Delving into the Latest Updates on Sacubitril/Valsartan with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

AHU-377/valsartan, Enrest, LCZ

+ [17]

Target

AT1R x CD10

Action

antagonists, inhibitors

Mechanism

AT1R antagonists(Angiotensin II Receptor Type 1 antagonists), enkephalinase inhibitors(Neprilysin inhibitors)

Therapeutic Areas

Cardiovascular DiseasesUrogenital Diseases

Active Indication

Essential HypertensionHypertensionLeft ventricular systolic dysfunction+ [5]

Inactive Indication

Acute myocardial infarctionAortic DiseasesErectile Dysfunction+ [10]

Originator Organization

Novartis Pharma AG

Active Organization

Novartis Pharmaceuticals Corp.

Novartis AGNovartis Europharm Ltd.

+ [5]

Inactive Organization

Novartis Pharma AG

Beijing Novartis Pharma Co. Ltd.Novartis Pharma Stein AG

License Organization

Novartis Pharma KK

Otsuka Pharmaceutical Co., Ltd.

Drug Highest PhaseApproved

First Approval Date

United States (07 Jul 2015),

Chronic heart failure

RegulationFast Track (United States), Priority Review (China)

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Structure/Sequence

Molecular FormulaC48H61N6NaO9

InChIKeyBHNNEXLQFVQGSE-LWRBNZNASA-N

CAS Registry936623-90-4

Angiotensin-neprilysin inhibitors (ARNI) are beneficial in patients with heart failure with reduced ejection fraction. No study evaluating ARNI has been conducted in sub-Saharan Africa (except South Africa) yet, where heart failure is a major health problem. Before implementing ARNI in Tanzania, a study evaluating the benefit and safety of ARNI in Africans is needed. The aim of this interventional pre-post study is to evaluate the health status of symptomatic patients with heart failure with reduced ejection fraction who are under a chronic heart failure therapy, before and after switching angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) to ARNI. Participants will be recruited at the Heart and Lung Clinic of the St Francis Regional Referral Hospital in Ifakara in rural Tanzania during a study period of 30 months, including 10 months of follow-up. A total of 238 participants will be included. The investigators hypothesize that health status, expressed by the Kansas City Cardiomyopathy Questionnaire summary score and 6-minute walking test, will improve after switching from ACE-inhibitors or ARB to ARNI. In Tanzania, sacubitril/valsartan is registered under the name Uperio®.

Start Date01 Aug 2025

Sponsor / Collaborator

Swiss Tropical & Public Health Institute

[+1]

NCT07017751

/ Not yet recruitingNot ApplicableIIT

The Effect of Education on Symptom Burden, Medication Adherence, Nutritional Behaviour in Patients With Heart Failure

This study aims to determine the effect of online education structured according to Pender's Health Promotion Model on symptom burden, medication adherence, and nutritional behaviour in patients with heart failure. The sample size was calculated using the 'G. Power-3.1.9.2' programme at a 95% confidence level prior to data collection. Accordingly, the minimum sample size required for the independent sample t-test for the study was determined to be 44 (22 for each group) based on an alpha value of 0.05, an effect size of 1.128, and a theoretical power of 95%. Taking data losses into account, a total of 60 patients (30 for each group) were planned to be included in the sample. Data will be collected using the Heart Failure Symptom Status Scale, Medication Adherence and Prescription Printing Scale (İURYÖ-7), Heart Failure Nutrition Behaviour Scale. 1: Prior to providing education to patients, they will be informed about the purpose of the study, the data collection method, and the topics to be covered in the education. Patients who agree to participate in the study will be asked to sign an informed consent form. All patients in the experimental and control groups will be asked to complete the Heart Failure Nutrition Behaviour Scale (HFNBS), Heart Failure Symptom Status Scale (HFSSS), and Medication Adherence and Prescription Writing Scale (MAPWS-79) before receiving education.
2: The contact information of all patients in the experimental group will be collected. Training will be provided online at a time and date convenient for the patients.
3: Patients in the control group will receive a digital training booklet prepared by the researcher at the contact address they provide.
4: Participants will be contacted 2 weeks, 1 month, and 2 months after the initial education session to obtain feedback on post-education dietary behaviours, medication adherence, and symptoms.
5: Four to six weeks after the training is completed, the 'Nutritional Behaviour Scale in Heart Failure,' 'Heart Failure Symptom Status Scale,' and 'Medication Adherence and Prescription Writing Scale (İURYÖ-7)' will be completed online again. The same forms will also be completed online by patients in the control group 4-6 weeks later.

