AstraZeneca's Dapagliflozin Nears Approval in China for HFrEF Indication

On February 1, the official website of the National Medical Products Administration (NMPA) indicated that the marketing applications for two new受理号 (JXHS2000027 and JXHS2000028) of AstraZeneca's dapagliflozin had entered the "under review" stage. The impending approval is for a new indication of dapagliflozin: for the treatment of adult patients with heart failure with reduced ejection fraction (HFrEF), to reduce the risk of cardiovascular death and worsening heart failure, and to improve heart failure symptoms.

AstraZeneca submitted the application for marketing approval of this new indication to the NMPA on March 17 last year. The application was publicly disclosed on May 13 and formally included in the priority review by the CDE on May 26.

Dapagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that received FDA approval in January 2014. It currently has three approved indications in the United States: 1) type 2 diabetes mellitus; 2) reduction of the risk of hospitalization for heart failure in patients with type 2 diabetes or those at risk of cardiovascular death; and 3) reduction of the risk of cardiovascular death or worsening heart failure in patients with heart failure with reduced ejection fraction (HFrEF). On January 6 this year, the FDA granted priority review to the supplemental new drug application for dapagliflozin for the treatment of adults with newly diagnosed or worsening chronic kidney disease (CKD). (Recommended reading: AstraZeneca’s Dapagliflozin Receives FDA Priority Review for Chronic Kidney Disease Indication.)

Dapagliflozin was first approved for marketing in China in March 2017 for the treatment of type 2 diabetes, under the brand name Forxiga. In November 2019, it was included in the National Reimbursement Drug List (Category B) through medical insurance negotiations. Last December, dapagliflozin was renewed into the 2020 National Reimbursement Drug List at prices of RMB 2.56 per tablet (5 mg) and RMB 4.36 per tablet (10 mg).

The results of the international, multicenter, phase III DAPA-HF clinical trial involving 4,744 patients demonstrated that adding dapagliflozin to standard heart failure therapy reduced the relative risk of the primary composite endpoint by 26%. Specifically, the risk of cardiovascular death was significantly reduced by 18%, and the risk of worsening heart failure was significantly reduced by 30%.

Furthermore, the DAPA-HF trial demonstrated that dapagliflozin was equally effective in patients with and without type 2 diabetes, indicating that the reduction in heart failure hospitalization risk by SGLT2 inhibitors is independent of glycemic status.

The latest data from subgroup analyses also demonstrate that dapagliflozin reduces the incidence of the primary composite endpoint in patients with heart failure with reduced ejection fraction (HFrEF) receiving extensive pharmacological therapy, device-based therapy, and cardiac resynchronization therapy.

Heart failure (HF) affects approximately 64 million people worldwide and is the leading cause of hospitalization among individuals aged 65 years and older. It is estimated that half of patients with heart failure die within five years of diagnosis, a mortality rate comparable to that of the most common cancers in men (prostate and bladder cancer) and women (breast cancer).