<SEC-DOCUMENT>0001654954-23-015010.txt : 20231201
<SEC-HEADER>0001654954-23-015010.hdr.sgml : 20231201
<ACCEPTANCE-DATETIME>20231201062636
ACCESSION NUMBER:		0001654954-23-015010
CONFORMED SUBMISSION TYPE:	6-K
PUBLIC DOCUMENT COUNT:		1
CONFORMED PERIOD OF REPORT:	20231201
FILED AS OF DATE:		20231201
DATE AS OF CHANGE:		20231201

FILER:

	COMPANY DATA:	
		COMPANY CONFORMED NAME:			ASTRAZENECA PLC
		CENTRAL INDEX KEY:			0000901832
		STANDARD INDUSTRIAL CLASSIFICATION:	PHARMACEUTICAL PREPARATIONS [2834]
		IRS NUMBER:				000000000
		STATE OF INCORPORATION:			X0
		FISCAL YEAR END:			1231

	FILING VALUES:
		FORM TYPE:		6-K
		SEC ACT:		1934 Act
		SEC FILE NUMBER:	001-11960
		FILM NUMBER:		231457475

	BUSINESS ADDRESS:	
		STREET 1:		1 FRANCIS CRICK AVENUE
		STREET 2:		CAMBRIDGE BIOMEDICAL CAMPUS
		CITY:			CAMBRIDGE
		STATE:			X0
		ZIP:			CB2 0AA
		BUSINESS PHONE:		011 44 20 7304 5000

	MAIL ADDRESS:	
		STREET 1:		1 FRANCIS CRICK AVENUE
		STREET 2:		CAMBRIDGE BIOMEDICAL CAMPUS
		CITY:			CAMBRIDGE
		STATE:			X0
		ZIP:			CB2 0AA

	FORMER COMPANY:	
		FORMER CONFORMED NAME:	ZENECA GROUP PLC
		DATE OF NAME CHANGE:	19930422
</SEC-HEADER>
<DOCUMENT>
<TYPE>6-K
<SEQUENCE>1
<FILENAME>a2725v.htm
<DESCRIPTION>DISCONTINUATION OF TWO CRYSTALIZE EVIDENCE TRIALS
<TEXT>
<html>
<head>
<!-- Document created using Blueprint(R) - powered by Issuer Direct - www.issuerdirect.com -->
<!-- Copyright 2023 Issuer Direct Corporation -->
<title>a2725v</title>
</head>
<body style="font-family: Times New Roman; font-size: 13px;">
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; font-family: Times New Roman; font-size: 13px">
FORM 6-K</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">SECURITIES
AND EXCHANGE COMMISSION</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">Washington,
D.C. 20549</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">Report
of Foreign Issuer</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">Pursuant
to Rule 13a-16 or 15d-16 of</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">the
Securities Exchange Act of 1934</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">For the
month of December 2023</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">Commission
File Number: 001-11960</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; font-family: Times New Roman; font-size: 13px">
AstraZeneca PLC</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">1
Francis Crick Avenue</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">Cambridge
Biomedical Campus</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">Cambridge
CB2 0AA</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">United
Kingdom</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">Indicate
by check mark whether the registrant files or will file annual
reports under cover of Form 20-F or Form 40-F.</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">Form
20-F X Form 40-F __</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">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):</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">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): ______</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">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.</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">Yes __
No X</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">If
&#x201C;Yes&#x201D; is marked, indicate below the file number
assigned to the Registrant in connection with Rule 12g3-2(b):
82-_____________</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; font-family: Times New Roman; font-size: 13px">
AstraZeneca PLC</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">INDEX
TO EXHIBITS</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="margin-left: 24px; display: table">
<div style="display: table-row">
<div style="text-align: left; display: table-cell; width: 24px">
<font style="font-weight: bold; font-style: italic; font-family: Times New Roman; font-size: 13px">
1.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-weight: bold; font-style: italic; font-family: Times New Roman; font-size: 13px">
Discontinuation of two CRYSTALIZE evidence trials</font></div>
</div>
</div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
1 December 2023</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
Update on&#xA0;CRYSTALIZE&#xA0;evidence trials</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; font-style: italic; color: #000000; font-family: Times New Roman; font-size: 13px">
Discontinuation of STABILIZE-CKD and DIALIZE-Outcomes Phase III
trials</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
AstraZeneca has decided to discontinue the STABILIZE-CKD and
DIALIZE-Outcomes Phase III evidence trials
for&#xA0;</font><font style="font-style: italic; color: #000000">Lokelma</font><font style="color: #000000">&#xA0;(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.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