Start Date15 Jul 2025

Sponsor / Collaborator

Canakkale Onsekiz Mart University

NCT06536309

/ Not yet recruitingPhase 4IIT

Neprilysin Inhibition to Reduce Myocardial Fibrosis in Heart Failure With Preserved Ejection Fraction

Cardiac magnetic resonance imaging (MRI) measures of myocardial interstitial fibrosis (MIF) are elevated in heart failure with preserved ejection fraction (HFpEF) patients and associated with poor prognosis. Extracellular volume (ECV) is the most reproducible and best validated cardiac MRI measure of MIF. Sacubitril/valsartan reduces histological MIF in mice and levels of some extracellular matrix regulatory proteins in humans with HFpEF. However, the effect of sacubitril/valsartan on robust measures of MIF in humans is unknown. Demonstrating reductions in ECV with sacubitril/valsartan would clarify the mechanism of this approved medication. Given the borderline reduction in heart failure hospitalizations with sacubitril/valsartan and the heterogeneity of HFpEF pathophysiology, this result would suggest that neprilysin inhibition may particularly benefit HFpEF patients with greater MIF. The investigators propose a proof-of-concept clinical trial to evaluate the effect of neprilysin inhibition (sacubitril/valsartan vs valsartan alone) on cardiac MRI measures of fibrosis (principally ECV) and circulating protein levels.

Start Date01 Jul 2025

Sponsor / Collaborator

The Brigham & Women's Hospital, Inc.

100 Clinical Results associated with Sacubitril/Valsartan

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100 Translational Medicine associated with Sacubitril/Valsartan

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100 Patents (Medical) associated with Sacubitril/Valsartan

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675

Literatures (Medical) associated with Sacubitril/Valsartan

01 Sep 2025·HEART & LUNG

Clinical outcomes of sacubitril-valsartan versus angiotensin converting enzyme inhibitor or angiotensin receptor blocker among patients with heart failure and ejection fraction at/less than 60 %: A retrospective, observational, parallel cohort, multi-group study

Article

Author: Albert, Nancy M ; Bena, James F ; Martyn, Trejeeve ; Khairnar, Rahul ; Faulkenberg, Kathleen ; Williams, J Bradley ; Morrison, Shannon L

BACKGROUND:

Real-world heart failure (HF) and all-cause hospitalization, HF-related emergency care visits, all-cause mortality and the composite of all-cause or HF hospitalization or HF-related emergency visit remain high, due to underuse of core HF medications.

OBJECTIVES:

A better understanding of real-world clinical outcomes is needed based on sacubitril-valsartan vs. angiotensin converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) use among patients with HF and a wide range of ejection fractions.

METHODS:

Data retrieved from a multi-center, multi-state healthcare system database of patients prescribed sacubitril-valsartan were matched to those on ACEI/ARB based on age, sex, EF, comorbidity status, systolic blood pressure and index date site (hospital or ambulatory). Six- and 12-month outcomes based on sacubitril-valsartan vs. ACEI/ARB were assessed using linear, logistic, and Poisson models with generalized estimating equations.

