Large-scale phase 3 trial shows significant reduction in cardiovascular and kidney disease risk

First public reveal of results from large-scale, Sanofi-led global phase 3 trial for efpeglenatide

Hanmi aims to achieve new innovations with biologic

SEOUL, South Korea, June 29, 2021 /PRNewswire/ -- Hanmi Pharmaceutical (hereinafter Hanmi) recently announced that its new, long-acting diabetes biologic drug, efpeglenatide, was shown to significantly reduce incidences of major adverse cardiovascular events (MACE) and kidney disease in the results of its global, large-scale clinical trial with more than 4,000 patients.

According to Hanmi, Sanofi presented the results of the global, large-scale cardiovascular clinical trial (AMPLITUDE-O) at the "Independent Session on Efpeglenatide", which was held at the American Diabetes Association (ADA) Scientific Sessions on June 29th. During this two-hour session,  Dr. Hertzel Gerstein and seven other researchers presented on eight different topics, respectively, regarding the results from AMPLITUDE-O.

The AMPLITUDE-O phase 3 clinical trial included 4,076 patients with Type 2 diabetes or cardiovascular disease across 344 regions in 28 countries. For the purpose of this trial, either 4mg or 6mg of efpeglenatide or a placebo was administered to patients on a weekly basis.

According to the results, the risk of cardiovascular and kidney disease was significantly reduced in Type 2 diabetes patients who received the 4 mg and 6 mg doses of efpeglenatide. When compared to the placebo group, there was a 27% incidence rate of major cardiovascular diseases [HR: Hazard Ratio 0.73, 95%, confidence interval (CI: confidence interval 0.58 – 0.92)] and a 32% incidence rate of kidney disease (HR 0.68, 95% CI 0.57 - 0.79) in the efpeglenatide group, thus statistically demonstrating that the drug significantly decreases incidences of such diseases.

Naveed Sattar(University of Glasgow, MD, Ph.D.) said "The Amplitude-O trial shows that efpeglenatide safely reduces major cardiovascular and renal outcomes in low and high risk people with type 2 diabetes while lowering glucose, blood pressure and weight"

Seungjae Baek (MD, Ph.D.), Chief Medical Officer at Hanmi, highlighted the promising implications of this study's results. Baek shared, "I would like to think that efpeglenatide has provided us with a new opportunity to achieve innovation in other ways. We are focusing our capacities on expanding upon and realizing the potential of efpeglenatide, whose efficacy has been demonstrated through large-scale, global phase 3 clinical trials."

Efpeglenatide is a once-weekly GLP-1 receptor agonist drug that was developed by Hanmi for the treatment of diabetes mellitus and was licensed out to Sanofi in 2015. Last year, Sanofi returned the rights of efpeglenatide due to changes in the company's business strategy. As such, the rights currently belong to Hanmi.

At this year's ADA meeting, Hanmi also presented the results of another study on the efficacy and safety of efpeglenatide in Type 2 diabetes patients. Lead researcher Dr. Juan Frias presented the results of this study, which involved another global phase 3 clinical trial (AMPLITUDE-M) with 406 Type 2 diabetes patients whose blood sugar could not be managed through diet and exercise.

This study was conducted as a double-blind clinical trial over the course of 56 weeks, with the efpeglenatide group being divided into three subgroups by dosage (2mg, 4mg, and 6mg). The primary endpoint of the trial was glycated hemoglobin (HbA1c) levels at the 30th week. At the 56th week of the trial, HbA1c levels, weight loss, and safety of the efpeglenatide were compared, respectively, with those of the placebo group.

The results of the study confirmed excellent blood sugar control and weight loss when efpeglenatide was administered to Type 2 diabetes patients, and the effects of the treatment were maintained for an extended period of time. At 30 weeks of treatment, when compared to the placebo group, patients across all dosage groups of efpeglenatide showed statistically significant improvement in HbA1c levels compared to those of the placebo group. Patients in the 4mg and 6mg dosage groups also showed significant weight loss. Positive effects of the treatment, such as blood sugar management and weight loss, remained stable for 56 weeks. Reported side effects among participants included mild to moderate diarrhea and nausea.

Furthermore, at the ADA meeting, Hanmi announced the results of four preclinical studies, including its study on ^LAPSGlucagon Analog, a long-acting glucagon-like peptide analog. Hanmi plans to share major ADA announcements on its website.

Se Chang Kwon, President and CEO of Hanmi Pharmaceutical, noted, "Considering that drugs currently sold on the global market for metabolic diseases often possess the risk of cardiovascular disease following long-term observations, cardiovascular safety is crucial in strengthening a given drug's global competitiveness. With the demonstration of efpeglenatide's safety regarding the risk of cardiovascular disease, as demonstrated in this large-scale clinical trial, we have found new business opportunities for innovation."

The clinical outcomes of efpeglenatide published on, a leading international journal, New England Journal of Medicine (NEJM).