AstraZeneca's Forxiga (Dapagliflozin) Approved in the EU as the First SGLT2 Inhibitor for Heart Failure Treatment

November 09, 2020 /BioValleyBIOON/ --AstraZeneca(AstraZeneca) recently announced that the European Commission (EC) has approved a new indication for the SGLT2 inhibitor Forxiga (Andatang, generic name: dapagliflozin), for the treatment of patients with and without type 2DiabetesAdult patients with symptomatic chronic heart failure with reduced ejection fraction (HFrEF) and type 2 diabetes (T2D).

Heart failure (HF) is a life-threatening chronic condition in which the heart fails to pump sufficient blood to the body. It affects 15 million people in the European Union, at least half of whom have reduced ejection fraction.Forxiga is a once-daily oral selective sodium-glucose cotransporter 2 (SGLT2) inhibitor. In early May this year, Farxiga (dapagliflozin) received the world’s first approval in the United States for the treatment of adult patients with heart failure with reduced ejection fraction (HFrEF).

It is worth noting that Forxiga/Farxiga is the first SGLT2 inhibitor approved for the treatment of HFrEF, and the first proven to significantly reduceDiabetes) medications for reducing the risk of cardiovascular (CV) death and hospitalization for heart failure. Previously, the approved indications for this drug included: (1) as an adjunct to diet and exercise to improve type 2Diabetespatient’s glycemic control; (2) for type 2 diabetes patients with cardiovascular disease or multiple cardiovascular risk factorsDiabetespatients, reducing the risk of hospitalization for heart failure. In the European Union and Japan, the drug is also approved for the treatment of type 1 diabetes mellitus (T1D), specifically as an oral adjunct to insulin therapy to improve glycemic control in adult patients with T1D who are on insulin but have inadequate glycemic control and a body mass index (BMI) ≥27 kg/m² (overweight or obesity).

This new indication approval is based on the results of the landmark Phase III DAPA-HF trial. The data showed that in adult patients with HFrEF (with or without type 2 diabetes), when combined with standard care, Forxiga/Farxiga improved survival rates and reduced the need for hospitalization compared to placebo, significantly lowering the risk of the composite endpoint of cardiovascular death and worsening heart failure (hospitalization for heart failure, urgent visits for heart failure) by 26%.

Dr. John McMurray, from the Cardiovascular Research Centre at the Institute of Cardiovascular and Medical Sciences, University of Glasgow, stated: “Today’s approval provides physicians with a novel therapeutic option for patients with heart failure with reduced ejection fraction (HFrEF), which not only alleviates symptoms and reduces hospitalizations but also improves survival rates.”

Mene Pangalos, Executive Vice President of BioPharmaceuticals R&D at AstraZeneca, stated: “With this latest approval of Forxiga, we will be able to redefine the standard of care for millions of heart failure patients in the European Union. By providing a treatment that can significantly reduce cardiovascular death and hospitalizations, we are one step closer to achieving our goal of preventing or treating heart failure.”

DAPA-HF was the first heart failure outcomes study to evaluate an SGLT2 inhibitor in combination with standard-of-care medications (including angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor blockers [ARBs], beta-blockers, mineralocorticoid receptor antagonists [MRAs], and neprilysin inhibitors) for the treatment of adult patients with heart failure with reduced ejection fraction (HFrEF), both with and without type 2 diabetes. This was an international, multicenter, parallel-group, randomized, double-blind study conducted in patients with HFrEF (LVEF ≤40%), including those with and without type 2 diabetes. The study assessed the efficacy and safety of Farxiga 10 mg once daily versus placebo, in addition to standard-of-care therapy. The primary endpoint was time to first occurrence of a worsening heart failure event (hospitalization or an equivalent urgent visit for heart failure) or cardiovascular (CV) death.

The results demonstrated that the study met its primary composite endpoint: compared with placebo, Farxiga significantly reduced the risk of the composite endpoint of cardiovascular (CV) death or worsening heart failure by 26% (p<0.0001), with risk reductions observed for each individual component of the composite endpoint. Specifically, the risk of first worsening heart failure was reduced by 30% (p<0.0001), and the risk of cardiovascular death was reduced by 18% (p=0.0294). The effect of Farxiga on the primary composite endpoint was generally consistent across key subgroups studied. Furthermore, the results showed significant improvements in patient-reported outcomes as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), and a nominally significant 17% reduction in all-cause mortality (7.9 vs. 9.5 patients with an event per 100 patient-years), favoring Farxiga. In this study, the safety profile of Farxiga was consistent with its established safety profile. The proportions of patients experiencing volume depletion (7.5% vs. 6.8%) and renal adverse events (6.5% vs. 7.2%) were comparable to those in the placebo group; these are events of common concern in the treatment of heart failure. Major hypoglycemic events were rare in both treatment groups (0.2% vs. 0.2%).

Heart failure (HF) is a life-threatening condition in which the heart fails to pump sufficient blood to the body. HF affects approximately 64 million people worldwide (at least half of whom have reduced ejection fraction). It is a chronic, progressive disease, with half of patients dying within five years of diagnosis. Heart failure remains associated with men (prostate cancer and bladder cancer) and women (Breast Cancer) is as lethal as the most common cancers. Heart failure is a leading cause of hospitalization among patients aged 65 years and older, representing a significant clinical and economic burden.

The active pharmaceutical ingredient of Forxiga/Farxiga is dapagliflozin, a first-in-class, once-daily oral selective sodium-glucose cotransporter 2 (SGLT2) inhibitor. It acts independently of insulin by selectively inhibiting SGLT2 in the kidneys, thereby helping patients excrete excess glucose through urine. In addition to its glucose-lowering effects, the drug also hasWeight Lossand the additional benefit of lowering blood pressure.

Currently, Forxiga/Farxiga is also being evaluated for the treatment of chronic kidney disease (CKD); the Phase III DAPA-CKD trial was terminated early due to overwhelming efficacy data. Furthermore, the drug is being assessed for the treatment of heart failure (HF) in the DELIVER (HFpEF) and DETERMINE (HFrEF and HFpEF) trials. The drug has an extensive clinical development program, encompassing more than 35 completed or ongoing Phase IIb/III clinical studies, with over 35,000 patients enrolled, and more than 2.5 million patient-years of clinical use experience.

In China, Forxiga (Chinese brand name: Andatang) was approved in March 2017 as a monotherapy to improve glycemic control in adult patients with type 2 diabetes. This approval made dapagliflozin the first SGLT2 inhibitor approved in the Chinese market. The drug is an oral tablet, with each tablet containing 5 mg or 10 mg of dapagliflozin. The recommended starting dose is 5 mg once daily in the morning.

In late October, the label for Forxiga (Chinese brand name: Andatang) was updated to include data from the landmark cardiovascular outcomes trial (CVOT), the Phase III DECLARE-TIMI 58 study. This is the largest and most extensive CVOT conducted to date on SGLT2 inhibitors. The relevant results were published in the New England Journal of Medicine (NEJM) in January 2019. The data showed that Forxiga reduced the composite risk of hospitalization for heart failure (hHF) or cardiovascular (CV) death in patients with type 2 diabetes (T2D). (Bioon.com)

Original Source: Forxigaapproved in the EU for heart failure