STABILIZE-CKD and DIALIZE-Outcomes trials are part of the
CRYSTALIZE evidence programme, which&#xA0;includes clinical and
real-world evidence studies researching the potential benefit
of&#xA0;</font><font style="font-style: italic; color: #000000">Lokelma</font><font style="color: #000000">&#xA0;in the management of hyperkalaemia (HK)
across the cardiorenal spectrum.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
Sharon Barr, Executive Vice President, BioPharmaceuticals R&amp;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.&#xA0;</font><font style="font-style: italic; color: #000000">Lokelma</font><font style="color: #000000">&#xA0;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."</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
The Company will work with investigators to ensure the necessary
follow-up with patients.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic; color: #000000">
Lokelma</font><font style="color: #000000">&#xA0;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&#xA0;</font><font style="font-style: italic; color: #000000">Lokelma</font><font style="color: #000000">&#xA0;does not change in the approved
indication.&#xA0;</font></font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="text-decoration: underline; color: #000000; font-weight: bold; font-family: Times New Roman; font-size: 13px">
Notes</font></div>
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
Hyperkalaemia</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
Hyperkalemia (HK) can be a chronic condition characterised by high
levels of potassium in the blood, generally defined as greater than
5 mmol/L.</font><font style="font-size: 70%; vertical-align: top; color: #000000">1,2</font><font style="color: #000000">&#xA0;Patients
with high potassium levels are at significant risk of cardiac
arrhythmias, which can lead to cardiac arrest.</font><font style="font-size: 70%; vertical-align: top; color: #000000">3</font><font style="color: #000000">&#xA0;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.</font><font style="font-size: 70%; vertical-align: top; color: #000000">4-7</font><font style="color: #000000">&#xA0;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.</font><font style="font-size: 70%; vertical-align: top; color: #000000">8-11</font><font style="color: #000000">&#xA0;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.</font><font style="font-size: 70%; vertical-align: top; color: #000000">12</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
STABILIZE-CKD</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
STABILIZE-CKD is a Phase III randomised double-blind,
placebo-controlled, multicentre study evaluating the effect
of&#xA0;</font><font style="font-style: italic; color: #000000">Lokelma</font><font style="color: #000000">, as an adjunct to optimised RAASi therapy
(ACEi/ARB)</font><font style="font-style: italic; color: #000000">&#xA0;</font><font style="color: #000000">on CKD progression in participants with CKD and HK
or at-risk of HK.</font><font style="font-size: 70%; vertical-align: top; color: #000000">13</font><font style="color: #000000">&#xA0;The
study consists of a three-month up-titration period&#xA0;with an
ACEi/ARB&#xA0;to guideline-recommended doses while
taking&#xA0;</font><font style="font-style: italic; color: #000000">Lokelma&#xA0;</font><font style="color: #000000">followed&#xA0;by
a maintenance phase of&#xA0;two years&#xA0;with repeated estimated
glomerular filtration rate (eGFR) measurements, originally planned
to&#xA0;involve 1360&#xA0;participants&#xA0;across&#xA0;the
world.</font></font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
DIALIZE-Outcomes</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
DIALIZE-Outcomes is a Phase III randomised, double-blind,
placebo-controlled, multicentre study evaluating the effect
of&#xA0;</font><font style="font-style: italic; color: #000000">Lokelma</font><font style="color: #000000">&#xA0;on arrhythmia-related cardiovascular
outcomes in patients on chronic haemodialysis with recurrent
HK.</font><font style="font-size: 70%; vertical-align: top; color: #000000">14</font><font style="font-weight: bold; color: #000000">&#xA0;</font><font style="color: #000000">The
study involves approximately 2800 participants across the
world.</font></font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; font-style: italic; color: #000000; font-family: Times New Roman; font-size: 13px">
Lokelma</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic; color: #000000">
Lokelma</font><font style="font-weight: bold; color: #000000">&#xA0;</font><font style="color: #000000">(sodium zirconium cyclosilicate) is an
anti-hyperkalaemia (HK) therapy that provides rapid potassium
reduction and sustained potassium control</font><font style="color: #FF0000">.</font><font style="font-size: 70%; vertical-align: top; color: #000000">15</font><font style="font-weight: bold; color: #000000">&#xA0;</font><font style="color: #000000">It
