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 October 2025
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.
Baxdrostat met primary endpoint in Bax24 Ph3 trial
7 October
2025
Baxdrostat met the primary endpoint in Bax24 Phase III trial in
patients with resistant hypertension
Baxdrostat demonstrated a statistically significant and highly
clinically meaningful reduction in 24-hour ambulatory systolic
blood pressure compared with placebo
Positive high-level results from the Bax24 Phase III trial showed
baxdrostat demonstrated a statistically significant and highly
clinically meaningful reduction in ambulatory 24-hour average
systolic blood pressure (SBP) compared with placebo at 12 weeks.
Efficacy was observed throughout the 24-hour period, including
early morning, when patients with hypertension are at a higher risk
of cardiovascular events.1-3
Patients with treatment-resistant hypertension (rHTN) received
baxdrostat 2mg or placebo on top of standard of care. Baxdrostat
was generally well tolerated, with a safety profile consistent with
the BaxHTN trial.4
There are 1.4 billion people worldwide living with
hypertension.5 In
the US, approximately 50% of patients living with hypertension on
multiple treatments do not have their blood pressure under
control.6 Consistent
24-hour blood pressure control is an important clinical outcome in
patients with hard-to-control hypertension.7-9 Multiple
studies have demonstrated that 24-hour blood pressure is a more
powerful predictor of cardiovascular events than a clinic-based
measurement.3,10 When
24-hour average systolic blood pressure rises by 9.5 mmHg, the risk
of all-cause mortality increases by 30%.3
Dr. Bryan Williams, Chair of Medicine at University College London,
primary investigator, said: "The Bax24 results show that a
once-daily baxdrostat regimen can deliver highly clinically
meaningful reductions in 24-hour systolic blood pressure, including
in the morning when patients are at greater risk of heart attack
and stroke. These results are groundbreaking and together with the
BaxHTN results mean we have the potential to change our treatment
approach for the many patients whose hypertension remains
uncontrolled despite current therapies."
Sharon Barr, Executive Vice President, BioPharmaceuticals R&D,
said: "This second Phase III trial of baxdrostat shows substantial
improvement in blood pressure, which reflects its durable half-life
of up to 30 hours and highly selective inhibition of aldosterone
synthase. Too many patients today have hypertension that remains
hard-to-control throughout the day and night, making them
especially vulnerable to cardiac events. We are advancing our
regulatory filings and rapidly progressing our robust clinical
development programme for baxdrostat, as both a mono- and
combination-therapy, across additional conditions where aldosterone
plays a key role, including primary aldosteronism, chronic kidney
disease and heart failure prevention."
The data will be shared with regulatory authorities around the
world and presented in a late-breaking session at the American
Heart Association (AHA) Scientific Sessions in November
2025.
Baxdrostat is designed to lower blood pressure by specifically
inhibiting aldosterone, a key hormone that raises blood pressure
and increases the risk of heart and kidney problems. Phase I
studies show baxdrostat reached peak levels in the blood within 2
to 4 hours and had a half-life of about 26 to 30
hours.11,12 Baxdrostat
is currently being investigated as a monotherapy for
hypertension13-15 and
primary aldosteronism,16 and
in combination with dapagliflozin for chronic kidney
disease17,18 and
the prevention of heart failure in high-risk
patients.19
Notes
Hard-to-control hypertension
Hypertension is a medical condition characterised by consistently
high blood pressure levels, affecting an estimated 1.4 billion
people worldwide.4,20,21 Over
time, this can damage blood vessels and vital organs, increasing
the risk of serious health problems such as heart attack, stroke,
heart failure and kidney disease.20,21 An
observational study of nearly 60,000 patients studied over a median
of 9.7 years showed that a 9.5 mmHg increase in SBP was associated
with a 30% increase in risk of all-cause mortality and 41% increase
in risk of cardiovascular death.10Studies
have shown that increased night-time blood pressure is associated
with higher cardiovascular risk,7,10 and
patients with hypertension have a higher risk of cardiovascular
events like heart attack, stroke and death around the time of their
morning blood pressure surge.1,2
Hard-to-control (uncontrolled and resistant) hypertension remains a
major public health challenge.22 Despite
lifestyle changes and the use of multiple medications,
approximately 50% of patients in the US who are being treated for
hypertension still do not have their blood pressure under
control.5 Uncontrolled
hypertension refers to persistently elevated blood pressure despite
the use of two or more medications, while rHTN, a more severe form,
remains elevated despite treatment with three or more
medications.5,20
A key contributor to hard-to-control hypertension is aldosterone, a
hormone that raises blood pressure by promoting sodium and water
retention.23,24 Elevated
aldosterone levels, along with factors such as obesity, high salt
intake, and various genetic or secondary
conditions,25 are
strongly associated with poor blood pressure control. When left
untreated, hypertension significantly increases the risk of
cardiovascular and kidney-related complications.20,21
Bax24 trial
The Phase III Bax24 trial15 is
a randomised, double-blind, placebo-controlled, parallel group
study to evaluate the safety, tolerability and the effect of 2mg
baxdrostat versus placebo, administered once a day (QD) orally, on
the reduction of ambulatory SBP in participants with rHTN. A total
of 218 patients were randomised in a 1:1 ratio to receive
baxdrostat 2mg or placebo once daily during a 12-week double blind
period. The primary efficacy endpoint was the change from baseline
in ambulatory 24-hour average SBP at Week 12.
