Date: 2014-11-04
Type of information: Presentation of results at a congress
phase: 3a
Announcement: presentation of results at Obesity Week 2014, the 2nd Annual Congress of The American Society for Metabolic and Bariatric Surgery and The Obesity Society
Company: Novo Nordisk (Denmark)
Product: liraglutide 3 mg
Action
mechanism: Liraglutide 3 mg is a once-daily GLP-1 analogue with 97% homology to human GLP-1. Like human GLP-1, liraglutide 3 mg acts as a natural satiety hormone to reduce appetite and food intake. Liraglutide 3 mg is not an approved treatment.
Liraglutide is currently approved and marketed at lower doses (1.2 and 1.8 mg once-daily as well as 0.9 mg in Japan) for type 2 diabetes only, under the brand name Victoza®. Victoza® is not approved for weight management and should not be prescribed for its treatment.
Disease: induction and maintenance of weight loss in overweight or obese people with type 2 diabetes
Therapeutic area: Metabolic diseases
Country:
Trial
details: SCALE (Satiety and Clinical Adiposity - Liraglutide Evidence in Non-diabetic and Diabetic people) consists of four trials of approximately 5,000 people who are overweight (BMI ≥27 kg/m2) and with comorbidities such as hypertension, dyslipidaemia, or type 2 diabetes or who are obese (BMI ≥30 kg/m2) with or without comorbidities. In addition to demonstrating safety and efficacy for weight management with liraglutide 3 mg, each of the four trials has its own distinct focus: SCALE Obesity and Pre-diabetes (3,731 people randomised)- a 56-week and 160- week randomised, placebo-controlled trial in obese or overweight people with comorbidities designed to demonstrate clinically meaningful and safe weight loss after 56 weeks of treatment with liraglutide 3 mg. SCALE Sleep apnoea (approximately 340 people randomised) - a 32-week randomised, double-blind, placebo-controlled trial in obese people with moderate or severe obstructive sleep apnoea (OSA) to investigate the effect of liraglutide 3 mg in reducing the severity of OSA, in combination with diet and exercise.
SCALE Maintenance (422 people randomised) - a 56-week randomised, placebo-controlled trial designed to show weight loss maintenance in obese or overweight people with comorbidities who have successfully achieved a 5% or greater weight loss during a three month run-in period of a lifestyle modification programme of low calorie diet and exercise alone. The results of SCALE Maintenance were reported in 2010.
SCALE Diabetes (846 people randomised) - a 56-week randomised, placebo-controlled trial designed to demonstrate clinically meaningful and safe weight loss with liraglutide 3 mg in obese or overweight people with type 2 diabetes. It was designed to demonstrate clinically meaningful weight loss with liraglutide 3 mg in this population.
Latest
news: * On November 4, 2014, new data from the phase 3a SCALE™ Obesity and Prediabetes trial were presented at Obesity Week 2014, the 2nd Annual Congress of The American Society for Metabolic and Bariatric Surgery and The Obesity Society. 92% (9 out of 10) of trial participants lost weight with liraglutide 3 mg treatment, in combination with diet and exercise, compared with 65% on placebo treatment. People who completed the trial (56 weeks) demonstrated significantly greater weight loss of 9.2% compared with a 3.5% reduction in the placebo group (estimated difference [ED] 5.7%, p<0.0001). In addition, weight loss with liraglutide 3 mg was similar across a range of baseline body mass index (BMI) subgroups in people with obesity, from overweight to Class III obesity,* at 56 weeks (p=0.054, %; p=0.54, kg) and independent of prediabetes status at screening (-8.0% with vs -7.9% without, p=0.59). A larger proportion of people treated with liraglutide 3 mg completed the trial compared with those on placebo (72% vs. 64%). All treatment groups followed a reduced-calorie diet and an increased physical activity programme. Weight loss associated with liraglutide 3 mg was accompanied by improvements in health-related quality of life (HRQoL) as measured by three different questionnaires. Greater improvements were seen with liraglutide 3 mg vs placebo.2 The Impact of Weight on Quality of Life-Lite (IWQoL), total score improved mostly due to better physical