Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
sacubitril/valsartan · 5 trials · 4 indications
Number of participants with treatment emergent adverse events (any AE regardless of seriousness), and SAEs.
To demonstrate the effect of sacubitril/valsartan vs. valsartan on time-averaged proportional change in N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to weeks 4 and 8 in heart failure with preserved ejection fraction (HFpEF) patients with a worsening heart failure event (HFpEF decompensation) who have been stabilized for and initiated at the time of or within 30 days post-decompensation. Plasma NT-proBNP (pg/mL) values were averaged from Week 4 and Week 8 visits. The change from baseline to average of Week 4 and Week 8 was expressed as the geometric mean of the ratio: Week - 8/Baseline. NT-proBNP is a protein produced in large amounts by the heart when it is not working properly, as in heart failure. Baseline value was the last non-missing assessment of plasma NT-proBNP before the first administration of study drug.
Number of participants with at least one Adverse Events (AEs)
Number of participants with at least one Serious Adverse Events (SAEs)
Median duration of exposure to sacubitril/valsartan (including temporary interruptions)
To demonstrate that LCZ696 is superior to individualized medical therapy for comorbidities in reducing NT-proBNP from baseline at Week 12 in patients with HFpEF
Change from baseline in 6-minute walk distance (6MWD) will be reported at Week 24. The 6 MWT will be performed in accordance with the guidelines of the American Thoracic Society 2002.
Cardiovascular magnetic resonance imaging (MRI) scans were obtained at baseline prior to randomization, at week 52 for the assessment of local aortic distensibility. Ascending aorta distensibility was one of the 3 components for measuring local arota distensibility.
Cardiovascular magnetic resonance imaging (MRI) scans were obtained at baseline prior to randomization, at week 52 for the assessment of local aortic distensibility. Proximal descending aorta distensibility was one of the 3 components for measuring local arota distensibility.
Cardiovascular magnetic resonance imaging (MRI) scans were obtained at baseline prior to randomization, at week 52 for the assessment of local aortic distensibility. Distal descending aorta distensibility was one of the 3 components for measuring local arota distensibility.
| Arm | Type | Description |
|---|---|---|
| sacubitril/valsartan | EXPERIMENTAL | The starting dose of study drug was determined by the investigator in consideration of the participant´s condition. The dose level at the end of study visit of CLCZ696B2319E1 study could remain the same, or the dose level could be changed at the discretion of the investigator. |
| sacubitril/valsartan (LCZ696) | EXPERIMENTAL | Study treatment was titrated to the target dose of sacubitril/valsartan (LCZ696) 97/103 mg twice daily (Dose Level 3). Patients were required to take a total of two tablets twice daily (one tablet of active sacubitril and valsartan , and one tablet of valsartan matching placebo) |
| valsartan | ACTIVE_COMPARATOR | Study treatment was titrated to the target dose of valsartan 160 mg twice daily (Dose Level 3). Patients were required to take a total of two tablets twice daily (one tablet of active valsartan, and one tablet of sacubitril and valsartan matching placebo) |
| Comparator | ACTIVE_COMPARATOR | Patients randomized to the comparator arm will receive either enalapril (ACE stratum) valsartan (ARB stratum) or LCZ696 matching placebo (no RASi stratum). Patients in the ACE stratum randomized to comparator, will receive enalapril in titrated doses from level 1 up to level 3 (2.5 mg, 5 mg and 10 mg twice daily). Patients in the ARB stratum randomized to comparator will receive valsartan in titrated doses from level 1 up to level 3 (40 mg , 80 mg and 160 mg twice daily). Patients in the no RASi stratum randomized to comparator will receive LCZ696 matching placebo. |
| olmesartan | ACTIVE_COMPARATOR | Single drug treatment period: Patients received 20 mg olmesartan q.d + placebo to LCZ696 200mg once daily (q.d.) for 2 weeks. After 2 weeks, patients were dosed at the maintenance dose level (40 mg olmesartan q.d + placebo to 400 mg qd LCZ696) for 10 weeks. Add-on Period: After 12 weeks on single-drug treatment, patients continued in the study on the blinded maintenance dose and if required, open label amlodipine (2.5 mg, 5 mg, or 10 mg qd) was added to the treatment regimen and titrated according to the investigator's discretion to achieve target blood pressure. |
| Name | Type | Description |
|---|---|---|
| sacubitril/valsartan | DRUG | sacubiril/valsartan |
| valsartan | DRUG | Valsartan was available as 40 mg, 80 mg, and 160 mg in tablet form to be taken orally, twice daily |
| sacubitril/valsartan matching placebo | DRUG | Sacubitril/valsartan (LCZ696) matching placebo was available as tablet form to be taken orally, twice daily |
| valsartan matching placebo | DRUG | Valsartan matching placebo was available as tablet form to be taken orally, twice daily |
| Enalapril | DRUG | Enalapril is available as 2.5 mg, 5 mg, and 10 mg tablet form to be taken orally |
| Placebo to match sacubitril/valsartan | DRUG | Placebo to match LCZ696 50 mg, 100 mg, 200 mg tablet form to be taken orally |
| Placebo to match enalapril | DRUG | Placebo to match enalapril 2.5 mg, 5 mg, 10 mg tablet form to be taken orally |
| Placebo to match valsartan | DRUG | Placebo to match valsartan 40 mg, 80 mg, 160 mg tablet form to be taken orally |
| sacubitril/valsartan (LCZ696) | DRUG | 200 mg tablets |
| olmesartan | DRUG | - |
| placebo to sacubitril/valsartan (LCZ696) | OTHER | placebo |
| placebo to olmesartan | OTHER | placebo |
| Amlodipine (Optional) | DRUG | If required, open label amlodipine (2.5 mg, 5 mg, or 10 mg qd) was added to treatment regimen |
Inclusion Criteria: * Signed informed consent * \<18 years of age (at the time of signing informed consent) * Completed CLCZ696B2319E1 study and safely enrolled Exclusion Criteria: * Permanently discontinued the study treatment during CLCZ696B2319E1 study * Renal vascular hypertension (including ...
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Sacubitril/valsartan is used for heart failure, heart failure with preserved ejection fraction (HFpEF), and hypertension. It is a small molecule cardiovascular drug being developed by Novartis AG (NVS).
Sacubitril/valsartan is a combination of a neprilysin inhibitor and an angiotensin receptor blocker. It works by inhibiting neprilysin and blocking the angiotensin II receptor, which helps manage heart failure and hypertension.
Sacubitril/valsartan is developed by Novartis AG, a pharmaceutical company listed on the stock exchange under the ticker NVS.
Sacubitril/valsartan is in Phase 3 clinical development. It is an investigational drug and has not been approved by regulatory authorities. Clinical trials are completed, including studies in heart failure and hypertension.
Sacubitril/valsartan has completed clinical trials including NCT01870739 for hypertension, NCT03066804 for heart failure with preserved ejection fraction, and NCT03785405 for heart failure in pediatric patients. These trials are completed.
Yes, sacubitril/valsartan is also known as LCZ696. Clinical trials such as NCT01870739 and NCT03066804 refer to the drug as LCZ696, which is the same compound as sacubitril/valsartan.