RESULTS:

Patients (N = 4188; 2094/cohort) were well matched based on characteristics; 29.8 % were female, mean (SD) age was 64.3 (13.1) years, systolic blood pressure was 122.0 (16.2) mmHg, EF% was 29.1 (9.9); nearly half were in NYHA FC II and 422 (10.1 %) had EF of 41-60 %. Frequency of non-study medications at baseline was 92.6 % beta-blocker, 43.2 % mineralocorticoid receptor antagonist and 64.2 % loop diuretic. Compared to ACEI/ARB, all 6 and 12-month clinical outcomes were improved among patients using sacubitril-valsartan (all 12-month p<.001).

CONCLUSIONS:

Among patients with HF and EF up to 60 %, sacubitril-valsartan use was associated with lower 12-month morbidity and mortality. Providers and clinicians need to advocate for use of sacubitril-valsartan per hierarchical renin angiotensin system inhibitor national guideline recommendations.

01 Aug 2025·INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

Neprilysin, a novel recombinant venom protein from Habrobracon hebetor, influenced host immunity in vitro

Article

Author: Fang, Qi ; Ye, Gongyin ; Zhong, Haiying ; Zhang, Juefeng ; Zhang, Bo ; Yu, Kaili ; Li, Fang ; Xu, Hongxing ; Song, Qisheng

Ectoparasitoid wasps inject venom into their hosts during the parasitism to paralyze the hosts and inhibit their immune response and development. The venom of the parasitoid wasp, Habrobracon hebetor, contains proteins that facilitate its parasitization of various lepidopteran pests, and paralyze the 3rd to 5th instar larvae of Spodoptera litura. We comparatively analyzed the function of venom protein neprilysin (NEP) from H. hebetor in two different hosts. NEP is a highly conserved endopeptidase present in various insect tissues. H. hebetor contains 17 NEPs, but only one venom-specific NEP was identified. The venom HhNEP is composed of 771 amino acids encoded by a 2316 base open reading frame, with a molecular mass of 87.77 kDa containing a conserved M13 peptidase activity domain. It exhibits high total mRNA expression levels in the venom glands. The recombinant HhNEP, expressed in prokaryotic system, could simultaneously inhibit the prophenoloxidase (PPO) activation in the hemolymph and the encapsulation responses in the hemocytes of S. litura and Plodia interpunctella larvae in vitro. Additionally, recombinant HhNEP inhibited the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in hemocytes from two hosts. In conclusion, the venom HhNEP could inhibit the immune response of hosts.

01 Aug 2025·JACC-Heart Failure

Obesity and Risk of Kidney Outcomes in Heart Failure With Preserved Ejection Fraction

Article

Author: Beldhuis, Iris E ; Jhund, Pardeep S ; Desai, Akshay S ; Vaduganathan, Muthiah ; Lassen, Mats C H ; Pitt, Bertram ; Solomon, Scott D ; Ostrominski, John W ; Zannad, Faiez ; Claggett, Brian L ; Zile, Michael R ; Pfeffer, Marc A ; Anand, Inder S ; Butt, Jawad ; Neuen, Brendon L ; Mc Causland, Finnian ; McMurray, John J V ; Biering-Sørensen, Tor ; Lewis, Eldrin F

BACKGROUND:

Obesity is prevalent among patients with heart failure with preserved ejection fraction (HFpEF).

OBJECTIVES:

This study aims to evaluate whether anthropometrics including body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) are associated with kidney outcomes in patients with HFpEF.

METHODS:

In this participant-level pooled analysis of DELIVER, PARAGON-HF, TOPCAT Americas, and I-PRESERVE, we evaluated the impact of adiposity-related anthropometrics on risk of kidney outcomes (sustained eGFR reduction of ≥50%, end-stage kidney disease, or kidney-related death). BMI was collected in all trials and WC was collected in PARAGON-HF and TOPCAT. Multivariable Cox models stratified by trial and treatment were used.