function. Both the Short-Form (36) Health Survey (SF-36)4 summary of physical scores and mental health scores improved. In addition, the total Treatment Related Impact Measure-Weight (TRIM-W)5 score was better at 56 weeks with liraglutide 3 mg compared with placebo treatment. * On June 4, 2014, Novo Nordisk announced that primary results from SCALE™ Diabetes were presented at the 74th Annual Scientific Sessions of the American Diabetes Association (ADA) in San Francisco, California. Liraglutide 3 mg, in combination with diet and physical activity, demonstrated statistically significantly greater weight loss at 56 weeks in adults with obesity and type 2 diabetes or who were overweight with type 2 diabetes, compared with placebo. All treatment groups included a reduced-calorie diet and increased physical activity. At 56 weeks of treatment, the SCALE™ Diabetes trial showed that adults treated with liraglutide 3 mg achieved significantly greater mean weight loss of 5.9% of baseline body weight compared with 4.6% with liraglutide 1.8 mg (P<0.01), and 2.0% with placebo (P<0.0001). In the trial, 49.9% of people achieved clinically meaningful weight loss of at least 5% when treated with liraglutide 3 mg compared with 35.0% treated with liraglutide 1.8 mg (P<0.001) and 12.7% with placebo (P<0.0001). The proportion of people losing more than 10% body weight was significantly greater with liraglutide 3 mg (22.1%) compared with liraglutide 1.8 mg (13.3%) and placebo (3.8%) (P * On May 16, 2014, Novo Nordisk has announced that results from the SCALE™ Obesity and Pre-diabetes phase 3a trial will be presented on May 16, 2014, for the first time at the 23rd Annual Congress of the American Association of Clinical Endocrinologists (AACE). Data showed that after 56 weeks of treatment, liraglutide 3 mg, in combination with diet and exercise, provided significantly greater weight loss of 8% from baseline compared to 2.6% with placebo (P). This is the largest trial in the SCALE™ program investigating liraglutide 3 mg, an investigational once-daily glucagon-like peptide-1 (GLP-1) analogue for weight management. All treatment arms included a reduced-calorie diet and increased physical activity. The proportion of adults achieving weight loss of 5% or more of their baseline body weight was 64% for liraglutide 3 mg treatment compared to 27% for placebo (P). In addition, 33% of adults treated with liraglutide 3 mg achieved weight loss greater than 10% of their baseline body weight compared to 10% for placebo (P). In conjunction with weight loss, treatment with liraglutide 3 mg significantly reduced waist circumference by -8.19 cm, compared to -3.94 cm with placebo (P). Furthermore, treatment with liraglutide 3 mg improved blood glucose levels, blood pressure and lipids levels. The most frequently reported side effects associated with liraglutide 3 mg treatment were gastrointestinal (nausea and diarrhea), which were mild to moderate, occurred shortly after liraglutide initiation, and were transient. Incidences of gallbladder disorders and pancreatitis were low but higher than in placebo-treated individuals. Gallbladder disorders were reported as 2.7 events per 100 patient-years of exposure (PYE) with liraglutide 3 mg treatment compared to 1.0 events per 100 PYE for placebo, and pancreatitis as 0.3 events per 100 PYE with liraglutide 3 mg compared to 0.1 events per 100 PYE with placebo. In December 2013, Novo Nordisk submitted a New Drug Application to the FDA and a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for liraglutide 3 mg for chronic weight management in adults who have obesity (BMI >30 kg/m2), or are overweight (BMI >27 kg/m2) with comorbidities, as an adjunct to a reduced-calorie diet and increased physical activity.[1] These applications are under review. * On May 23, 2013, Novo Nordisk has announced the headline results from a 56-week double-blind phase 3a clinical trial investigating the potential of liraglutide to induce and maintain weight loss in people without diabetes who are obese or overweight with comorbidities such as prediabetes, hypertension and dyslipidaemia. This is the third phase 3a trial to be completed as part of SCALE™, the clinical development programme for liraglutide 3 mg as an obesity treatment.
