October 2, 2018 – The results of the Harmony Outcomes study were published simultaneously in The Lancet.
GSK and the DCRI today announced publication of positive results from the Harmony Outcomes study, which assessed the cardiovascular (CV) safety and efficacy of albiglutide, a GLP-1 receptor agonist, in patients with type 2 diabetes and CV disease. Results were presented at the annual meeting of the European Association for the Study of Diabetes with simultaneous publication in The Lancet.
The study was initiated in July 2015 and GSK remained committed to completing it following an announcement in July 2017 of GSK’s intention to cease further R&D, manufacturing and sales activity for albiglutide (Tanzeum™/Eperzan®). Prior studies of GLP-1 receptor agonists when used in patients with diabetes and CV disease had provided inconsistent results regarding the potential benefit, and GSK believed that the data generated from this study could contribute important new evidence to the field.
Harmony Outcomes was a randomized, double-blind, placebo-controlled study to assess the effect of albiglutide on major adverse CV events in 9,463 patients with type 2 diabetes and cardiovascular disease which took place at 610 sites in 28 countries. Patients were randomized to the addition of once-weekly subcutaneous injection of albiglutide 30mg (potentially increasing to 50 mg) or matching placebo in addition to standard care.
It was hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. The study continued until 611 or more confirmed primary outcome events (CV death, myocardial infarction, or stroke) occurred over a median follow-up of at least 1.5 years.
The primary outcome showed that albiglutide, administered subcutaneously once-weekly in 9,463 patients over a median period of 1.6 years, was superior to placebo in reducing the risk of major adverse cardiovascular events (MACE) by 22 percent (95 percent confidence interval [CI] 10 percent to 32 percent) when used in addition to standard of care in patients with type 2 diabetes and cardiovascular disease (p<0.0001 for non-inferiority; p=0.0006 for superiority). MACE occurred in 7.1 percent (N=338) and 9.0 percent (N=428) of patients receiving albiglutide and placebo in addition to standard of care, respectively. Overall, the number of patients who would need to be treated with albiglutide to prevent one event over a median of 1.6 years was 50.
The incidence of acute pancreatitis was less than 1 percent (10 patients for albiglutide; 7 patients for placebo), as was the incidence of pancreatic cancer (6 patients for albiglutide; 5 patients for placebo). No events of medullary thyroid carcinoma were observed, and other serious adverse events did not differ significantly between the two groups.
“This large cardiovascular outcome trial has shown impressive results for albiglutide in lowering the risk of major adverse cardiovascular events and adds important evidence that certain GLP-1 receptor agonists can improve cardiovascular outcomes,” said the DCRI’s Adrian F. Hernandez, MD, MHS, Duke’s vice dean for clinical research. “Despite the need for treatments to manage these events, there was uncertainty about the cardiovascular effects of GLP-1 receptor agonists as a class due to mixed results from previous studies. We are fortunate that all involved maintained their commitment to participants to complete the trial, which helps address this knowledge gap for patients and clinicians alike on the role of GLP-1 receptor agonists in diabetes.”
“We would like to thank all the investigators and patients who participated in this study,” said GSK’s John Lepore, senior vice president, R&D pipeline. “Harmony Outcomes was an important study for us to complete to generate new data and insights about the role of the GLP-1 receptor agonist class in the management of patients with diabetes and cardiovascular disease. GSK continued to invest in this study following a decision last year to cease all other activities on albiglutide, and we continue to explore opportunities to divest this medicine to a company with the right expertise and resources to realize its full potential for patients.”