RESULTS:

Overall, 16,919 participants were included in the analysis (71.9 ± 8.7 years of age; 50.7% women). Of these, 18% were normal/underweight, 35% had overweight, and 47% had obesity as assessed by BMI. WC data was available in 6,177 (105 cm; Q1-Q3: 95-116 cm), and 95% had an elevated WHtR (≥0.5). During follow-up (2.3 years; Q1-Q3: 0.6-2.9 years), 339 kidney outcome events accrued. In multivariable models, higher BMI was not associated with incident kidney events (HR: 0.99; 95% CI: 0.96-1.02; P = 0.45, per 1 kg/m²). However, higher WHtR and WC were positively and linearly associated with the risk of kidney outcomes (WC per 10 cm: HR: 1.15 [95% CI: 1.01-1.31]; P = 0.03; WHtR per 0.1 unit: HR: 1.32 [95% CI: 1.07-1.62]; P = 0.01).

CONCLUSIONS:

In this participant-level pooled analysis of 4 large-scale HFpEF outcome trials, obesity and excess abdominal adiposity were highly prevalent. WC and WHtR were associated with an increased risk of kidney outcomes, while BMI was not. (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213) (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711) (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]; NCT00094302) (Irbesartan in Heart Failure With Preserved Systolic Function [I-PRESERVE]; NCT00095238).

256

News (Medical) associated with Sacubitril/Valsartan

12 Jul 2025

·pharma.economictimes.indiatimes.com

Novartis loses bid to block US Entresto generic through 2026

Washington: Novartis cannot block drugmaker MSN Pharmaceuticals from launching a generic version of its blockbuster heart-failure drug Entresto before its patent expires late next year, a Delaware federal judge said on Friday. U.S. District Judge Richard Andrews rejected Novartis' argument that MSN's generic would infringe one of its patents and denied its request to block the generic from launching until after the patent expires in November 2026. Novartis told the court in a separate filing on Friday that India-based MSN may receive U.S. Food and Drug Administration approval for the generic as soon as July 16 and launch it soon after. The generic would cut into the U.S. market for Swiss-based Novartis' best-selling drug, which earned more than $7.8 billion in global revenue last year. Novartis stock was down more than 2% on Friday morning. The company said in a statement that it was disappointed and planned to appeal. Spokespeople for MSN did not immediately respond to a request for comment. Novartis had convinced the U.S. Court of Appeals for the Federal Circuit in January to halt MSN's launch of its generic until July in a separate patent case. (Reporting by Blake Brittain in Washington; Editing by David Bario, Chizu Nomiyama and Kevin Liffey)

Patent InfringementPatent Expiration

03 Jul 2025

·endpoints.news

Novartis' Cosentyx fails Phase 3 study for autoimmune disease

Novartis faced a setback in its ambition to expand its blockbuster drug Cosentyx and compete in an autoimmune condition with products from Roche and AbbVie. The company said Thursday that the drug flopped a Phase 3 study in giant cell arteritis, an inflammatory disorder primarily occurring in older adults where blood vessels become inflamed and restrict blood flow. Novartis did not report specific data, but said Cosentyx when combined with a tapering of steroids did not show significant sustained remission after one year compared to placebo. Relative to other inflammatory and immunological conditions, giant cell arteritis is not a particularly large market. The prevalence is estimated to be about 1 in 10,000 adults older than 50. Cosentyx is already approved in seven indications, including big-market conditions like plaque psoriasis and psoriatic arthritis. It was Novartis’ second-highest seller in 2024, pulling in more than $6.1 billion, behind only the heart drug Entresto. But giant cell arteritis is an area in which makers of several other established drugs have attempted to move, with mixed results. Early attempts suggested some pharma companies saw it as a way to expand their products’ reach as bigger indications approached biosimilar competition. Roche’s Actemra was approved for giant cell arteritis in 2017, after the drug’s primary patent expired two years earlier. The first Actemra biosimilar was greenlit in 2023. J&J’s Tremfya failed a Phase 3 study last year, while AbbVie’s Rinvoq nabbed an approval in April. Neither drug is expected to see a biosimilar competitor until well into the 2030s. Cosentyx falls on the earlier end of that spectrum, as the first patents are expected to run out in 2029. Editor’s note: This article has been updated to correct that the first Cosentyx patents will expire in 2029, not 2026.