In the trial, 3,731 overweight or obese people were randomised 2:1 to treatment with liraglutide 3 mg or placebo, both in combination with diet and exercise. In the trial, people without signs of prediabetes were treated for 56 weeks, followed by a 12-week follow-up period. People with signs of prediabetes at the time of randomisation are currently continuing treatment for two additional years. The announced results are for all people at 56 weeks.
From a mean baseline weight of 106 kg and a BMI of 38 kg/m2, the average weight loss for people treated with liraglutide 3 mg at 56 weeks was 8.0% compared to 2.6% for people treated with placebo. The proportion of people achieving a weight loss of at least 5% was 64% for liraglutide 3 mg and 27% for placebo. The proportion of people achieving a weight loss of at least 10% was 33% for liraglutide 3 mg and 10% for placebo treatment. All differences between liraglutide and placebo were statistically significantly different and the trial met all three co-primary endpoints.
Of all people participating in the trial, 61% had prediabetes at randomisation. At 56 weeks, 69% of the prediabetes subgroup treated with liraglutide 3 mg no longer showed signs of prediabetes, compared to 33% for the placebo-treated group. Of the 39% of the people without prediabetes at randomisation, 7% of the liraglutide 3 mg treated people developed prediabetes, compared to 21% of the people in the placebo group. Both differences between liraglutide 3 mg and placebo were statistically significant.
Finally, people treated with liraglutide 3 mg experienced statistically significant improvements in obesity-related risk factors, including blood pressure, cardiovascular risk biomarkers, lipids and patient-reported quality of life, compared to people treated with placebo.
In the trial, liraglutide was generally well tolerated. The 56-week completion rate was 72% and 64% for liraglutide 3 mg and placebo, respectively. Withdrawals due to adverse events were below 10% in both treatment groups. The most common adverse events were related to the gastrointestinal system and they diminished over time.
Novo Nordisk expects to complete the remaining phase 3a trial in the SCALE™ programme in the third quarter of 2013 and to file liraglutide 3 mg for regulatory review as a treatment for obesity in the US and EU around the turn of the year.
* On 18 March 2013, Novo Nordisk has announced the headline results from a 56-week, double-blind phase 3a clinical trial investigating the potential of liraglutide to induce and maintain weight loss in overweight or obese people with type 2 diabetes. This is the second phase 3a trial to be completed as part of SCALE™.
In the trial, 846 overweight or obese people with type 2 diabetes were randomised 2:1:1 to treatment with liraglutide 3 mg, liraglutide 1.8 mg or placebo. After 56 weeks, treatment was discontinued and the subjects were followed during a 12-week observational period.
Results regarding weight loss: From a mean baseline weight of approximately 106 kg and a BMI of 37, the weight loss for people treated with liraglutide 3 mg and liraglutide 1.8 mg after 56 weeks were 6% and 5%, respectively compared to a 2% weight loss for people treated with placebo. The proportion of people achieving a weight loss of at least 5% or 10% was 50% and 22% for liraglutide 3 mg, 35% and 13% for liraglutide 1.8 mg, and 13% and 4% for placebo treatment. All differences for both doses of liraglutide were statistically significantly different from placebo and the trial met all three co-primary endpoints. During the 12-week follow-up period after treatment discontinuation, people in both liraglutide treatment groups experienced a moderate weight regain.
Results regarding glycaemic control: Starting from a baseline HbA1C of 8.0%, approximately 69%, 67% and 27% of people treated with liraglutide 3 mg, liraglutide 1.8 mg and placebo achieved the HbA1c treatment target of 7% recommended by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). In the trial, the rate of hypoglycaemia was comparable to that observed in previous trials with liraglutide.
In the trial, liraglutide was generally well tolerated and the 56-week completion rate was 77%, 78% and 66% for liraglutide 3 mg, liraglutide 1.8 mg and placebo, respectively. Withdrawals due to adverse events were below 10% in all treatment groups. In line with previous liraglutide trials, the most common adverse events were related to the gastrointestinal system and diminished over time. No other apparent differences between the treatment groups were observed with respect to adverse events and standard safety parameters.
Novo Nordisk expects to complete the two remaining phase 3a trials in the SCALET programme by mid-2013.