is indicated for the treatment of HK in adults, including patients
with ESKD on chronic haemodialysis.</font><font style="font-size: 70%; vertical-align: top; color: #000000">16</font><font style="color: #000000">&#xA0;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.</font><font style="font-size: 70%; vertical-align: top; color: #000000">16</font><font style="color: #000000">&#xA0;It
is administered orally and is odourless, tasteless, and stable at
room temperature.</font><font style="font-size: 70%; vertical-align: top; color: #000000">16-17</font><font style="color: #000000">&#xA0;</font><font style="font-style: italic; color: #000000">Lokelma</font><font style="color: #000000">&#xA0;has
been approved in more than 56 countries including US, EU, China and
Japan.</font><font style="font-size: 70%; vertical-align: top; color: #000000">18</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; font-family: Times New Roman; font-size: 13px">
<font style="color: #000000">AstraZeneca
in&#xA0;</font><font style="text-decoration: underline; color: #0000FF">CVRM</font><font style="color: #000000">&#xA0;</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
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.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="text-decoration: underline; color: #0000FF; font-weight: bold; font-family: Times New Roman; font-size: 13px">
AstraZeneca</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
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 &amp; Metabolism, and Respiratory &amp;
Immunology. Based in Cambridge, UK, AstraZeneca operates in over
100 countries and its innovative medicines are used by millions of
patients worldwide. Please visit&#xA0;</font><font style="text-decoration: underline; color: #0000FF">astrazeneca.com</font><font style="color: #000000">&#xA0;and
follow the Company on social media&#xA0;</font><font style="text-decoration: underline; color: #0000FF">@AstraZeneca.</font></font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
Contacts</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
For details on how to contact the Investor Relations Team, please
click&#xA0;</font><font style="text-decoration: underline; color: #0000FF">here</font><font style="color: #000000">.
For Media contacts, click&#xA0;</font><font style="text-decoration: underline; color: #0000FF">here</font><font style="color: #000000">.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
References</font></div>
<div style="margin-left: 0px; display: table">
<div style="display: table-row">
<div style="text-align: left; display: table-cell; width: 24px">
<font style="color: #000000; font-size: 13px; font-family: Times New Roman">1.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">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.&#xA0;</font><font style="font-style: italic; color: #000000">J Am Heart
Assoc</font><font style="color: #000000">.
2018;7:e008912</font></font></div>
</div>
</div>
<div style="margin-left: 0px; display: table">
<div style="display: table-row">
<div style="text-align: left; display: table-cell; width: 24px">
<font style="color: #000000; font-size: 13px; font-family: Times New Roman">2.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">Kovesdy CP, et al.Management of hyperkalaemia in
chronic kidney disease.&#xA0;</font><font style="font-style: italic; color: #000000">Nat Rev
Nephrol</font><font style="color: #000000">. Nov
2014;10:653-662</font></font></div>
</div>
</div>
<div style="margin-left: 0px; display: table">
<div style="display: table-row">
<div style="text-align: left; display: table-cell; width: 24px">
<font style="color: #000000; font-size: 13px; font-family: Times New Roman">3.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">Kovesdy CP, et al. Serum and Dialysate Potassium
Concentrations and Survival in Hemodialysis
Patients.&#xA0;</font><font style="font-style: italic; color: #000000">Clin J Am Soc
Nephrol</font><font style="color: #000000">.
2007:2:999-1007.</font></font></div>
</div>
</div>
<div style="margin-left: 0px; display: table">
<div style="display: table-row">
<div style="text-align: left; display: table-cell; width: 24px">
<font style="color: #000000; font-size: 13px; font-family: Times New Roman">4.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">Jain N, et al. Predictors of hyperkalemia and
death in patients with cardiac and renal
disease.&#xA0;</font><font style="font-style: italic; color: #000000">Am J
Cardiol</font><font style="color: #000000">.
2012;109(10):1510-1513.</font></font></div>
</div>
</div>
<div style="margin-left: 0px; display: table">
<div style="display: table-row">
<div style="text-align: left; display: table-cell; width: 24px">
<font style="color: #000000; font-size: 13px; font-family: Times New Roman">5.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">Sarwar, et al. Hyperkalemia in Heart
Failure.&#xA0;</font><font style="font-style: italic; color: #000000">J Am Coll
Cardiol</font><font style="color: #000000">.
