New analyses from Phase III PARAGON-HF trial demonstrate potential clinical impact for certain patients with heart failure with preserved ejection fraction (HFpEF)1-4
New data from PROVE-HF and EVALUATE-HF studies provide insight on Entresto’s mechanism of action in patients with heart failure with reduced ejection fraction (HFrEF)5,6
New PIONEER-HF findings provide additional data on in-hospital initiation of Entresto for HFrEF patients following initial stabilization7,8
Breadth of data demonstrate longstanding commitment to improving heart failure care and reinforce Entresto as a first-choice therapy for HFrEF1-13
EAST HANOVER, N.J., November 12, 2019 — Novartis will present analyses for Entresto® (sacubitril/valsartan) across the continuum of care – inpatient and outpatient – in chronic heart failure at the upcoming American Heart Association’s (AHA) Scientific Sessions 2019, taking place November 16–18 in Philadelphia. These data further build on the breadth of data supporting the use of Entresto as a first-choice treatment to help improve clinical outcomes.1-13
Important results will be shared via two late-breaking trial presentations, one oral/rapid fire presentation and nine posters. Data includes new analyses of:1-10
Entresto in HFpEF (PARAGON-HF)
Entresto on reverse cardiac remodeling (PROVE-HF and EVALUATE-HF)
In-hospital use of Entresto (PIONEER-HF)
Registry data on quality of life and clinical outcomes for comorbid HFrEF and diabetes, and on improvement in left ventricular ejection fraction in HFrEF outpatients (CHAMP-HF)
"These new analyses add to an unprecedented body of evidence that has established Entresto as a guideline-recommended and first-choice therapy for patients with HFrEF and suggest potential for addressing needs in HFpEF,” said David Soergel, M.D., Global Head of Cardiovascular, Renal and Metabolic Drug Development at Novartis. “Since its approval nearly five years ago, Entresto has played a significant role in reducing the burden of HFrEF. These new analyses provide valuable information about the use of Entresto across the continuum of heart failure care, both in and out of the hospital. These insights support us in our efforts to reimagine outcomes for patients with heart failure.”
Highlights of Entresto data at the AHA Scientific Sessions 2019 include:
Two late-breaking new analyses of PARAGON-HF, which is the largest Phase III HFpEF clinical trial conducted to date.3,4,14The randomized, double-blind, Phase III event-driven study evaluated the long-term efficacy and safety profile of Entresto against an active comparator (valsartan) in HFpEF, a disease with high unmet need and no currently approved treatment.14-16 The composite primary endpoint of reducing cardiovascular death and total heart failure hospitalizations narrowly missed statistical significance but showed evidence of treatment effect against an active comparator and was presented at ESC 2019.17 New analyses provide data about safety and efficacy of Entresto in women with HFpEF, in HFpEF patients who were previously hospitalized and, via a pooled analysis with PARADIGM-HF, among patients in different LVEF categories.1,3,4 Quality of life data from PARAGON-HF will also be presented.2
New data from the PROVE-HF and EVALUATE-HF trials in HFrEF providing additional insight into the effect of Entresto’s unique mechanism of action.5,6,18,19 Previously reported data from PROVE-HF showedEntresto improved measures of heart structure and function, indicative of reversal of cardiac remodeling, and data from EVALUATE-HF complemented these findings.18,19 Cardiac remodeling refers to changes that occur in the heart as a result of disease or after injury and leads to poor prognosis due to its negative effects on heart function.20,21 The ability to reverse cardiac remodeling may restore function and improve clinical outcomes.20,21
About our longstanding commitment to heart failure
Sacubitril/valsartan (approved as Entresto® since 2015) is a first-choice treatment in heart failure with reduced ejection fraction (HFrEF), based on its superiority to the angiotensin-converting enzyme (ACE) inhibitor enalapril in its ability to significantly reduce CV death and HFrEF hospitalizations.11-13,22 Entresto plays a critical role in keeping people with HFrEF out of the hospital and helps reduce the staggering economic burden of the disease, which has been estimated to exceed $30 billion annually in the U.S. (accounting for both direct and indirect costs).23
Novartis undertook the largest global clinical program in the heart failure disease area across the pharmaceutical industry to date, called FortiHFy. The program comprises over 40 active, completed or planned clinical studies designed to generate an array of additional data on symptom reduction, efficacy, quality of life benefits and real-world evidence with Entresto, as well as to extend understanding of heart failure.
Through the Entresto scientific program, Novartis is reimagining the standard of care for HFrEF patients and the use of Entresto as a first-choice therapy in HFrEF as well as its potential in heart failure with preserved ejection fraction (HFpEF), a condition for which there is currently no approved treatment.11-13,14-16 Beyond PARAGON-HF, additional studies investigating Entresto on other relevant endpoints in HFpEF are ongoing.
