REG - AstraZeneca PLC - Farxiga reduced risk of CV death or worsening HF

AstraZenecaAnnouncement

30/08/2022 07:16

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RNS Number : 4512X  AstraZeneca PLC  30 August 2022

30 August 2022 07:00 BST

 

Farxiga significantly reduced the risk of cardiovascular death or worsening of
heart failure in patients with mildly reduced or preserved ejection fraction
in DELIVER Phase III trial

 

Results presented at European Society of Cardiology Congress 2022, and
published in New England Journal of Medicine

 

Data extend the clinically meaningful benefits of Farxiga in patients with
heart failure regardless of ejection fraction

 

Heart failure is a chronic, progressive disease impacting nearly 64 million
people

 

Detailed results from the DELIVER Phase III trial showed AstraZeneca's Farxiga
(dapagliflozin) significantly reduced the composite of cardiovascular (CV)
death or worsening heart failure (HF) in patients with HF and mildly reduced
or preserved ejection fraction (EF), compared to placebo. The results were
presented today at the European Society of Cardiology Congress 2022 in
Barcelona, Spain, and simultaneously published in The New England Journal of
Medicine(1).

 

Farxiga reduced the composite outcome of CV death or worsening of HF by 18%
(p<0.001, 16.4% in the dapagliflozin group and 19.5% in the placebo group
over a median follow-up of 2.3 years). All individual components contributed
to the superiority of the primary endpoint. The findings were consistent
across key subgroups examined and extend the benefits of Farxiga to the full
spectrum of patients with HF irrespective of left ventricular ejection
fraction (LVEF) status. The trial results also showed a symptom benefit in
patient-reported outcomes measured by the Kansas City Cardiomyopathy
Questionnaire (KCCQ) total symptom score(1).

 

Dr. Scott Solomon, Professor of Medicine at Harvard Medical School and Brigham
and Women's Hospital and Principal Investigator of the DELIVER Phase III
trial, said: "These results from DELIVER are important for patients and
clinical care as it shows that dapagliflozin is effective regardless of
ejection fraction and therefore can be used as foundational therapy in all
eligible patients with heart failure. Earlier HFpEF trials have shown
attenuation in the highest LVEF but with dapagliflozin results are consistent
across the LVEF range. The findings also reinforce most recent treatment
guidelines, recommending earlier initiation of guideline-directed medical
treatment and may support broader use of SGLT2 inhibitors in clinical
practice."

 

The updated 2022 joint HF guidelines issued by the American College of
Cardiology, the American Heart Association and the Heart Failure Society of
America, now recommend sodium-glucose cotransporter 2 (SGLT2) inhibitors such
as Farxiga for HF with mildly reduced EF (HFmrEF) and HF with preserved EF
(HFpEF). This expands upon previous recommendations supporting the use of
SGLT2 inhibitors in HF with reduced EF (HFrEF)(2).

 

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D,
AstraZeneca, said:

"Heart failure patients with LVEF greater than 40% are the most difficult to
treat with few treatment options available to them. We are proud to share the
groundbreaking DELIVER results, which have expanded our understanding of the
complexities of HF. These data build upon our previous studies demonstrating
cardiorenal protection of Farxiga across patients with type-2 diabetes,
chronic kidney disease and heart failure."

 

DELIVER was designed with broader inclusion criteria than prior trials in this
patient population to also include patients who were hospitalised, recently
hospitalised, or those with HF with improved LVEF, for whom evidence-based
therapy is limited(1,2). These findings build upon the previously reported
results from DAPA-HF, the only SGLT2 inhibitor outcomes trial in HF to
demonstrate a significant reduction in mortality, to provide further evidence
to support the use of Farxiga as foundational therapy for patients with HF,
regardless of ejection fraction.

 

The safety and tolerability profile of Farxiga in the DELIVER Phase III trial
was consistent with the well-established safety profile of the medicine.

 

Notes

 

HF

HF is a chronic, long-term condition that worsens over time(3). It affects
nearly 64 million people globally and is associated with substantial morbidity
and mortality(4,5). Chronic HF is the leading cause of hospitalisation for
those over the age of 65 and represents a significant clinical and economic
burden(6). There are several types of HF often defined by LVEF, a measurement
of the percentage of blood leaving the heart each time it contracts,
including: HFrEF (LVEF less than or equal to 40%), HFmrEF (LVEF 41-49%) and
HFpEF (LVEF greater than or equal to 50%)(2). Approximately half of all HF
patients have HFmrEF or HFpEF, with few therapeutic options available(2,7).

 

DELIVER

DELIVER was an international, randomised, double-blind, parallel-group,
placebo-controlled, event-driven Phase III trial designed to evaluate the
efficacy of Farxiga, compared with placebo, in the treatment of HF patients
with LVEF greater than 40%, with or without T2D. Farxiga was given once daily
in addition to background therapy (regional standard of care  SoC  for all
comorbidities, including diabetes and hypertension, with the exception of
concomitant use of a SGLT2 inhibitor)(8).DELIVER is the largest clinical trial
to date in HF patients with LVEF above 40%, with 6,263 randomised
patients(8,9).

 

The primary endpoint was the time to first occurrence of CV death,
hospitalisation for HF (hHF) or an urgent HF visit. The secondary endpoint
includes the total number of HF events (hHF or urgent HF visit) and CV death,
change from baseline in the total symptom score of the KCCQ at eight months,
time to the occurrence of CV death and time to the occurrence of death from
any cause(8).