Phase 3Drug ApprovalPatent Expiration

26 Jun 2025

·www.fiercebiotech.com

Novartis pens ProFound pact, offering up $750M biobucks per cardiovascular target

Novartis will work with ProFound Therapeutics to develop first-in-class medicines across a range of cardiovascular diseases. \n Novartis is penning a four-year pact with ProFound Therapeutics to create new therapeutics for heart disease, with $750 million in biobucks up for grabs per target.The Swiss pharma is doling out $25 million in upfront and near-term milestone payments while tacking on the chance for ProFound to make up to $750 million in milestones per selected target, plus tiered royalties, according to a June 26 release.Novartis will work with the Flagship Pioneering–founded biotech to develop first-in-class medicines across a range of cardiovascular diseases. The companies did not disclose how many possible targets are included in the deal terms.The pair will use ProFound’s protein detection platform to identify and validate new proteins within the expanded human proteome for possible therapeutic development. “We are excited to collaborate with ProFound and combine our respective expertise and capabilities to explore under-researched biology, uncover new mechanisms and translate pioneering science into life-changing treatments,” Fiona Marshall, Ph.D., president of biomedical research at Novartis, said in the release.Novartis houses Entresto, a heart failure medication that is currently subject to a patent case in which Novartis is trying to block the launch of MSN Pharmaceuticals’ proposed generic. The pharma also touts Leqvio for lowering bad cholesterol plus three late-stage pipeline candidates in cardiovascular indications. Meanwhile, ProFound also has a pact with Pfizer via Flagship’s and Pfizer’s billion-dollar, multiprogram collaboration. Last year, the partners picked ProFound from Flagship’s portfolio to work on developing new obesity drugs.

AHA

100 Deals associated with Sacubitril/Valsartan

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	C09DX04	-

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Essential Hypertension	China	Novartis Pharma Schweiz AG	24 May 2021
Hypertension	Japan	Novartis Pharma KK	29 Jun 2020
Left ventricular systolic dysfunction	United States	Novartis Pharmaceuticals Corp.	01 Oct 2019
Reduced ejection fraction co-occurrent and due to chronic heart failure	European Union	Novartis Europharm Ltd.	19 Nov 2015
Reduced ejection fraction co-occurrent and due to chronic heart failure	Iceland	Novartis Europharm Ltd.	19 Nov 2015
Reduced ejection fraction co-occurrent and due to chronic heart failure	Liechtenstein	Novartis Europharm Ltd.	19 Nov 2015
Reduced ejection fraction co-occurrent and due to chronic heart failure	Norway	Novartis Europharm Ltd.	19 Nov 2015
Heart Failure	Switzerland	Novartis AG	17 Sep 2015
Chronic heart failure	United States	Novartis Pharmaceuticals Corp.	07 Jul 2015

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chronic Kidney Diseases	Phase 3	United States	Chong Kun Dang Pharmaceutical Corp.	14 Oct 2024
Postmyocardial infarction syndrome	Phase 3	-	Novartis Pharmaceuticals Corp.	26 May 2021
Erectile Dysfunction	Phase 3	Germany	Novartis Pharmaceuticals Canada, Inc.	16 Apr 2019
Heart Failure, Systolic	Phase 3	Germany	Novartis Pharmaceuticals Canada, Inc.	16 Apr 2019
Acute myocardial infarction	Phase 3	United States	Novartis Pharmaceuticals Corp.	09 Dec 2016
Acute myocardial infarction	Phase 3	China	Novartis Pharmaceuticals Corp.	09 Dec 2016
Acute myocardial infarction	Phase 3	Argentina	Novartis Pharmaceuticals Corp.	09 Dec 2016
Acute myocardial infarction	Phase 3	Australia	Novartis Pharmaceuticals Corp.	09 Dec 2016
Acute myocardial infarction	Phase 3	Austria	Novartis Pharmaceuticals Corp.	09 Dec 2016
Acute myocardial infarction	Phase 3	Belgium	Novartis Pharmaceuticals Corp.	09 Dec 2016