About Entresto for heart failure with reduced ejection fraction
Entresto (sacubitril/valsartan) is a prescription medicine used to reduce the risk of cardiovascular death and heart failure hospitalization in people with long-lasting (chronic) heart failure (HFrEF).22 Entresto is usually used with other heart failure therapies, in place of an angiotensin-converting enzyme (ACE) inhibitor or other angiotensin II receptor blocker (ARB) therapy.22 Entresto is a twice-a-day prescription medicine that works by enhancing the beneficial neurohormonal systems (natriuretic peptide system) while simultaneously inhibiting the harmful effects of the overactive renin-angiotensin-aldosterone system (RAAS).22,24 Most other heart failure medicines only block the harmful effects of the overactive RAAS. Entresto contains the neprilysin inhibitor sacubitril and the ARB valsartan.22 Entresto film-coated tablets are available in three dosage strengths: 24/26 mg, 49/51 mg and 97/103 mg (sacubitril/valsartan).22 These doses are referred to as 50 mg, 100 mg and 200 mg in the clinical trial literature including The New England Journal of Medicine publication of the results of PARADIGM-HF.11 In adult patients, the target maintenance dose of Entresto is 97/103 mg twice daily as tolerated by the patient.22
IMPORTANT SAFETY INFORMATION
Entresto can harm or cause death to an unborn baby. Patients should talk to their doctor about other ways to treat heart failure if they plan to become pregnant. If a patient gets pregnant while taking Entresto, she should tell her doctor right away.
Patients are not to take Entresto if they are allergic to sacubitril or valsartan or any of the ingredients in Entresto; have had an allergic reaction including swelling of the face, lips, tongue, throat or trouble breathing while taking a type of medicine called an ACE inhibitor or ARB; or take an ACE inhibitor medicine. Patients are not to take Entresto for at least 36 hours before or after they take an ACE inhibitor medicine. Patients should talk with their doctor or pharmacist before taking Entresto if they are not sure if they take an ACE inhibitor medicine. Patients are not to take Entresto if they have diabetes and take a medicine that contains aliskiren.
Before they take Entresto, patients should tell their doctor about all of their medical conditions, including if they have kidney or liver problems; or a history of hereditary angioedema; are pregnant or plan to become pregnant; are breastfeeding or plan to breastfeed. Patients should either take Entresto or breastfeed. They should not do both.
Patients should tell their doctor about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. They should especially tell their doctor if they take potassium supplements or a salt substitute; nonsteroidal anti-inflammatory drugs (NSAIDs); lithium; or other medicines for high blood pressure or heart problems such as an ACE inhibitor, ARB, or aliskiren.
Entresto may cause serious side effects including serious allergic reactions causing swelling of the face, lips, tongue, and throat (angioedema) that may cause trouble breathing and death. Patients are to get emergency medical help right away if they have symptoms of angioedema or trouble breathing. Patients are not to take Entresto again if they have had angioedema while taking Entresto. People who are black or who have had angioedema may have a higher risk of having angioedema if they take Entresto. Entresto may cause low blood pressure (hypotension). Patients are to call their doctor if they become dizzy or lightheaded, or they develop extreme fatigue. Entresto may cause kidney problems or an increased amount of potassium in the blood.
The most common side effects in adults were low blood pressure, high potassium, cough, dizziness, and kidney problems.
Patients are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
Novartis is committed to providing patients with affordable access and resources through Entresto Central. For more information, please call 1-888-ENTRESTO or visit www.entresto.com.
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “expect,” “anticipate,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political and economic conditions; safety, quality or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
Novartis is reimagining medicine to improve and extend people’s lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. Novartis products reach more than 750 million people globally and we are finding innovative ways to expand access to our latest treatments. About 108 000 people of more than 140 nationalities work at Novartis around the world. Find out more at www.novartis.com.
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Vaduganathan M, Claggett B, Anker S, et al. Prior Heart Failure Hospitalization, Clinical Outcomes, and Effect of Sacubitril/Valsartan Compared With Valsartan in Heart Failure With Preserved Ejection Fraction. Data presented at: AHA Scientific Sessions 2019, Nov 16-18; Philadelphia, USA.
Lewis E, Linssen G, Tuvia B, et al. Impact of Sacubitril/Valsartan on Health-Related Quality of Life in Heart Failure-Preserved Ejection Fraction Patients. Data presented at: AHA Scientific Sessions 2019, Nov 16-18; Philadelphia, USA.
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