AstraZeneca's Forxiga Receives Japanese Approval for Chronic Kidney Disease Treatment

Compiled by | Fan Dongdong

Recently, AstraZeneca announced that Japan's Ministry of Health, Labour and Welfare (MHLW) has approved Forxiga (dapagliflozin) for the treatment of adult patients with chronic kidney disease (CKD) with or without type 2 diabetes (T2D). Earlier this year, the drug was granted priority review designation by the MHLW.

AstraZeneca noted that Forxiga is the first drug approved in Japan for the treatment of this disease. In early August, Forxiga was also approved by the European Commission (EC) for the treatment of adult patients with new-onset or worsening chronic kidney disease (CKD), with or without type 2 diabetes (T2D), making it the first SGLT2 inhibitor approved in the EU for the treatment of CKD.

Chronic kidney disease (CKD) is a serious, progressive condition characterized by a gradual decline in renal function, which may also increase the risk of heart disease or stroke. Notably, the diagnosis rate for chronic kidney disease remains low, with up to 90% of patients unaware that they have the condition. The active pharmaceutical ingredient in Forxiga is dapagliflozin. This medication primarily works by inhibiting SGLT2 expressed in the kidneys, thereby reducing renal glucose reabsorption and increasing urinary glucose excretion to lower blood glucose levels. Furthermore, its glucose-lowering efficacy is independent of β-cell function and insulin resistance.

The drug's approval in Japan was primarily based on the positive results of the Phase III DAPA-CKD trial. This multicenter, randomized, double-blind, late-stage trial enrolled 4,304 patients with CKD stages 2 to 4 across 386 centers in 21 countries. The trial aimed to evaluate the effect of Forxiga 10 mg versus placebo, each in combination with standard of care, on renal outcomes and cardiovascular death in patients with chronic kidney disease (with or without type 2 diabetes).

Trial results showed that, on top of standard therapy with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, Forxiga further reduced the relative risk of worsening renal function or onset of end-stage renal disease. Compared with placebo, in patients with CKD stages 2 to 4 and elevated urinary albumin excretion, treatment with Forxiga reduced the risk of cardiovascular or renal death by 39%, with an absolute risk reduction of 5.3%.

Furthermore, the trial met all secondary endpoints. Compared with placebo, Forxiga significantly reduced the relative risk of all-cause mortality by 31%. In the trial, the safety and tolerability profile of Forxiga was consistent with its previously established safety profile. Fewer serious adverse events occurred in the Forxiga group compared with the placebo group (29.5% vs. 33.9%, respectively). Based on these positive results, Forxiga is the first medication to significantly prolong survival in a renal outcomes trial of CKD patients with and without type 2 diabetes.

In 2013, AstraZeneca KK, the Japanese subsidiary of AstraZeneca, entered into a collaboration agreement with Ono Pharmaceutical regarding Forxiga. Under the agreement, Ono Pharmaceutical will be responsible for the distribution and marketing of Forxiga in Japan. Previously, the drug had also been approved in Japan for the treatment of type 1 diabetes (T1D). Data from the Phase III DEPICT clinical program conducted in Japanese patients showed that at Week 24, compared with placebo, both doses of Forxiga (5 mg and 10 mg) produced statistically and clinically significant improvements in patients' glycated hemoglobin (HbA1c), body weight, and total daily insulin dose.

Marketed under the brand name Farxiga in the United States, the drug was approved by the U.S. Food and Drug Administration (FDA) in May 2020 as an oral tablet for the treatment of adult patients with heart failure with reduced ejection fraction (HFrEF), to help reduce the risk of cardiovascular death and hospitalization for heart failure. In 2017, the drug (dapagliflozin) was approved in China for improving and controlling blood glucose in adult patients with type 2 diabetes, becoming the first SGLT2 inhibitor antidiabetic drug marketed in China.

References:

1.AstraZeneca's Forxiga Approved In Japan For Chronic Kidney Disease - Quick Facts

2.Forxiga Approved in Japan