Forxiga Approved in Japan for Chronic Heart Failure

AstraZeneca’s Forxiga (dapagliflozin) has been approved in Japan for the treatment of patients with chronic heart failure (HF) who are receiving standard of care.

HF is a life-threatening chronic disease that prevents the heart from pumping sufficient levels of blood around the body. It affects approximately 64 million people worldwide, at least half of whom have a reduced ejection fraction. This occurs when the left ventricle muscle is not able to contract adequately and therefore expels less oxygen-rich blood into the body.

“Heart failure is a condition affecting 1.3 million people in Japan. Many patients have considerably reduced heart function, such as left ventricular reduced ejection fraction. Approximately half of patients will die within five years of diagnosis, which is worse than some cancers. With no known cure except for heart transplant, a new effective treatment option on top of the current standard of care may offer hope for people struggling with this disease and a new tool for cardiologists,” Masafumi Kitakaze, Director of Hanwa Daini Senboku Hospital, Guest Professor of the Graduate School of Medicine, University of Osaka and Investigator of the DAPA-HF Phase III trial in Japan, said.

“Forxiga’s efficacy in reducing the risk of cardiovascular death or worsening of heart failure events could result in life-saving benefits for many heart failure patients in Japan. Today’s approval will shift the way we manage the disease by providing a treatment option that is urgently needed to improve outcomes and symptoms for these patients,” Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said.

Forxiga is the first sodium-glucose co-transporter 2 (SGLT2) inhibitor to have shown a statistically significant reduction in the risk of the composite of cardiovascular (CV) death or worsening of HF events, including hospitalization for HF (hHF). The DAPA-HF Phase III trial demonstrated that Forxiga, in addition to standard of care, reduced the risk of the composite outcome versus placebo by 26% and both components of the primary composite endpoint contributed benefit to the overall effect.

In the DAPA-HF Phase III trial, the safety profile of Forxiga was consistent with the well-established safety profile of the medicine. During the trial, one CV death or hHF or an urgent visit resulting in intravenous therapy associated with HF could be avoided for every 21 patients treated.

Forxiga (known as Farxiga in the US) is approved in the US, Europe, and several other countries around the world for the treatment of patients with HF with reduced ejection fraction (HFrEF).

Forxiga is advancing cardiorenal prevention as science continues to identify the underlying links between the heart, kidneys and pancreas. DAPA-HF is part of DapaCare, a robust clinical trial program to assess the potential CV and renal benefits of Forxiga. The program has also explored the treatment of patients with chronic kidney disease (CKD) in the ground-breaking DAPA-CKD Phase III trial. Additionally, Forxiga is currently being tested for HF patients with preserved ejection fraction (HFpEF) in the DELIVER Phase III trial with data readout anticipated in the second half of 2021.

In 2013, AstraZeneca K.K. (AZKK), a subsidiary in Japan of AstraZeneca, entered into an agreement with Ono Pharmaceutical for Forxiga. Based on this agreement, Ono is responsible for distribution and marketing of Forxiga tablets in Japan and has been co-promoting it with AZKK for the treatment of T2D and type-1 diabetes. Both companies will co-promote for the treatment of chronic heart failure.

HF affects approximately 64 million people worldwide (at least half of whom have a reduced ejection fraction), including 1.3 million in Japan, 15 million in the EU and six million in the US.2-3,8,9 It is a chronic disease where half of patients will die within five years of diagnosis.10 HFrEF and HFpEF are the two main categories of HF related to ejection fraction, a measurement of the percentage of blood leaving the heart each time it contracts.7 HFrEF occurs when the left ventricle muscle is not able to contract adequately and therefore, expels less oxygen-rich blood into the body.5,6 HF remains as fatal as some of the most common cancers in both men (prostate and bladder cancers) and women (breast cancer).11 It is the leading cause of hospitalization for those over the age of 65 and represents a significant clinical and economic burden.12

DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure) is an international, multi-center, parallel-group, randomized, double-blinded trial in 4,744 patients with HFrEF (LVEF ≤ 40%), with and without T2D, designed to evaluate the effect of Forxiga 10mg, compared with placebo, given once daily in addition to standard of care. The primary composite endpoint was time to the first occurrence of a worsening heart failure event (hospitalization or equivalent event, i.e. an urgent heart failure visit), or CV death. The median duration of follow-up was 18.2 months.

Forxiga (dapagliflozin) is a first-in-class, oral, once-daily SGLT2 inhibitor indicated in adults for the treatment of insufficiently controlled T2D as both monotherapy and as part of combination therapy as an adjunct to diet and exercise to improve glycemic control, with the additional benefits of weight loss and blood-pressure reduction.

Forxiga has been evaluated in patients with CKD in the Phase III DAPA-CKD trial, with the full results announced in August 2020 demonstrating that Forxiga met all primary and secondary endpoints, providing overwhelming efficacy. Forxiga is currently being tested for patients with HF in the DELIVER (HF with preserved ejection fraction, HFpEF) and DETERMINE (HFrEF and HFpEF) Phase III trials. Forxiga will also be tested in patients without T2D following an acute myocardial infarction (MI) or heart attack in the DAPA-MI trial - a first of its kind, indication-seeking registry-based randomized controlled trial. Forxiga has a robust program of clinical trials that includes more than 35 completed and ongoing Phase IIb/III trials in more than 35,000 patients, as well as more than 2.5 million patient-years’ experience.