AstraZeneca announced Forxiga China approval to lower the risk of cardiovascular death, heart failure hospitalisation, or urgent Heart Failure(HF) visits in persons with symptomatic chronic Heart Failure. Forxiga was previously approved in China for HF patients with decreased ejection fraction (HFrEF), which means that it is now approved to reduce the risk of cardiovascular death and hospitalisation in adult patients with symptomatic chronic HF regardless of ejection fraction profile.
Forxiga’s Approvals
Forxiga is also approved for the treatment of patients with T2D, HFrEF and CKD in more than 100 countries around the world including China, Japan, the US, and the EU.
Basis of Forxiga China Approval:
The National Medical Products Administration (NMPA) of China granted approval based on positive results from the DELIVER Phase III trial. The pooled analysis of the DELIVER and DAPA-HF Phase III trials also established dapagliflozin as the first HF drug to demonstrate a mortality benefit over the entire ejection fraction range.
Positive Data Readout from DELIVER Clinical trial used in Forxiga China Approval:
DELIVER (Dapagliflozin Evaluation to Improve the LIVEs of Patients with Preserved Ejection Fraction Heart Failure) was an international, randomised, double-blind, parallel-group, placebo-controlled, event-driven Phase III trial that compared Forxiga to placebo in the treatment of HF patients with LVEF greater than 40%, with or without type 2 diabetes (T2D).
DELIVER is the largest clinical trial in HF patients with LVEF more than 40% to date, with 6,263 randomised patients.
The DELIVER Phase III trial results showed that Forxiga met its primary endpoint of lowering the composite outcome of cardiovascular (CV) death or worsening HF by 18% (16.4% in the Forxiga group and 19.5% in the placebo group over a median follow-up of 2.3 years [hazard ratio HR =0.82 95% CI 0.73-0.92; p0.001, ARR 3.1%])
Positive Data Readout from DAPA-HF Clinical trial used in Forxiga China Approval:
DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure) was an international, multi-center, parallel-group, randomised, double-blind Phase III trial in 4,744 patients with HFrEF, with and without T2D, to compare the effect of Forxiga 10mg, given once daily in addition to standard of care, to placebo.
The time to the first incidence of a deteriorating HF episode (hospitalisation or similar event, i.e., an urgent HF visit) or cardiovascular (CV) death was the primary composite endpoint. The average length of follow-up was 18.2 months. The total number of hospitalisations for HF (including repeat admissions) and CV fatalities were key secondary endpoint, as was the change in overall symptom score from baseline to 8 months on the Kansas City Cardiomyopathy Questionnaire (KCCQ).
Hear Failure- Disease Burden in China:
Heart Failure (HF) is a long-term, chronic and complex illness that arises when the heart is unable to pump enough blood around the body. It worsens with time.
Left ventricular ejection fraction (LVEF), a measurement of the percentage of blood leaving the heart each time it contracts, is used to classify different forms of HF, including HFrEF (LVEF less than or equal to 40%), HFmrEF (LVEF 41-49%), and HFpEF (LVEF greater than or equal to 50%). Approximately half of all HF patients have HFmrEF or HFpEF, and there are few treatment choices.
Global Burden of Heart Failure:
It affects roughly 64 million individuals worldwide and is linked to significant morbidity and mortality. Chronic heart failure is the main cause of hospitalisation in those over the age of 65, posing a considerable clinical and economic burden.
Heart Failure Burden in China:
In China, around 4.5 million people suffer with HF. Half of all HF patients die within five years of being diagnosed. Patients with an ejection fraction more than 40% are at a higher risk of death and hospitalisation, have a heavier load of symptoms and physical limitations, and have a lower quality of life.
In terms of healthcare expenditures and resource utilisation, the economic burden of HF in China is enormous, and hospitalisation is the largest contribution to the HF treatment burden – the average hospital stay for HF patients is 30 days per year.