Additional secondary endpoints include the effect of baxdrostat
versus placebo on change from baseline in ambulatory night-time
average SBP at Week 12, change from baseline in ambulatory daytime
average SBP at Week 12, change from baseline in seated SBP at Week
12, the number of participants achieving ambulatory 24-hour average
SBP of less than 130 mmHg at Week 12 and the number of participants
achieving a nocturnal SBP dipping of greater than 10% at Week 12.
Occurrence of adverse events was evaluated during the 12-week
treatment period as well as during a 2-week safety follow-up
period.
Baxdrostat
Baxdrostat is a potential first-in-class, highly selective and
potent, oral, small molecule that inhibits aldosterone
synthase,11 an
enzyme encoded by the CYP11B2 gene, which is responsible for the
synthesis of aldosterone in the adrenal gland.23 In
clinical trials, baxdrostat was observed to significantly lower
aldosterone levels without affecting cortisol levels across a wide
range of doses.12,26 Baxdrostat
is currently being investigated in clinical trials as a monotherapy
for hypertension13-15 and
primary aldosteronism,16 and
in combination with dapagliflozin for chronic kidney disease and
hypertension,17,18 and
the prevention of heart failure in patients with
hypertension.19
AstraZeneca acquired baxdrostat through its purchase of CinCor
Pharma, Inc. in February 2023.27
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'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. Renna NF, et al. Morning blood
pressure surge as a predictor of cardiovascular events in patients
with hypertension. Blood Press
Monit. 2023;28(3):149-157
2. Kario K et al. Morning
hypertension: the strongest independent risk factor for stroke in
elderly hypertensive patients. Hypertens
Res. 2006;29(8):581-7.
3. Staplin N, et al. Relationship
between clinic and ambulatory blood pressure and mortality: an
observational cohort study in 59 124
patients. Lancet.
2023;401(10393):2041-2050.
4. Flack JM, et al. Efficacy and
Safety of Baxdrostat in Uncontrolled and Resistant
Hypertension. N
Engl J Med. 2025. Aug
30:10.1056/NEJMoa2507109. doi:
10.1056/NEJMoa2507109.
5.
World Health Organization. Global report on hypertension 2025: high
stakes: turning evidence into action. 2025.
https://iris.who.int/handle/10665/382841. Accessed September
2025.
6. Carey RM, et al. Prevalence of
Apparent Treatment-Resistant Hypertension in the United
States. Hypertension. 2019;73(2):424-431.
Accessed September 2025.
7. Narita K, et al. Nighttime Home
Blood Pressure Is Associated With the Cardiovascular Disease Events
Risk in Treatment-Resistant Hypertension. Hypertension.
2022;79(2):e18-e20
8. Kario K, et al. Nighttime Blood
Pressure Phenotype and Cardiovascular
Prognosis. Circulation. 2020;142(19):1810-1820
9. Williams B, et al. 2018 ESC/ESH
Guidelines for the management of arterial hypertension: The Task
Force for the management of arterial hypertension of the European
Society of Cardiology (ESC) and the European Society of
Hypertension (ESH). European Heart
Journal.
2018;39(33):3021-3104.
10. Niiranen TJ, Mäki J, Puukka
P, Karanko H, Jula AM. Office, home, and ambulatory
blood pressures as predictors of cardiovascular risk. Hypertension.
2014 Aug;64(2):281-6. doi: 10.1161/HYPERTENSIONAHA.114.03292. PMID:
24842916. Accessed September 2025.
11. Bogman K, et al. Preclinical and early
clinical profile of a highly selective and potent oral inhibitor of
aldosterone synthase (CYP11B2). Hypertension. 2017;69(1):189-196.
Accessed September 2025.
