AstraZeneca has been granted Fast Track Designation in the US for the development of Farxiga (dapagliflozin) to reduce the risk of hospitalization for heart failure (hHF) or cardiovascular (CV) death in adults following an acute myocardial infarction (MI) or heart attack.

The designation is based on the Phase III DAPA-MI trial that will explore the efficacy and safety of Farxiga in this patient population. Acute MI is a serious condition and a known cause of heart failure (HF). Approximately seven million heart attacks occur globally each year.

The Food and Drug Administration’s (FDA) Fast Track program is designed to accelerate the development and review of new medicines for the treatment of serious conditions where there is an unmet treatment need. In addition to Fast Track Designation, the FDA recently granted Special Protocol Assessment (SPA) agreement to the DAPA-MI trial. The SPA is a rarely granted, advanced declaration by the FDA that a Phase III trial's design is acceptable for a future marketing application.

The DAPA-MI trial integrates routine care and registries with the requirements of a rigorous placebo-controlled, randomized clinical trial, thus aiming for an approvable label indication. Registries are used by physicians to store patient health data collected over time, often during regular recurrent visits. In DAPA-MI, patients and their treating physicians participating in registries can join the trial and integrate it within their routine clinical practice. Unlike conventional studies where patients often need to travel to a trial center that may be far from home, this pragmatic, innovative approach delivers rigorous safety and efficacy data, while reducing patient burden and streamlining trial delivery.

“The Phase III DAPA-MI trial is the first indication-seeking registry-based randomized controlled trial which will provide quicker access to data and reduce recruitment time and cost, while minimizing patient and investigator burden. Today's FDA decision acknowledged the importance of this trial, which will provide valuable insights into Farxiga’s potential in patients who had a heart attack and went on to develop heart failure and also into how we can improve clinical trial design in the future,” Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said.

The DAPA-MI trial is conducted in collaboration with Uppsala Clinical Research Center (UCR) and Myocardial Ischaemia National Audit Project (MINAP) in the UK. It will explore the benefit of Farxiga in patients without type-2 diabetes (T2D) following an acute MI. It is expected to begin recruiting in the fourth quarter of 2020.

In May 2020, Farxiga was approved in the US to reduce the risk of CV death and hHF in adults with HF (NYHA class II-IV) with reduced ejection fraction (HFrEF) with and without T2D. Farxiga is also indicated as an adjunct to diet and exercise to improve glycaemic control in adults with T2D. Additionally, Farxiga is being evaluated for patients with chronic kidney disease (CKD) in the Phase III DAPA-CKD trial, which was stopped early after a Data Monitoring Committee determination of overwhelming efficacy.

Acute MI, also known as a heart attack, is a common, serious condition and cause of HF. The strongest predictor of in-hospital mortality following an acute coronary event is HF. Many patients who experience acute MI will develop HF, and these patients have a higher mortality risk than patients already presenting with HF at admission. The standard of care for patients with acute MI has improved considerably over the years, but the prognosis has not shown a dramatic change indicating that novel approaches are needed to reduce CV risk.

DAPA-MI (DAPAgliflozin effects in patients without diabetes with Myocardial Infarction) is an international, multi-center, double-blinded registry-based randomized controlled trial designed to assess the efficacy and safety of Farxiga 10mg, compared to placebo, given once daily to reduce the risk of hHF and CV disease in adults without T2D following an acute MI. DAPA-MI integrates traditional, pragmatic, and innovative study design elements with the goal of minimizing patient and investigator burden while producing real world evidence of efficacy that adds to the existing body of evidence generated by Farxiga randomized controlled trials. The trial will recruit around 6,400 patients from approximately 50 sites in Sweden and 50 sites in the UK. Prospective data collection is done through two national CV disease quality registries.

Farxiga (dapagliflozin) is a first-in-class, oral once-daily sodium-glucose co-transporter-2 (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 glycaemic control, with the additional benefits of weight loss and blood-pressure reduction. In the DECLARE CV outcomes trial in adults with T2D, Farxiga reduced the risk of the composite endpoint of hHF or CV death versus placebo, when added to standard of care.

Farxiga is also being tested for patients with HF in the DELIVER (HF with preserved ejection fraction, HFpEF) and DETERMINE function and symptom (HFrEF and HFpEF) trials. Farxiga 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.