Preventing Heart Failure With Farxiga

The FDA has given a Fast Track Designation to accelerate study of how Farxiga may help reduction in mortality and heart failure after a heart attack.

Every year nearly seven million people have heart attacks across the world. Acute myocardial infarction (MI) or heart attack is a known cause of heart failure (H.F.). Patients who experience an MI followed by H.F. will have a higher mortality risk than those who present with H.F. upon hospital admission. New treatments are needed for cardiovascular risk (CV) reduction in this population, and a drug called Farxiga (dapagliflozin) may be the solution. Farxiga is a sodium-glucose 2- inhibitor (SGLT2) and is used as an adjunct to diet and exercise to help patients with type 2 diabetes (T2D) improve their blood sugar. Farxiga, developed by the global pharmaceutical company AstraZeneca, is involved in over 35 trials, including the DELIVER (H.F. with preserved ejection fraction, HFpEF) trial. In 2019, Farxiga was approved by the FDA to reduce the risk of hospitalization for heart failure in patients with type 2 diabetes.

A phase III trial called DAPA-MI will evaluate the safety and efficacy of Farxiga to reduce heart failure risk and mortality after an MI. Due to this trial, the Food and Drug Administration (FDA) has granted Farxiga a Fast Track Designation. The FDA’s 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 May 2020, the FDA gave its Fast Track Designation to AstraZeneca for the development of Farxiga for reduction of CV and hospitalization due to heart failure (hHF) in U.S. patients with heart failure (NYHA class II-IV) and reduced ejection fraction (HFrEF) with or without type 2 diabetes (T2D). A Special Protocol Assessment (SPA) was also granted, allowing the phase III trial to be used for future marketing.

The DAPA-MI study is a multi-center, international, prospective, double-blind registry-based randomized controlled trial. The Uppsala Clinical Research Center (UCR) and Myocardial Ischemia National Audit Project (Minap) in the U.K. collaborate with the trial. It will obtain nearly 6,400 patients from 50 sites in the U.K. and Sweden and start recruiting during the fourth quarter of 2020. The data will be collected through the help of two national CV disease quality registries. The goal of the trial is to explore Farxiga’s benefit after an MI in patients who do not have T2D, by assessing the safety and efficacy of Farxiga 10 mg against placebo given once daily.

Farxiga is not indicated for patients with type 1 diabetes mellitus (T1D) or diabetic ketoacidosis treatment. Hypoglycemia can occur if Farxiga is given with insulin or insulin secretagogues. It is contraindicated in patients with severe renal impairment with an eGFR < 30 mL/min/1.73 m2 with no multiple CV risk factors or established CV disease. Hypotension can occur due to possible volume depletion. Urinary tract infections are common among SGLT2 inhibitors. Farxiga can increase the risk of genital mycotic infections. Life-threatening cases of Fournier’s Gangrene have occurred in patients using Farxiga. Among the adverse effects, female genital mycotic infections seem to be most prevalent with Farxiga 10 mg, according to data collected from 12 placebo-controlled studies.

The importance of Farxiga’s role in reducing mortality and risk of H.F. after an MI is showcased by the Fast Track Designation given by the FDA. AstraZeneca Executive Vice President, Biopharmaceuticals R&D, Mene Pangalos, said, “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.” The trial streamlines delivery and allows for a burden-free collection of data. Farxiga can potentially have a tremendous clinical impact on hospitalization and CV risk reduction in those who experienced an MI.

Practice Pearls:

• The recommended dose for reduction of risk of hospitalization and CV death after an MI in patients with HFrEF is Farxiga 10 mg orally once a day.
• Farxiga is used in adults to help control blood glucose and also for patients with heart failure (when the heart is weak and cannot pump enough blood to the rest of the body) to reduce the risk of CV death and hospitalization for heart failure.
• Fast Track Designations can help provide novel drugs for individuals with severe conditions where there is still a need, like Farxiga and heart failure, followed by an acute MI.

Azpicentral.Com, 2020, https://www.azpicentral.com/farxiga/farxiga.pdf.

“Farxiga Granted Fast Track Designation In The U.S. For Heart Failure Following Acute Myocardial Infarction Leveraging An Innovative Registry-Based Trial Design.” Astrazeneca.Com, 2020.

Zahra Hashemy, PharmD. Candidate, USF Taneja College of Pharmacy