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In November 2021, the National Institute for Health and Care Excellence (NICE) backed NHS on the use of AstraZeneca’s diabetes and heart failure drug Forxiga (dapagliflozin) for the treatment of chronic kidney disease (CKD). Here, Mina Makar, senior vice president, global cardiovascular, renal and metabolism (CVRM), BioPharmaceuticals Business Unit at AstraZeneca, talks about the significance of the drug.
Pharm Exec: Tell us more about the evolution of Forxiga since it wasn’t originally studied for CKD.
Makar: In our early trials with Forxiga, we discovered its efficacy in preventing and delaying cardiorenal disease, while also protecting the organs—important findings given the underlying links between the heart, kidneys, and pancreas. These discoveries led to our Phase III clinical trials DAPA-HF in heart failure with reduced ejection fraction (HFrEF) and DAPA-CKD in CKD, which established Forxiga as the first SGLT2 inhibitor approved for use in these indications.
We drive value outside of the main or first indication to discover where a mode of action can unlock new benefits for patients. For example, we recently announced high-level results from the DELIVER Phase III trial evaluating the efficacy of Forxiga in the treatment of HF patients with left ventricular ejection fraction greater than 40%, and full results will be submitted for presentation at a forthcoming medical meeting. These high-level results coupled with results from DAPA-HF Phase III trial demonstrate Farxiga’s efficacy in HF regardless of ejection fraction.
Pharm Exec: How is Forxiga different than other treatments currently available for CKD?
Makar: CKD impacts nearly 850 million people globally, and diagnosis rates remain low. Additionally, with limited innovation in the past two decades, there is a significant unmet medical need for new and improved treatment options. AstraZeneca is transforming CKD care to drive earlier diagnosis and intervention, and help prevent or slow progression of the disease. Forxiga is the first SGLT2 inhibitor approved for the treatment of CKD regardless of diabetes status.
Pharm Exec: Are there other therapy areas where there is potential for SGTL2 inhibitors? How will these inhibitors fit into AstraZeneca’s research/pipeline going forward?
Makar: Beyond the current indications for Forxiga, we are focused on combining Forxiga with novel compounds to address the complications of CKD earlier on. Our continued investment in research drives data that can be incorporated into clinical practice guidelines to advance patient outcomes. Specifically, two upcoming Phase III trials are evaluating dapagliflozin’s effect on CV death or worsening HF in patients with HFrEF hospitalized for acute HF, and CV death or hospitalization for HF in patients without T2D following an acute myocardial infarction or heart attack, respectively.
Pharm Exec: How did DELIVER underscore Forxiga’s unique ability to treat cardiorenal disease across the spectrum of care?
Makar: As discussed earlier, recent high-level results from the DELIVER Phase III trial showed Forxiga reached a statistically significant and clinically meaningful reduction in the primary composite endpoint of CV death or worsening HF, compared to placebo. Results from the DELIVER and DAPA-HF Phase III trials demonstrate dapagliflozin’s efficacy in heart failure regardless of ejection fraction. Forxiga is already approved in type 2 diabetes, HFrEF, and chronic kidney disease.These positive high-level results from the DELIVER Phase III trial underscore dapagliflozin’s cardiorenal benefits and have the potential to be an important treatment option for patients with HF with mildly reduced (HFmrEF) or preserved ejection fraction (HFpEF), hard-to-treat patient populations in need of more effective treatment options.
Pharm Exec: How important was it to include diversity in your clinical trials?
Makar: Clinical trials must accurately reflect the patient populations we aim to treat; from the conditions they face to the environments in which they live. AstraZeneca is actively contributing to industry and nonprofit partnerships to advance clinical trial diversity, and we are growing and building inclusive local partnerships that are trusted by the communities we need to reach. By the end of 2022, we will also implement our bespoke diversity measurement tool, built on updated data systems and infrastructure, in all new trials.