Date: 2016-04-04
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the Endocrine Society’s 98th Annual Meeting and Expo (ENDO 2016)
Company: Novo Nordisk (Denmark)
Product: Saxenda® (liraglutide 3 mg)
Action
mechanism: peptide/glucagon-like peptide-1 analogue. Saxenda® is a once-daily glucagon-like peptide-1 (GLP-1) analogue with 97% similarity to naturally occurring human GLP-1, a hormone that is released in response to food intake. Like human GLP-1, Saxenda® regulates appetite and lowers body weight through decreased food intake. As with other GLP-1 receptor agonists, liraglutide stimulates insulin secretion and reduces glucagon secretion in a glucose-dependent manner. These effects can lead to a reduction of blood glucose.
Saxenda® was approved by the FDA on 23 December 2014, as an adjunct to a reducedcalorie diet and increased physical activity for chronic weight management in adults with obesity (BMI ?30 kg/m2) or who are overweight (BMI ?27 kg/m2) with at least one weight-related comorbidity. Saxenda® received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) on 22 January 2015.
Disease: treatment of adults with obesity or who are overweight with comorbidities
Therapeutic area: Metabolic diseases
Country:
Trial
details: The SCALE™ (Satiety and Clinical Adiposity?Liraglutide Evidence in Nondiabetic and Diabetic people) Obesity and Prediabetes trial is a randomised, double-blind, placebocontrolled, multinational trial in non-diabetic adults with obesity and non-diabetic adults who are overweight with comorbidities. There were 3,731 participants randomised to treatment with Saxenda® (liraglutide 3 mg) or placebo in combination with reducedcalorie diet and increased physical activity. In addition, participants were further stratified to 56 weeks or 160 weeks of treatment based on prediabetes status at baseline screening. The objectives of this trial were to demonstrate clinically meaningful weight loss at 56 weeks, as well as to investigate the long-term potential efficacy of Saxenda® to delay the onset of type 2 diabetes in participants with prediabetes at baseline screening. It is the largest of the phase 3a trials in the SCALE™ clinical development programme, which encompassed more than 5,000 adults with obesity or adults who are overweight with comorbidities. (NCT01272219)
Latest
news: * On April 4, 2016, Novo Nordisk announced that new data from the three-year part of the phase 3a SCALE™ (Satiety and Clinical Adiposity – Liraglutide Evidence) Obesity and Prediabetes trial were presented at the Endocrine Society’s 98th Annual Meeting and Expo (ENDO 2016 - Fujioka K GF, Krempf M, le Roux C, Vettor R, Shapiro Manning L, Lilleøre S, Astrup A. Liraglutide 3.0 mg Reduces Body Weight and Improves Cardiometabolic Risk Factors in Adults with Obesity or Overweight and Prediabetes: the SCALE Obesity and Prediabetes Randomized, Double-blind, Placebo-controlled 3-year Trial). The three-year part of the trial (n=2,254 adults with obesity or who were overweight with comorbidities and had prediabetes at baseline) data demonstrated that 160 weeks of treatment with Saxenda® (liraglutide 3 mg) (n=1,505) in combination with a reduced-calorie diet and increased physical activity resulted in significant improvements in cardiometabolic risk factors (such as blood pressure and cholesterol) compared with placebo (reduced-calorie diet and increased physical activity alone) (n=749). At week 160, individuals treated with Saxenda® had lost more weight (6.1%) than those treated with placebo (1.9%) (estimated treatment difference [ETD] -4.3% [95% CI -4.9; -3.7], p<0.0001). * On March 8, 2015, Novo Nordisk announced tat new data from the phase 3a SCALE™ Obesity and Prediabetes trial were presented at The Endocrine Society’s 97th Annual Meeting (ENDO), showing that adults with obesity or who are overweight with comorbidities who had lost ?5% of their body weight at 56 weeks (ie weight loss responders), demonstrated greater improvements across a range of efficacy outcomes with Saxenda® (liraglutide 3 mg) treatment in combination with a reduced-calorie diet and increased physical activity, compared with those that had a weight loss of <5% (ie nonresponders). In the SCALE™ Obesity and Prediabetes trial, 63.2% of adults achieved a clinically meaningful body weight reduction of at least 