FDA Grants Jardiance® Breakthrough Therapy Designation for Heart Failure with Preserved Ejection Fraction

September 9, 2021 /BioonBIOON/ -- Boehringer Ingelheim andEli Lilly(Eli Lilly) recently jointly announced that the U.S. Food and Drug Administration (FDA) GrantedBreakthrough Therapy Designation (BTD) for SGLT2 Inhibitor Jardiance (Chinese Brand Name: Outangjing, Generic Name: empagliflozin)，For the treatment of adult patients with heart failure with preserved ejection fraction (HFpEF)。BTD is an FDA drug review pathway designed to expedite the development and review of new drugs intended to treat serious or life-threatening diseases, where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy.

Previously, the FDA granted Fast Track Designation (FTD) to the Jardiance development program, EMPEROR, to reduce the risk of cardiovascular death and hospitalization for heart failure. The EMPEROR program includes the EMPEROR-Reduced trial and the EMPEROR-Preserved trial. Specifically, the results of the EMPEROR-Reduced trial constituted the recent...FDAThe basis for the approval of Jardiance for the treatment of heart failure with reduced ejection fraction (HFrEF). Jardiance is not indicated for the treatment of HFpEF.

FDAJardiance was granted Breakthrough Therapy Designation (BTD) based on the results of the landmark Phase 3 EMPEROR-Preserved trial (NCT03057951). The trial evaluated the efficacy and safety of Jardiance in adult patients with HFpEF. A total of 5,988 patients with heart failure were enrolled in the trial, including 4,005 with a left ventricular ejection fraction (LVEF) ≥50% and 1,983 with LVEF <50%. In the trial, patients were randomized to receive either once-daily oral Jardiance 10 mg (n=2,997) or placebo (n=2,991), in addition to guideline-directed heart failure therapy.The results showed that the trial met the composite primary endpoint:In adult patients with HFpEF, compared with placebo, Jardiance reduced the relative risk of cardiovascular death or hospitalization for heart failure by 21%, demonstrating impressive efficacy. This benefit was consistent across ejection fraction orDiabetesIndependent of status.

Among the more than 6 million cases of heart failure in the United States, HFpEF accounts for approximately half. Currently, there are no approved treatments that can significantly improve the prognosis of patients with HFpEF.According to the results of the EMPEROR-Preserved trial,Jardiance is the first therapy to demonstrate statistically significant improvement in heart failure outcomes in adult patients with HFpEF.. Furthermore, combined with the results of the EMPEROR-Reduced trial (NCT03057977),Jardiance is the first and only therapy to significantly improve outcomes in patients across the full spectrum of heart failure, regardless of ejection fraction.。

Analysis of key secondary endpoints from the EMPEROR-Preserved trial demonstrated that, compared with placebo, Jardiance also reduced the relative risk of first and recurrent heart failure hospitalizations by 27% and significantly slowed the decline in renal function. In this trial, the safety profile of Jardiance was consistent with its known safety profile. The complete data have been published in *The New England Journal of Medicine* (NEJM) under the title:Empagliflozin in Heart Failure with a Preserved Ejection Fraction。

Mohamed Eid, Vice President, Clinical Development and Medical Affairs, Cardiometabolic and Respiratory Medicine at Boehringer Ingelheim, said: "This Breakthrough Therapy Designation highlights the potential of Jardiance to help address the urgent need for clinically proven therapies for patients with this highly prevalent, difficult-to-treat disease. Following the recentFDAFollowing the approval of Jardiance for the treatment of heart failure with reduced ejection fraction (HFrEF), this marks another significant milestone, supporting Jardiance's potential as the first therapy clinically proven to improve outcomes across the entire heart failure spectrum.”

Eli LillyJeff Emmick, Vice President of Product Development, stated: "Given the lack of treatment options for this debilitating disease, the benefits demonstrated in the EMPEROR-Preserved trial represent a significant clinical breakthrough. Together with our partner Boehringer Ingelheim, we look forward to collaborating through this accelerated approval pathway withFDAwork closely together to provide Jardiance to adult patients with heart failure with preserved ejection fraction (HFpEF) as soon as possible.”

