AstraZeneca’s Farxiga (Dapagliflozin) Approved in India as the First SGLT2 Inhibitor for Heart Failure Treatment

July 06, 2020 News /Bio ValleyBIOON/ --AstraZeneca(AstraZeneca) recently announced that its drug Forxiga (Chinese brand name: Andatang; generic name: dapagliflozin) has been approved in India for a new indication: the treatment of adult patients with heart failure with reduced ejection fraction (HFrEF).

Forxiga is a once-daily oral selective sodium-glucose cotransporter 2 (SGLT2) inhibitor. In early May this year, Farxiga (dapagliflozin) received the first global approval in the United States for the treatment of adult patients with heart failure with reduced ejection fraction (HFrEF). Additionally, the Canadian Cardiovascular Society (CCS) has updated its guidelines to recommend the use of SGLT2 inhibitors (such as dapagliflozin) for the treatment of heart failure to provide better patient care.

It is worth noting that Forxiga/Farxiga is the first SGLT2 inhibitor approved for the treatment of HFrEF, and the first proven to significantly reduce risks in patients with HFrEF (with or without type 2Diabetes) medications that reduce 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 2DiabetesGlycemic control in patients; (2) for type 2 diabetes with established cardiovascular disease or multiple cardiovascular risk factorsDiabetespatients, reducing the risk of hospitalization for heart failure. In the European Union and Japan, this drug is also approved for the treatment of type 1 diabetes, specifically as an oral adjunct to insulin therapy to improve glycemic control in adult patients with type 1 diabetes (T1D) who are receiving insulin but have inadequate glycemic control and have a body mass index (BMI) ≥27 kg/m² (overweight or obese).

This latest approval is based on data from the landmark Phase III DAPA-HF trial. The results showed that in adult patients with HFrEF (with or without type 2Diabetes) When combined with standard of care, Forxiga/Farxiga improved survival and reduced the need for hospitalization compared with placebo, significantly reducing by 26% the risk of the composite endpoint of cardiovascular death and worsening heart failure (hospitalization for heart failure, urgent visits for 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, added 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 showed 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), and demonstrated risk reductions in each individual component of the composite endpoint, specifically: a 30% reduction in the risk of first worsening of heart failure (p<0.0001) and an 18% reduction in the risk of cardiovascular death (p=0.0294). The effect of Farxiga on the primary composite endpoint was generally consistent across key subgroups studied. Furthermore, the results showed significant improvement 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 with volume depletion (7.5% vs. 6.8%) and renal adverse events (6.5% vs. 7.2%) were comparable to those with placebo, which 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 the leading cause of hospitalization among patients aged 65 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 that acts independently of insulin. It selectively inhibits SGLT2 in the kidneys, helping patients excrete excess glucose through urine. In addition to lowering blood glucose levels, this medication 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 involving more than 35 completed or ongoing Phase IIb/III clinical studies, with over 35,000 enrolled patients and more than 2.5 million patient-years of clinical use experience.

Original Source:AstraZeneca’s Dapagliflozin (Forxiga) approved in India for treatment of patients with Heart Failure with reduced ejection fraction