5% with Saxenda® compared with 27.1% on placebo (p<0.0001). The average weight loss for responders on Saxenda® treatment was 11.7% compared with 1.7% for non-responders. For placebo treatment, average weight loss in responders was 10.0% versus 0.1% weight gain in non responders. Saxenda® treatment was associated with a greater reduction in waist circumference in responders, compared with non-responders (11.0 cm vs 3.3 cm).In addition to weight loss, improvements across a number of secondary endpoints were also observed in the responder population (Saxenda® and placebo). A greater improvement was seen in fasting plasma glucose (FPG) in Saxenda® responders compared with placebo responders (-8.3 vs -2.8 mg/dl, respectively) as well as nonresponders (-5.0 vs +1.1 mg/dl, respectively). In addition, treatment with Saxenda® was associated with a greater reduction in systolic blood pressure (SBP) compared with placebo in both responders (-5.5 vs -3.4 mm Hg, respectively) and non-responders (-2.0 vs. -0.8 mm Hg, respectively). Improvements in physical health scores (as measured by the SF-36 questionnaire) were seen with Saxenda® and placebo responders (+4.3 vs +4.1 points, respectively) compared with non-responders (+2.1 vs +1.3 points, respectively). Across the SCALE™ clinical development programme, Saxenda® (liraglutide 3 mg) was generally well tolerated. The most common side effects observed were related to the gastrointestinal system. In the SCALE™ Obesity and Prediabetes trial, rates of adverse
In addition, treatment with Saxenda® achieved results beyond weight loss including improvements in some cardiometabolic risk factors such as blood pressure and cholesterol. At week 160, participants randomised to treatment with Saxenda® experienced a greater reduction in systolic blood pressure compared with placebo (ETD -
2.8 mmHg [-3.8; -1.8], p<0.0001). Those treated with Saxenda® also experienced greater improvements in triglycerides (ETD -6% [-9; -3], p=0.0003) and total cholesterol levels (ETD -2% [-3; 0], p=0.03) compared with placebo. Additionally, people treated with Saxenda® showed a greater reduction in mean waist circumference
compared with placebo (ETD -3.5 cm [-4.2; -2.8]).
In addition, the three-year part of the SCALE™ Obesity and Prediabetes trial met its primary endpoint, demonstrating that continued treatment over three years with Saxenda®, in combination with a reduced-calorie diet and increased physical activity, delayed the onset of type 2 diabetes compared with placebo.Aligned with previous trials, during treatment with Saxenda®, mean pulse rate was increased (ETD +2 beats/min [+1.2; +2.7], p<0.0001). Saxenda® was generally well tolerated, and observed side effects were in line with previous trials.2 Over 160 weeks,
reports of serious adverse events were higher in those treated with Saxenda® compared with placebo (15.1% vs 12.9%). Rates of gallbladder-related adverse events and confirmed acute pancreatitis were low, but more frequent in those treated with Saxenda® (2.9 events per 100 patient-years of observation [PYO] and 0.29/100 PYO, respectively) vs placebo (1.2/100 PYO and 0.13/100 PYO, respectively). The frequency of adjudicated major adverse cardiovascular events was low, and comparable in those treated with Saxenda® and placebo (0.19 vs 0.20 events/100 PYO).
* On May 22, 2015, Novo Nordisk announced the headline results from the SCALE™ Obesity and Prediabetes three-year extension trial in adults with obesity or who were overweight with comorbidities, and had prediabetes at baseline. The trial met its primary endpoint, demonstrating that ongoing treatment with Saxenda® (liraglutide 3 mg) in combination with a reduced-calorie diet and increased physical activity delayed the onset of type 2 diabetes, compared with placebo (diet and exercise alone). Over the course of this 160-week, randomised, blinded phase 3a trial, the time to onset of type 2 diabetes was 2.6 times longer with Saxenda® compared with placebo treatment. In addition, the risk of developing type 2 diabetes was reduced by approximately 80% and statistically significant (p<0.0001) for those being treated with Saxenda®.
events were similar in both responders and non-responders. The number of adverse events leading to trial withdrawal was lower in responders compared with nonresponders.
