The US Food and Drug Administration (FDA) recently approved AstraZeneca's hypoglycemic drug Farxiga (Chinese trade name: Andatang, generic name: dapagliflozin, dapagliflozin) for a new indication for ejection fraction Reduced heart failure (HFrEF) in adult patients (with or without type 2 diabetes) to reduce the risk of cardiovascular (CV) death and hospitalization of heart failure. The indication was approved through the FDA ’s priority review process.
Farxiga is the first selective sodium glucose co-transporter 2 (SGLT2) inhibitor administered orally once daily. It is worth mentioning that Farxiga is the first SGLT2 inhibitor approved for the treatment of heart failure, specifically: New York Heart Association (NYHA) functional class II-IV heart failure adult patients with reduced ejection fraction . Data from the milestone phase III DAPA-HF trial showed that in adult patients with HFrEF (with or without type 2 diabetes), when combined with standard care, Farxiga improved survival rates and reduced The need to significantly reduce the risk of CV death and heart failure exacerbation (heart failure hospitalization, emergency heart failure visits) composite endpoint by 26%.
In September 2019, the FDA granted Farxiga Fast Track Qualification (FTD) for adult patients with heart failure (HFpEF) with HFrEF or ejection fraction retention, reducing the risk of cardiovascular death (CV) death or worsening heart failure. In August 2019, FD also awarded Farxiga another FTD for chronic kidney disease (CKD) patients with or without type 2 diabetes, delaying the progression of renal failure and preventing CV and kidney death.
In the United States, Farxiga was previously approved as a monotherapy and as part of a combination therapy for adults with type 2 diabetes to improve blood sugar control. In October 2019, the FDA also approved Farxiga for patients with type 2 diabetes, cardiovascular disease, or multiple CV risk factors to reduce the risk of heart failure hospitalization.
Norman Stockbridge, MD, director of the Department of Cardiology and Nephrology of the FDA Center for Drug Evaluation and Research, said: "Heart failure is a serious health condition that causes the death of one in eight Americans and affects nearly 6.5 million Americans. The latest approval will provide an additional treatment option for patients with heart failure (HFrEF) with reduced ejection fraction, which can improve survival and reduce the need for hospitalization. "
This approval is based on the results of the milestone phase III DAPA-HF test. The results of this study were published in the New England Journal of Medicine (NEJM) in September 2019. Results showed that in patients with heart failure (HFrEF) with reduced ejection fraction (with or without type 2 diabetes), when combined with standard care, Farxiga reduced the incidence of CV death or HF worsening composite outcomes compared to placebo .
DAPA-HF is an evaluation of an SGLT2 inhibitor combined with standard care drugs (including angiotensin converting enzyme [ACE] inhibitors, angiotensin II receptor blockers [ARB], beta-blockers, mineralocorticoid Hormone receptor antagonist [MRA] and enkephalinase inhibitors) the first heart failure outcome study in adults with HFrEF (with and without type 2 diabetes). This is an international, multicenter, parallel group, randomized, double-blind study conducted in patients with heart failure (HFrEF) with reduced ejection fraction (LVEF≤40%), including with and without type 2 diabetes Of patients. The study evaluated the efficacy and safety of Farxiga combined with standard place-of-care treatment at a daily dose of 10 mg. The primary endpoint of the study was the time of worsening heart failure events (hospitalization or equivalent events, such as emergency heart failure visits) or cardiovascular (CV) death.
The results showed that the study reached the primary composite endpoint: compared to placebo, Farxiga significantly reduced the risk of cardiovascular (CV) death or worsening of the composite endpoint of heart failure by 26% (p <0.0001), and showed that each composite endpoint The risk of each individual component has been reduced. The specific data are: the risk of the first deterioration of heart failure is reduced by 30% (p <0.0001), and the risk of cardiovascular death is reduced by 18% (p = 0.0294). Farxiga's effect on the primary composite endpoint was roughly the same in the key subgroups studied. In addition, the results also showed that patients reported by the Kansas City Cardiomyopathy Questionnaire (KCCQ) reported a significant improvement, with a nominally significant reduction in all-cause mortality by 17% (7.9 vs 9.5 patients per 100 patient years). Good for Farxiga. In this study, the safety of Farxiga is consistent with the established safety of the drug. The proportion of patients with insufficient capacity (7.5% vs 6.8%) and renal adverse events (6.5% vs 7.2%) is comparable to placebo, which is an event that is often concerned when treating heart failure. Major hypoglycemia events (0.2% vs 0.2%) in both treatment groups were rare.
Heart failure (HF) is a life-threatening disease in which the heart cannot pump enough blood into the body. Heart failure affects approximately 64 million people worldwide (at least half of whom have decreased ejection fractions). This is a chronic, degenerative disease, and half of the patients will die within 5 years of diagnosis. Heart failure remains as deadly as the most common cancers in men (prostate cancer and bladder cancer) and women (breast cancer). Heart failure is the main reason for hospitalization of patients over 65 years of age and represents a significant clinical and economic burden.
The active pharmaceutical ingredient of Farxiga is dapagliflozin (daggliflozin), which is a pioneer, once-daily oral, selective sodium-glucose co-transporter (SGLT2) inhibitor that has been approved for type 2 diabetes Adult patients improve blood sugar control. The drug works independently of insulin and selectively inhibits SGLT2 in the kidney, which can help patients excrete excess glucose from urine. In addition to lowering blood sugar, the drug has the additional benefits of losing weight and lowering blood pressure.
AstraZeneca is advancing a huge clinical development project of dapagliflozin, involving more than 35 completed or ongoing Phase IIb / III clinical studies, enrolling more than 35,000 patients, and having more than 2.5 million patient years of clinical experience.
It is worth mentioning that in March 2019, Forxiga (the European trade name of dapagliflozin) was approved by the European Union and Japan for a new indication: as an oral adjuvant therapy for insulin, for the treatment of adult patients with type 1 diabetes (T1D). The drug is the first SGLT2 inhibitor approved for the treatment of T1D in Europe and the first T1D drug with regulatory approval from AstraZeneca. The specific indications for this medicine are: As an oral adjuvant therapy for insulin, it is used for adult patients receiving insulin therapy but with poorly controlled blood glucose levels and body mass index (BMI) ≥27kg / m2 (overweight or obese) type 1 diabetes (T1D) To improve its blood sugar control. However, in the United States, the drug was rejected by the FDA in July 2019 for the treatment of T1D due to the risk of diabetic ketoacidosis (DKA).
In China, dapagliflozin (Chinese brand name: Anda Tang) was approved in March 2017 as a monotherapy for improving blood glucose control in adults with type 2 diabetes. This approval makes dapagliflozin the first SGLT2 inhibitor approved in the Chinese market. This medicine is an oral tablet, each tablet contains 5mg or 10mg dapagliflozin, the recommended starting dose is 5mg each time, taken once a day in the morning.