EMPEROR-Preserved Primary Endpoint and Heart Failure Hospitalization Outcomes (Click the image to view the full-size image)

Boehringer Ingelheim andEli LillyA global regulatory submission for Jardiance for the treatment of HFpEF is planned for 2021. If approved, Jardiance will become the first clinically validated therapy across the entire heart failure spectrum, offering heart failure patients an opportunity to fundamentally transform their future. In the United States, more than 6 million people live with heart failure, approximately half of whom have HFpEF, also known as diastolic heart failure. Given its prevalence, adverse outcomes, and the lack of clinically proven therapies to date, HFpEF has been described as the greatest unmet need in cardiovascular medicine.

Data from the EMPEROR-Preserved trial supplement the results of the prior Phase 3 EMPEROR-Reduced trial, which showed that: (1) in adult patients with heart failure with reduced ejection fraction (HFrEF), when added to standard of care, Jardiance 10 mg significantly reduced the composite relative risk of cardiovascular death or hospitalization for heart failure by 25% compared with placebo, a result observed in patients with and without type 2Diabetes mellituswas consistent across patient subgroups with T2D. (2) Analysis of key secondary endpoints showed that, compared with placebo, Jardiance reduced the relative risk of first and recurrent hospitalizations for heart failure by 30% and significantly slowed the decline in renal function.

In summary, these studies have demonstrated the benefits of Jardiance across the entire heart failure disease spectrum (including HFrEF and HFpEF). Based on the results of the EMPEROR-Reduced trial, Jardiance was approved for a new indication in the European Union in June 2021 and in the United States in August 2021: for the treatment of adult patients with heart failure with reduced ejection fraction (HFrEF, systolic heart failure) to reduce the risk of cardiovascular death and hospitalization for heart failure, regardless of whether they have type 2 diabetes.Diabetes(T2D). Currently, Jardiance's new indication for the treatment of HFrEF is also under review by the National Medical Products Administration (NMPA) of China.

Heart failure (HF) affects over 60 million people worldwide, and a significant unmet medical need remains in its treatment, as approximately half of diagnosed patients are expected to die within five years. HF is the leading cause of hospitalization among individuals aged 65 and older. HF is the most common and severe complication following a heart attack, occurring when the heart is unable to pump sufficient blood to the rest of the body. Patients with HF frequently experience dyspnea and fatigue, which significantly impair quality of life.

Patients with HF often also have renal impairment, which may have a significant negative impact on prognosis. The mortality risk for HF patients increases with each hospitalization. Heart failure with reduced ejection fraction (HFrEF) occurs when the heart muscle cannot contract effectively, resulting in less blood being pumped into the body compared to a normally functioning heart. Heart failure with preserved ejection fraction (HFpEF) occurs when the heart muscle contracts normally but the ventricles do not contain sufficient blood, resulting in less blood entering the heart compared to a normally functioning heart.

Jardiance (Oujingjing, empagliflozin) is an oral, once-daily, highly selective SGLT-2 inhibitor. The emerging class of SGLT-2 inhibitors has been proven to block glucose reabsorption in the kidneys, promoting the excretion of excess glucose from the body, thereby lowering blood glucose levels. Moreover, this glucose-lowering effect is independent of β-cell function and insulin resistance. In addition to its well-established glucose-lowering efficacy, the drug also provides additional benefits, including weight reduction, blood pressure lowering, and uric acid reduction. Jardiance demonstrates a favorable safety profile and can reduceDiabetesReduces the risk of cardiovascular events in patients, and is the world's first type 2 diabetes medication clinically proven to reduce the risk of cardiovascular mortality.

Jardiance was approved for marketing in August 2014 for the treatment of patients with type 2 diabetes. In late 2016, Jardiance received additional approval to reduce the risk of cardiovascular death in patients with type 2 diabetes and established cardiovascular disease. In recent years,Eli Lilly-The Boehringer Ingelheim Alliance has long been committed to developing this drug for the treatment of heart failure and chronic kidney disease. (Bioon.com)

Original Source:FDA grants Jardiance® Breakthrough Therapy designation for heart failure with preserved ejection fraction