GSK announces new 52-week data from phase III study of once-weekly albiglutide in type 2 diabetes

Detailed 52 and 32-week data from the first two Phase III studies of the investigational once-weekly glucagon-like peptide-1 (GLP-1) receptor agonist presented at ADA

Detailed findings from a Phase III study comparing the investigational glucagon-like peptide-1 (GLP-1) receptor agonist albiglutide to prandial insulin (Lispro), were presented today at the American Diabetes Association Meeting (ADA) in Philadelphia, USA, and show that the effect is maintained out to 52 weeks

In Harmony 6,a 52-week randomised open label multicentre study among patients with Type 2 diabetes who were inadequately controlled on intermediate or long-acting insulin, albiglutide (30mg with optional titration to 50mg) was compared to Lispro, each administered in combination with long-acting insulin glargine. As previously disclosed, at 26 weeks, albiglutide showed clinically and statistically significant reductions in HbA1c from baseline and non-inferiority versus Lispro (reduction of 0.82% vs 0.66%; p<0.0001 for non-inferiority) which met the primary endpoint of non-inferiority. The effect on HbA1c was maintained on continued treatment at 52 weeks (reduction from baseline of 1.01% vs 0.85%; p=NS [i]). In addition, t he proportion of patients achieving a clinically meaningful HbA1c target level (ADA goal of <7.0%) by week 52 was 45% in the albiglutide arm compared to 30% (p=NS for treatment difference) in the Lispro arm.

Data presented today also show that weight changes from baseline observed at 26 weeks for patients in the albiglutide arm (-0.73kg loss) vs the Lispro arm (+0.81kg gain) were sustained at 52 weeks (-0.96kg vs +1.66kg; p<0.0001 for treatment difference). Fasting plasma glucose (FPG) decreased from baseline in both study arms throughout the 52 week period (-27mg/dL in the albiglutide arm compared to -16mg/dL in the Lispro arm; p =0.0281 for treatment difference).

Adverse events were higher in the albiglutide arm than the Lispro arm over the 52-week treatment period, with the most common being nausea (13% vs 2%), diarrhoea (14% vs 6%), and injection site reactions (10% vs 5%). No severe hypoglycaemic events (low blood glucose levels) were reported for albiglutide (1% for Lispro) and minor hypoglycaemia (≤70mg/dL) was higher in the Lispro arm compared to the albiglutide arm (39% vs 23%).

Harmony 7 results

Results of Harmony 7, a 32-week head-to-head study comparing albiglutide (50mg) to once-daily liraglutide (1.8mg), were also presented as a poster at the ADA. As previously disclosed, albiglutide demonstrated a statistically significant reduction in HbA1c from baseline (-0.78%; p<0.0001) but did not meet the pre-specified primary endpoint of non-inferiority to liraglutide (-0.99%; 95% CI: 0.08-0.34%; p=NS). The proportion of patients achieving a clinically meaningful HbA1c target level of <7.0 at week 32 was higher in the liraglutide arm (52%) compared to the albiglutide arm (42%; p=0.0023 for treatment difference).

Weight decreased from baseline with both albiglutide and liraglutide, however a greater difference was seen in the liraglutide arm (-2.2kg) vs the albiglutide arm (-0.64kg). FPG change from baseline at week 32 was -22 mg/dL for albiglutide and -30 mg/dL for liraglutide (p=0.0050 for treatment difference).

Overall, adverse events occurred at similar rates in both arms of the study but gastro-intestinal (GI) events occurred more frequently in the liraglutide arm than the albiglutide arm; nausea (29% vs 10%) and diarrhoea (14% vs 15%) were the most common GI adverse events. In the albiglutide treatment group, the incidence of GI events was generally stable from week 1 throughout the study period, with no apparent effect of uptitration at week 6.

Injection site reactions, generally of mild intensity, occurred with greater frequency in the albiglutide arm (13%) vs the liraglutide arm (5%). No severe hypoglycaemic events were reported and minor hypoglycaemia was higher in the liraglutide group compared to the albiglutide (17% vs 13%).

Dr Rickey Reinhardt, Lead Physician, Albiglutide Development Programme, GSK, commented: “These are the first two of eight Phase III clinical trials for albiglutide to be presented, and they will contribute to our overall benefit:risk assessment of once-weekly albiglutide and its role as a potential treatment for patients with type 2 diabetes. Diabetes is a major worldwide public health issue and GSK is fully committed to developing treatment options for the millions of people living with the condition.”

Also presented at the meeting were data from a 16-week Phase IIb study investigating albiglutide in Japanese patients with Type 2 diabetes.

About the Harmony Phase III programme

The Phase III clinical development programme for albiglutide comprises eight individual studies and involvingapproximately 5,000 patients, known as Harmony 1 to Harmony 8. The programme is investigating the efficacy, tolerability and safety, including cardiovascular safety, of albiglutide as mono- and add-on therapy, in patients with type 2 diabetes. The primary efficacy endpoint for all studies is the change from baseline in HbA1c compared to placebo and/or active comparators. A majority of the studies will include active comparators, including a sulphonylurea, a thiazolidinedione (TZD), insulin and a dipeptidyl peptidase four inhibitor (DPP IV).

Harmony 6 & 7 are the first two studies to have completed, and headline data from these trials were first disclosed by GSK on 16 November 2011 (Harmony 7) and 3 April 2012 (Harmony 6). GSK has previously announced that 2-year read-outs from five of the ongoing Phase III studies (Harmony 1 to 5) have also been received and are broadly aligned with the results of the two completed studies. As these five studies will not be completed until early 2013, these data have to remain confidential to protect the integrity of the ongoing blinded studies and in line with our agreement with regulators. These two year data support progression and will be used for regulatory filings. Harmony 8 is due to report later in 2012.

About albiglutide

Albiglutide is an investigational biological, injectable form of human GLP-1. It is not yet approved as a treatment for type 2 diabetes or any other indication anywhere in the world. GLP-1 is a peptide that acts throughout the body to help maintain normal blood-sugar levels and to control appetite. Normally, GLP-1 levels rise during a meal to help the body use and control the elevation in blood sugar levels. However, GLP-1 is rapidly degraded, resulting in its short duration of action. In people with type 2 diabetes, GLP-1 secretion in response to a meal is reduced. Albiglutide is an investigational medicine which fuses human GLP-1 to human albumin. It is designed to extend the action of GLP-1 and has potential to allow for weekly injections.

GSK is developing albiglutide as a once-weekly injection using a fine gauge needle for reconstitution and subcutaneous administration by the patient.