to slow down CKD progression and
reduce CV events, but the dose is often lowered or therapy is
discontinued when HK is diagnosed.8-11 This
has been shown to negatively impact patient outcomes, with
mortality rates doubled for patients with CKD and HF whose RAASi
had been down-titrated or discontinued compared to patients on
maximum RAASi dose.12
STABILIZE-CKD
STABILIZE-CKD is a Phase III randomised double-blind,
placebo-controlled, multicentre study evaluating the effect
of Lokelma, as an adjunct to optimised RAASi therapy
(ACEi/ARB) on CKD progression in participants with CKD and HK
or at-risk of HK.13 The
study consists of a three-month up-titration period with an
ACEi/ARB to guideline-recommended doses while
taking Lokelma followed by
a maintenance phase of two years with repeated estimated
glomerular filtration rate (eGFR) measurements, originally planned
to involve 1360 participants across the
world.
DIALIZE-Outcomes
DIALIZE-Outcomes is a Phase III randomised, double-blind,
placebo-controlled, multicentre study evaluating the effect
of Lokelma on arrhythmia-related cardiovascular
outcomes in patients on chronic haemodialysis with recurrent
HK.14 The
study involves approximately 2800 participants across the
world.
Lokelma
Lokelma (sodium zirconium cyclosilicate) is an
anti-hyperkalaemia (HK) therapy that provides rapid potassium
reduction and sustained potassium control.15 It
is indicated for the treatment of HK in adults, including patients
with ESKD on chronic haemodialysis.16 It
is an insoluble, non-absorbed sodium zirconium silicate, formulated
as a powder for oral suspension, that acts as a highly selective
potassium-removing medicine.16 It
is administered orally and is odourless, tasteless, and stable at
room temperature.16-17 Lokelma has
been approved in more than 56 countries including US, EU, China and
Japan.18
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/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 social media @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1.
Thomsen RW et al. Elevated Potassium levels in
patients with chronic kidney disease; occurrence, risk factors and
clinical outcomes - a Danish population-based cohort
study. J Am Heart
Assoc.
2018;7:e008912
2.
Kovesdy CP, et al.Management of hyperkalaemia in
chronic kidney disease. Nat Rev
Nephrol. Nov
2014;10:653-662
3.
Kovesdy CP, et al. Serum and Dialysate Potassium
Concentrations and Survival in Hemodialysis
Patients. Clin J Am Soc
Nephrol.
2007:2:999-1007.
4.
Jain N, et al. Predictors of hyperkalemia and
death in patients with cardiac and renal
disease. Am J
Cardiol.
2012;109(10):1510-1513.
5.
Sarwar, et al. Hyperkalemia in Heart
Failure. J Am Coll
Cardiol.
2016;68(14):1575-1589.
6.
Jager KJ, et al. A Single Number for Advocacy and
Communication-Worldwide More than 850 Million Individuals Have
Kidney Diseases. Nephrol Dial
Transplant.
2019;34(11):1803-5.
7.
Vos T, et al. Global, regional, and national
incidence, prevalence, and years lived with disability for 328
diseases and injuries for 195 countries, 1990-2016: A systematic
analysis for the Global Burden of Disease Study
2016. The Lancet 2017;
390(10100):1211-59.
8.
McDonagh TA, et al. 2021 ESC guidelines for the
diagnosis and treatment of acute and chronic heart
failure. Eur Heart J. 2021;42(36):3599-3726.
9.
Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022
AHA/ACC/HFSA Guideline for the Management of Heart Failure: A
Report of the American College of Cardiology/American Heart
Association Joint Committee on Clinical Practice
Guidelines. J Am Coll
Cardiol.
2022;79(17):e263-e421.
10.
Collins AJ, et al. Association of serum potassium
with all-cause mortality in patients with and without heart
failure, chronic kidney disease, and/or
diabetes. Am J
Nephrol.
2017;46(3):213-221.
11.
Kidney
Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group.
Kidney Int. 2022;102(5S): S1-S127.
12.
Epstein et al. Evaluation of the Treatment Gap
Between Clinical Guidelines and the Utilization of
Renin-Angiotensin Aldosterone System
Inhibitors. Am J Manag
Care. 2015;21(11 suppl):
S212-S220.
13.
ClinicalTrials.Gov: A Study to
Evaluate the Effect of Sodium Zirconium Cyclosilicate on Chronic
Kidney Disease (CKD) Progression in Participants With CKD and
Hyperkalaemia or at Risk of Hyperkalaemia (STABILIZE-CKD).
Available at: https://clinicaltrials.gov/study/NCT05056727?intr=lokelma&rank=7.
Last accessed November 2023.
14.
ClinicalTrials.Gov: Effect of
Sodium Zirconium Cyclosilicate on Arrythmia-related Cardiovascular
Outcomes in Participants on Chronic Hemodialysis With Recurrent
Hyperkalemia (DIALIZE-Outcomes). Available at: https://clinicaltrials.gov/study/NCT04847232?intr=lokelma&rank=6.
Last accessed November 2023.
15.
Kosiborod M, et al. Effect of sodium
zirconium cyclosilicate on potassium lowering for 28 days among
outpatients with hyperkalemia: the HARMONIZE randomized clinical
trial [article and protocol]. JAMA. 2014;312:2223-2233.
16.
European Medicines Agency
[Internet] Lokelma (sodium
zirconium cyclosilicate). Summary of Product Characteristics;
[cited 12 Oct 2023]. Available at: https://www.ema.europa.eu/en/documents/product-information/lokelma-epar-product-information_en.pdf.
Last accessed November 2023
17.
Lokelma® (sodium zirconium
cyclosilicate) for oral suspension [Internet]. US prescribing
information. Wilmington (DE): AstraZeneca Pharmaceuticals LP;
[cited 12 Oct 2023]. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/207078s003lbl.pdf.
Last accessed November 2023.
18.
AstraZeneca.
Data on file. [REF-198643]
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: 1
December 2023
|
|
By: /s/
Adrian Kemp
|
|
|
Name:
Adrian Kemp
|
|
|
Title:
Company Secretary
|
AstraZeneca (PK) (USOTC:AZNCF)
Historical Stock Chart
From Dec 2024 to Jan 2025
AstraZeneca (PK) (USOTC:AZNCF)
Historical Stock Chart
From Jan 2024 to Jan 2025