2016;68(14):1575-1589.</font></font></div>
</div>
</div>
<div style="margin-left: 0px; display: table">
<div style="display: table-row">
<div style="text-align: left; display: table-cell; width: 24px">
<font style="color: #000000; font-size: 13px; font-family: Times New Roman">6.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">Jager KJ, et al. A Single Number for Advocacy and
Communication-Worldwide More than 850 Million Individuals Have
Kidney Diseases.&#xA0;</font><font style="font-style: italic; color: #000000">Nephrol Dial
Transplant</font><font style="color: #000000">.
2019;34(11):1803-5.</font></font></div>
</div>
</div>
<div style="margin-left: 0px; display: table">
<div style="display: table-row">
<div style="text-align: left; display: table-cell; width: 24px">
<font style="color: #000000; font-size: 13px; font-family: Times New Roman">7.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">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.&#xA0;</font><font style="font-style: italic; color: #000000">The Lancet</font><font style="color: #000000">&#xA0;2017;
390(10100):1211-59.</font></font></div>
</div>
</div>
<div style="margin-left: 0px; display: table">
<div style="display: table-row">
<div style="text-align: left; display: table-cell; width: 24px">
<font style="color: #000000; font-size: 13px; font-family: Times New Roman">8.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">McDonagh TA, et al. 2021 ESC guidelines for the
diagnosis and treatment of acute and chronic heart
failure.&#xA0;</font><font style="font-style: italic; color: #000000">Eur Heart J</font><font style="color: #000000">. 2021;42(36):3599-3726.</font></font></div>
</div>
</div>
<div style="margin-left: 0px; display: table">
<div style="display: table-row">
<div style="text-align: left; display: table-cell; width: 24px">
<font style="color: #000000; font-size: 13px; font-family: Times New Roman">9.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">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.&#xA0;</font><font style="font-style: italic; color: #000000">J Am Coll
Cardiol</font><font style="color: #000000">.
2022;79(17):e263-e421.</font></font></div>
</div>
</div>
<div style="margin-left: 0px; display: table">
<div style="display: table-row">
<div style="text-align: left; display: table-cell; width: 24px">
<font style="color: #000000; font-size: 13px; font-family: Times New Roman">10.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">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.&#xA0;</font><font style="font-style: italic; color: #000000">Am J
Nephrol</font><font style="color: #000000">.
2017;46(3):213-221.</font></font></div>
</div>
</div>
<div style="margin-left: 0px; display: table">
<div style="display: table-row">
<div style="text-align: left; display: table-cell; width: 24px">
<font style="color: #000000; font-size: 13px; font-family: Times New Roman">11.</font></div>
<div style="text-align: justify; display: table-cell"><font style="color: #000000; font-family: Times New Roman; font-size: 13px">Kidney
Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group.
Kidney Int. 2022;102(5S): S1-S127.</font></div>
</div>
</div>
<div style="margin-left: 0px; display: table">
<div style="display: table-row">
<div style="text-align: left; display: table-cell; width: 24px">
<font style="color: #000000; font-size: 13px; font-family: Times New Roman">12.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">Epstein et al. Evaluation of the Treatment Gap
Between Clinical Guidelines and the Utilization of
Renin-Angiotensin Aldosterone System
Inhibitors.&#xA0;</font><font style="font-style: italic; color: #000000">Am J Manag
Care</font><font style="color: #000000">. 2015;21(11 suppl):
S212-S220.</font></font></div>
</div>
</div>
<div style="margin-left: 0px; display: table">
<div style="display: table-row">
<div style="text-align: left; display: table-cell; width: 24px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">13.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000; font-size: 13px">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:</font><font style="color: #000000">&#xA0;</font><font style="text-decoration: underline; color: #0000FF; font-size: 13px">https://clinicaltrials.gov/study/NCT05056727?intr=lokelma&amp;rank=7</font><font style="color: #000000; font-size: 13px">.
Last accessed November 2023.</font></font></div>
</div>
</div>
<div style="margin-left: 0px; display: table">
<div style="display: table-row">
<div style="text-align: left; display: table-cell; width: 24px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">14.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000; font-size: 13px">ClinicalTrials.Gov: Effect of
Sodium Zirconium Cyclosilicate on Arrythmia-related Cardiovascular
Outcomes in Participants on Chronic Hemodialysis With Recurrent
Hyperkalemia (DIALIZE-Outcomes). Available at:</font><font style="color: #000000">&#xA0;</font><font style="text-decoration: underline; color: #0000FF; font-size: 13px">https://clinicaltrials.gov/study/NCT04847232?intr=lokelma&amp;rank=6</font><font style="color: #000000; font-size: 13px">.