12. Freeman MW, et al. Results from a phase
1, randomized, double-blind, multiple ascending dose study
characterizing the pharmacokinetics and demonstrating the safety
and selectivity of the aldosterone synthase inhibitor baxdrostat in
healthy volunteers. Hypertens
Res. 2023;46(1):108-118.
Accessed September 2025.
13.
ClinicalTrials.gov.A Study to Investigate the Efficacy and Safety
of Baxdrostat in Participants With Uncontrolled Hypertension on Two
or More Medications Including Participants With Resistant
Hypertension (BaxHTN). Available at:
https://clinicaltrials.gov/study/NCT06034743. Accessed September
2025.
14.
ClinicalTrials.gov. A Study to Investigate the Efficacy and Safety
of Baxdrostat in Participants With Uncontrolled Hypertension on Two
or More Medications Including Participants With Resistant
Hypertension (BaxAsia). Available at:
https://clinicaltrials.gov/study/NCT06344104. Accessed September
2025.
15.
ClinicalTrials.gov. A Study to Investigate the Effect of Baxdrostat
on Ambulatory Blood Pressure in Participants With Resistant
Hypertension (Bax24). Available at:
https://clinicaltrials.gov/study/NCT06168409. Accessed
September 2025.
16.
ClinicalTrials.gov. A Study to Assess Efficacy and Safety of
Baxdrostat in Participants With Primary Aldosteronism (BaxPA).
Available at: https://clinicaltrials.gov/study/NCT07007793.
Accessed September 2025.
17.
ClinicalTrials.gov. A Phase III Study to Investigate the Efficacy
and Safety of Baxdrostat in Combination With Dapagliflozin on CKD
Progression in Participants With CKD and High Blood Pressure.
Available at: https://clinicaltrials.gov/study/NCT06268873.
Accessed September 2025.
18.
ClinicalTrials.gov. A Phase III Renal Outcomes and Cardiovascular
Mortality Study to Investigate the Efficacy and Safety of
Baxdrostat in Combination With Dapagliflozin in Participants With
Chronic Kidney Disease and High Blood Pressure (BaxDuo-Pacific).
Available at: https://clinicaltrials.gov/study/NCT06677060.
Accessed September 2025.
19.
ClinicalTrials.gov. Phase III Study Investigating Heart Failure and
Cardiovascular Death With Baxdrostat in Combination With
Dapagliflozin (Prevent-HF). Available at:
https://clinicaltrials.gov/study/NCT06677060. Accessed
September 2025.
20. McEvoy JW, et al. 2024 ESC Guidelines
for the management of elevated blood pressure and
hypertension. Eur Heart
J. 2024;45(38):3912-4018.
Accessed September 2025.
21. Whelton PK, et al. 2017
ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the
prevention, detection, evaluation, and management of high blood
pressure in adults: Executive summary: A report of the American
College of Cardiology/American Heart Association task force on
clinical practice guidelines. Hypertension. 2018;71(6):1269-1324.
Accessed September 2025.
22. NCD Risk Factor Collaboration
(NCD-RisC). Worldwide trends in hypertension prevalence and
progress in treatment and control from 1990 to 2019: a pooled
analysis of 1201 population-representative studies with 104 million
participants. Lancet. 2021 Sep 11;398(10304):957-980. doi:
10.1016/S0140-6736(21)01330-1.
23. Cannavo A, et al. Aldosterone and
mineralocorticoid receptor system in cardiovascular physiology and
pathophysiology. Oxid Med Cell
Longev. 2018;2018:1204598.
Accessed September 2025.
24. Inoue K, et al. Serum aldosterone
concentration, blood pressure, and coronary artery calcium: The
multi-ethnic study of atherosclerosis. Hypertension. 2020;76(1):113-120.
Accessed September 2025.
25. van Oort S, et al. Association of
cardiovascular risk factors and lifestyle behaviors with
hypertension: a mendelian randomization study. Hypertension. 2020;76(6):1971-1979.
26. Freeman MW, et al. Phase 2 trial of
baxdrostat for treatment-resistant hypertension. N Engl J
Med. 2023;388(5):395-405.
Accessed September 2025.
27.
AstraZeneca 2023. Acquisition of CinCor Pharma complete.
https://www.astrazeneca.com/media-centre/press-releases/2023/astrazeneca-acquires-cincor-for-cardiorenal-asset.html.
Accessed September 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.
|
|
AstraZeneca
PLC
|
Date: 07 October 2025
|
|
By: /s/
Matthew Bowden
|
|
|
Name:
Matthew Bowden
|
|
|
Title:
Company Secretary
|