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


PARADIGM-HF and PARAGON-HF (Pubmed \| JACC Heart Fail)	Not Applicable	Heart Failure N-terminal pro-B type natriuretic peptide (NT-proBNP)	-	Sacubitril/Valsartan	feoadhytam(sbbnjqzcvi) = icrgthzuqx nmdsdsltix (pkjxoklnkq, 5.3 - 6.5)	Positive	01 Jun 2025
NCT01035255 (PARADIGM-HF, Pubmed \| J Am Heart Assoc)	Phase 3	Heart failure with normal ejection fraction	8,399	Sacubitril/Valsartan	joxfzpntrr(jyladxmips): P-Value = 0.62 View more	Positive	06 May 2025
				Enalapril
NCT03988634 (PARAGLIDE-HF, Pubmed \| Am Heart J)	Phase 3	Heart failure with normal ejection fraction NT-proBNP \| LVEF	-	Sacubitril/valsartan	ewuzckjhgu(tdqylvczmu): rate ratio = 0.6 (95% CI, 0.37 - 0.99), P-Value = 0.046 View more	Positive	01 Apr 2025
				Valsartan
ISC2025	Not Applicable	Acute Ischemic Stroke \| Hypertension	-	Sacubitril/Valsartan	yvhsdmmolt(zjeyuzrnyy) = No hypotension occurred in either group wjvqokzaaf (wyovcjcwdl ) View more	Positive	30 Jan 2025
				Other antihypertensive agents
NCT01035255 (PARADIGM-HF, Pubmed \| Eur J Heart Fail)	Phase 3	Heart failure with reduced ejection fraction \| Chronic heart failure	8,399	Beta-blocker	mlhtptxgtv(xjpmwwykhr): HR = 0.47 (95% CI, 0.32 - 0.69) View more	Positive	19 Nov 2024
				No Beta-blocker
NCT02678312 (PANORAMA-HF, Pubmed \| Circulation) Manual	Phase 2/3	Heart Failure	375	Sacubitril/Valsartan	jwtyjcscnz(llxiwhpnld): OR = 0.91 (95% CI, 0.72 - 1.14), P-Value = 0.42 View more	Negative	25 Sep 2024
				Enalapril
NCT01920711 (PARAGON-HF, Pubmed \| Eur J Heart Fail)	Phase 3	Heart Failure	4,795	Sacubitril/valsartan	jxtptghfqm(ofdnbnmuih) = qqlfzcxosw jixrnjnsmx (wrlgnrsfyt, 0.0 - 0.2) View more	Positive	01 Sep 2024
				Valsartan	qpnncexnjk(amrabmfisi) = fjjuqnavpl chqtxekhkc (kfjcojzjiv ) View more
ESC2024	Not Applicable	Heart Diseases	-	ARNI Sacubitril/Valsartan	dnfdnorajm(zuysibzczq) = iapogyziir elrcyohskp (drvjhrtmtq, 806 - 4330)	-	31 Aug 2024
ESC2024	Not Applicable	-	24	sacubitril/valsartan (Control)	wwyyznlpqi(dsmcfygmct) = lxcnjdjtou qutbymgvrq (uhspoxoesn )	Negative	31 Aug 2024
				Sacubitril/Valsartan	wwyyznlpqi(dsmcfygmct) = dbcumjnkku qutbymgvrq (uhspoxoesn )
ESC2024	Not Applicable	Heart Failure	-	Sacubitril/Valsartan (Patients aged below 80 years)	bhfbkspljp(yldncefdxt) = eiybdbzbyz zsqslnyche (ywnpdimdrj )	-	31 Aug 2024
				Sacubitril/Valsartan (Patients aged above 80 years)	bhfbkspljp(yldncefdxt) = liudggsioq zsqslnyche (ywnpdimdrj )