 

Farxiga

Farxiga (dapagliflozin) is a first-in-class, oral, once-daily SGLT2 inhibitor.
Research has shown Farxiga's efficacy in preventing and delaying cardiorenal
disease, while also protecting the organs - important findings given the
underlying links between the heart, kidneys and pancreas(10-12). Damage to one
of these organs can cause the other organs to fail, contributing to leading
causes of death worldwide, including type-2 diabetes (T2D), HF and chronic
kidney disease (CKD)(4,13-15).

 

Farxiga is approved for adults and children aged 10 years and above for the
treatment of insufficiently controlled T2D mellitus as an adjunct to diet and
exercise. Farxiga is also approved for the treatment of HFrEF and the
treatment of CKD based on the findings of the DAPA-HF and DAPA-CKD Phase III
trials.

 

DapaCare is a robust programme of clinical trials to evaluate the potential
CV, renal and organ protection benefits of Farxiga. It includes more than 35
completed and ongoing Phase IIb/III trials in more than 35,000 patients, as
well as more than 2.5 million patient-years' experience. Farxiga is currently
being tested in patients without T2D following an acute myocardial infarction
or heart attack in the DAPA-MI Phase III trial - a first of its kind,
indication-seeking registry-based randomised controlled trial.

 

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 and pancreas, AstraZeneca is investing in a
portfolio of medicines for organ protection and improving outcomes by slowing
disease progression, reducing risks and tackling co-morbidities. The Company's
ambition is to modify or halt the natural course of CVRM diseases and
potentially regenerate organs and restore function, by continuing to deliver
transformative science that improves treatment practices and CV health for
millions of patients worldwide.

 

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 (https://www.astrazeneca.com/) and follow the
Company on Twitter @AstraZeneca (https://twitter.com/AstraZeneca) .

 

Contacts

For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
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.

 

References

1.   Solomon S, et al. Dapagliflozin in Heart Failure with Mildly Reduced or
Preserved Ejection Fraction. N Engl J Med 2022 [cited 2022 Aug 27] Available
from: www.nejm.org/doi/full/10.1056/NEJMoa2206286
(https://protect-de.mimecast.com/s/4CL8Cmq1nkC1l3RP9sOaZIr?domain=nejm.org)

2.   Heidenreich PA, 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):e263-421.

3.   Cleveland Clinic  Internet . Heart failure; [cited 2022 Jul 26]
Available
from: https://my.clevelandclinic.org/health/diseases/17069-heart-failure-understanding-heart-failure
(https://my.clevelandclinic.org/health/diseases/17069-heart-failure-understanding-heart-failure)

4.   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. Lancet 2017; 390(10100):1211-59.

5.   Mozaffarian D, et al. Heart disease and stroke statistics-2016
update. Circulation. 2016; 133(4):e38-360.

6.   Azad N, et al. Management of chronic heart failure in the older
population. J Geriatr Cardiol. 2014; 11(4):329-37.

7.   Dunlay SM, et al. Epidemiology of heart failure with preserved ejection
fraction. Nat Rev Cardiol 2017;14(10):591-602.

8.   Solomon SD, et al. Dapagliflozin in heart failure with preserved and
mildly reduced ejection fraction: rationale and design of the DELIVER
trial. Eur J Heart Fail 2021; 23(7):1217-25.

9.   Clinicaltrials.gov  Internet . Dapagliflozin Evaluation to Improve the
LIVEs of Patients With Preserved Ejection Fraction Heart Failure; [cited 2022
Jul 26]. Available from: https://clinicaltrials.gov/ct2/show/NCT03619213
(https://clinicaltrials.gov/ct2/show/NCT03619213) .

10.  McMurray JJV, et al. Dapagliflozin in patients with heart failure and
reduced ejection fraction. N Engl J Med 2019; 381(21):1995-2008.

11.  Heerspink HJL, et al. Dapagliflozin in patients with chronic kidney
disease. N Engl J Med 2020; 383(15):1436-46.

12.  Wiviott SD, et al. for the DECLARE-TIMI 58 Investigators. Dapagliflozin
and cardiovascular outcomes in type-2 diabetes [article and supplementary
appendix]. N Engl J Med 2019; 380(4):347-57.

13.  Mayo Clinic  Internet . Heart failure, 2020; [cited 2022 Jul 26].
Available
from: https://www.mayoclinic.org/diseases-conditions/heart-failure/symptoms-causes/syc-20373142
(https://www.mayoclinic.org/diseases-conditions/heart-failure/symptoms-causes/syc-20373142)
.

14.  Centers for Disease Control and Prevention (CDC)  Internet . A snapshot:
Diabetes in the United States, 2020; [cited 2022 Jul 26]. Available
from: https://www.cdc.gov/diabetes/library/socialmedia/infographics/diabetes.html
(https://www.cdc.gov/diabetes/library/socialmedia/infographics/diabetes.html)
.

15.  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
 Internet . Heart disease & kidney disease, 2016; [cited 2022 Jul 26].
Available
from: https://www.niddk.nih.gov/health-information/kidney-disease/heart-disease
(https://www.niddk.nih.gov/health-information/kidney-disease/heart-disease) .

 

 

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

 

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