AstraZeneca’s Forxiga (dapagliflozin) Label Updated in EU with DECLARE-TIMI 58 Data Demonstrating Significant Reduction in Heart Failure Hospitalizations and Cardiovascular Death in Type 2 Diabetes Patients

August 06, 2019 /BioValleyBIOON/ -- British pharmaceutical giantAstraZeneca(AstraZeneca) recently announced that the European Commission (EC) has approved the SGLT2 inhibitor antidiabetic drug Forxiga (Chinese brand name: Andatang; generic name: dapagliflozin) for the treatment of type 2Diabetesto amend the European marketing authorization for patients with type 2 diabetes (T2D) to include outcome data from the landmark cardiovascular outcomes trial (CVOT) DECLARE-TIMI 58. Regulatory applications to incorporate these clinical data into the Forxiga product label are currently under review by regulatory authorities in the United States and China.

Mene Pangalos, Executive Vice President of BioPharmaceuticals R&D at AstraZeneca, stated: “For type 2DiabetesFor patients, heart failure occurs after a heart attack orStrokeone of the earliest cardiovascular complications. In the Phase III DECLARE-TIMI 58 study, Forxiga reduced type 2DiabetesComposite endpoint of hospitalization for heart failure or cardiovascular death. We look forward to in the EU for type 2Diabetespatients derive these additional benefits.”

DECLARE-TIMI 58 is the largest and most extensive cardiovascular outcomes trial (CVOT) conducted to date for SGLT2 inhibitors. This randomized, double-blind, placebo-controlled, multicenter study, sponsored by AstraZeneca, evaluated the impact of Forxiga versus placebo on cardiovascular (CV) outcomes in adult patients with type 2 diabetes (T2D) at risk of CV events, including those with multiple CV risk factors and those with established CV disease. The study involved more than 17,000 patients across 33 countries.

The results showed that, compared with placebo, Forxiga significantly reduced the composite risk of heart failure hospitalization (hHF) or cardiovascular (CV) death by 17% (4.9% vs. 5.8%; HR=0.83 [95% CI: 0.73–0.95]; p=0.005), meeting one of the two primary efficacy endpoints of the study. The reduction in hHF or CV risk was consistent across the entire study population, including patients with CV risk factors and those with established CV disease.

Regarding other primary efficacy endpoints, Forxiga was associated with fewer major adverse cardiovascular events (MACE) compared with placebo, although the difference did not reach statistical significance (Forxiga 8.8% vs. placebo 9.4%; HR=0.93 [95% CI: 0.84–1.03]; p=0.17). Furthermore, for the composite renal endpoint, Forxiga reduced the incidence of new or worsening nephropathy by 24% compared with placebo in the broad study population (4.2% vs. 5.6%; HR=0.76 [95% CI: 0.67–0.87]) and was associated with lower all-cause mortality (6.2% vs. 6.6%; HR=0.93 [95% CI: 0.82–1.04]).

The study also confirmed the established safety profile of Forxiga, demonstrating non-inferiority in the primary safety endpoint by showing no increased risk of major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction, and stroke) compared with placebo. Furthermore, there were no imbalances between Forxiga and placebo in other safety assessments, including amputation (1.4% vs. 1.3%), fracture (5.3% vs. 5.1%), bladder cancer (0.3% vs. 0.5%), and Fournier’s gangrene (1 case vs. 5 cases). The incidences of diabetic ketoacidosis (0.3% vs. 0.1%) and genital infections (0.9% vs. 1.0%) were both rare.

There are 425 million people with diabetes worldwide, among whom patients with type 2 diabetes have a 2- to 5-fold higher risk of heart failure, myocardial infarction andStrokeIncreased risk. The 5-year survival rate after a heart failure diagnosis is only 50%. New findings from the DECLARE-TIMI 58 study will better address this serious and often overlooked cardiovascular complication.

The active pharmaceutical ingredient of Forxiga is dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor approved to improve glycemic control in adult patients with type 2 diabetes. The drug 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.

In March this year, Forxiga received further approval in the EU and Japan for a new indication: as an oral adjunct to insulin for the treatment of adult patients with type 1 diabetes (T1D). It is the first SGLT2 inhibitor approved in Europe for the treatment of T1D and the first T1D drug to receive regulatory approval for AstraZeneca. The specific indication is as an oral adjunct to insulin to improve glycemic control in adult patients with type 1 diabetes (T1D) who are on insulin therapy but have inadequate glycemic control and have a body mass index (BMI) ≥27 kg/m² (overweight or obese).

Currently, AstraZeneca is advancing an extensive clinical development program for dapagliflozin, encompassing more than 35 Phase IIb/III clinical studies that have been completed or are ongoing, with over 35,000 patients enrolled.

In China, dapagliflozin (brand name: Forxiga) 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. (Bioon.com)

Original Source:AstraZeneca Website