Last accessed November 2023.</font></font></div>
</div>
</div>
<div style="margin-left: 0px; display: table">
<div style="display: table-row">
<div style="text-align: left; display: table-cell; width: 24px">
<font style="color: #000000; font-size: 13px; font-family: Times New Roman">15.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">Kosiborod M, et al.&#xA0; Effect of sodium
zirconium cyclosilicate on potassium lowering for 28 days among
outpatients with hyperkalemia: the HARMONIZE randomized clinical
trial [article and protocol].&#xA0;</font><font style="font-style: italic; color: #000000">JAMA</font><font style="color: #000000">. 2014;312:2223-2233.</font></font></div>
</div>
</div>
<div style="margin-left: 0px; display: table">
<div style="display: table-row">
<div style="text-align: left; display: table-cell; width: 24px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">16.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000; font-size: 13px">European Medicines Agency
[Internet]&#xA0;</font><font style="font-style: italic; color: #000000; font-size: 13px">Lokelma</font><font style="color: #000000; font-size: 13px">&#xA0;(sodium
zirconium cyclosilicate). Summary of Product Characteristics;
[cited 12 Oct 2023]. Available at:&#xA0;</font><font style="color: #000000">&#xA0;</font><font style="text-decoration: underline; color: #0000FF; font-size: 13px">https://www.ema.europa.eu/en/documents/product-information/lokelma-epar-product-information_en.pdf.
Last accessed November 2023</font></font></div>
</div>
</div>
<div style="margin-left: 0px; display: table">
<div style="display: table-row">
<div style="text-align: left; display: table-cell; width: 24px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">17.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000; font-size: 13px">Lokelma&#xAE; (sodium zirconium
cyclosilicate) for oral suspension [Internet]. US prescribing
information. Wilmington (DE): AstraZeneca Pharmaceuticals LP;
[cited 12 Oct 2023]. Available at:</font><font style="color: #000000">&#xA0;</font><font style="text-decoration: underline; color: #0000FF; font-size: 13px">https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/207078s003lbl.pdf.
Last accessed November 2023</font><font style="color: #000000; font-size: 13px">.</font></font></div>
</div>
</div>
<div style="margin-left: 0px; display: table">
<div style="display: table-row">
<div style="text-align: left; display: table-cell; width: 24px">
<font style="color: #000000; font-size: 13px; font-family: Times New Roman">18.</font></div>
<div style="text-align: justify; display: table-cell"><font style="color: #000000; font-family: Times New Roman; font-size: 13px">AstraZeneca.
Data on file. [REF-198643]</font></div>
</div>
</div>
<div style="text-align: left; margin-left: 120px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px;">&#xA0;</font></div>
<div style="text-align: left; margin-left: 120px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px;">&#xA0;</font></div>
<div style="text-align: left; margin-left: 120px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
Adrian Kemp</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
Company Secretary</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
AstraZeneca PLC</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-style: italic; color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="text-decoration: underline; font-family: Times New Roman; font-size: 13px">
SIGNATURES</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">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.</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div>
<table cellpadding="0" cellspacing="0" style="width: 100%; font-family: Times New Roman; font-size: 13px">
<tr>
<td style="vertical-align: top; width: 71%">
<div><font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
</td>
<td style="vertical-align: top; width: 29%">
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">AstraZeneca
PLC</font></div>
</td>
</tr></table>
</div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">Date: 1
December 2023</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div>
<table cellpadding="0" cellspacing="0" style="width: 100%; font-family: Times New Roman; font-size: 13px">
<tr>
<td style="vertical-align: top; width: 71%">
<div><font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
</td>
<td style="vertical-align: top; width: 29%">
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">By: /s/
Adrian Kemp</font></div>
</td>
</tr><tr>
<td style="vertical-align: top; width: 71%">
<div><font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
</td>
<td style="vertical-align: top; width: 29%">
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">Name:
Adrian Kemp</font></div>
</td>
</tr><tr>
<td style="vertical-align: top; width: 71%">
<div><font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
</td>
<td style="vertical-align: top; width: 29%">
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">Title:
Company Secretary</font></div>
</td>
</tr></table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
</SEC-DOCUMENT>
