AstraZeneca's Farxiga (Dapagliflozin) Fails to Meet Primary Endpoints in Phase III DARE-19 Trial for High-Risk Hospitalized COVID-19 Patients

April 12, 2021 News /Bio ValleyBIOON/ -- Currently, the COVID-19 epidemic overseas is still spreading rapidly. According to Baidu's "Real-time Epidemic Situation of Novel Coronavirus Pneumonia"Big DataReport》, as of 0:00 on April 13, 2021, the global cumulative confirmed cases exceeded 130 million (136.77 million), with more than 2.95 million deaths.

Recently,AstraZeneca(AstraZeneca) and Saint Luke’s Mid America Heart Institute in the United States announced the top-line results from the primary analysis of the global Phase III DARE-19 trial. The trial evaluated the potential of Farxiga (Chinese brand name: Andatang; generic name: dapagliflozin), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, for treating hospitalized patients with COVID-19 who were at risk of developing serious complications.

The results showed that at 30 days, the trial did not achieve statistical significance for either the primary prevention endpoint, which measured organ dysfunction and all-cause mortality, or the primary recovery endpoint, which assessed changes in clinical status (from early recovery to death).During the 30-day trial, the safety and tolerability of Farxiga were consistent with its known safety profile.The full results of the DARE-19 trial will be presented in May 2021 at the American College of Cardiology (ACC) Scientific Sessions.Meetingpublished above.

DARE-19 is the first Phase 3 trial to evaluate the safety and efficacy of SGLT2 inhibitors in hospitalized patients with COVID-19 who are at risk of developing serious complications.Clinical Trial. Risk factors for severe complications in these patients include:Hypertension(HTN), type 2Diabetes(T2D), atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and stage 3-4 chronic kidney disease (CKD). The purpose of this trial is to evaluate whether Farxiga can reduce the risk of disease progression, clinical complications, and death caused by COVID-19 in patients with cardiovascular (CV), metabolic, or renal risk factors.

Cardiac, renal, and metabolic comorbidities are associated with adverse outcomes and mortality in patients with COVID-19. The trial design was informed by substantial evidence regarding Farxiga in heart failure with reduced ejection fraction (HFrEF), chronic kidney disease (CKD), or type 2DiabetesData supporting the protective effects in patients with type 2 diabetes (T2D).

Dr. Mikhail N. Kosiborod, a cardiologist at the Saint Luke’s Mid America Heart Institute and principal investigator of the DARE-19 study, stated, “The DARE-19 study provides important data on the potential benefits and risks of using SGLT2 inhibitors in hospitalized patients with COVID-19. Although the trial did not achieve statistical significance, the findings are highly interesting and valuable and will inform future clinical science. Furthermore, importantly, we observed that dapagliflozin demonstrated a consistent favorable safety profile in the DARE-19 study.”

Mene Pangalos, Executive Vice President of BioPharmaceuticals R&D at AstraZeneca, stated, “Prior to the DARE-19 Phase III trial, there was scant data on the use of SGLT2 inhibitors in hospitalized patients with COVID-19; we have now helped fill this knowledge gap. We look forward to announcing the efficacy and safety data in the coming weeks.”

DARE-19 is an international, parallel-group, randomized, double-blind, placebo-controlled, investigator-sponsored Phase III trial conducted in adult patients hospitalized with COVID-19 at the time of enrollment, who also haveHypertension(HTN), atherosclerotic cardiovascular disease (ASCVD), heart failure with reduced or preserved ejection fraction (HFrEF or HFpEF), type 2Diabetes(T2D), stage III or IV chronic kidney disease (CKD). In the study, all patients received background local standard of care treatment, with the aim of evaluating the impact of Farxiga on the risk of all-cause mortality or disease progression and complications. The primary efficacy endpoint of the study was: time to first occurrence of all-cause death or new-onset/worsening organ dysfunction during a 30-day follow-up period.

The active pharmaceutical ingredient of Forxiga is dapagliflozin, a first-in-class, oral, once-daily selective sodium-glucose cotransporter 2 (SGLT2) inhibitor that has been approved for type 2DiabetesImproving glycemic control in adult patients. This medication acts independently of insulin by selectively inhibiting SGLT2 in the kidneys, thereby helping patients excrete excess glucose through urine. In addition to lowering blood glucose, this drug also possessesWeight Lossand additional benefits of lowering blood pressure. The DECLARE CV outcomes trial conducted in adult patients with type 2 diabetes (T2D) showed that, compared with placebo, Farxiga reduced the risk of the composite endpoint of hospitalization for heart failure (HF) or cardiovascular (CV) death.

Among patients at the highest risk of developing COVID-19 complications, some appear to be those with cardiometabolic diseases. Cardiovascular complications, including acute myocardial injury and heart failure (HF), are common in patients with COVID-19 and seem to be key factors leading to poor prognosis and death, especially in patients with underlying cardiovascular disease and/or chronic kidney disease (CKD). (Bioon.com)

Original Source: Update on the DARE-19 Phase III Trial for Farxiga in COVID-19