Thu, 05 Nov 2020 10:03:00 -0500
PLAINSBORO, N.J., Nov. 5, 2020 /PRNewswire/ -- Results of a phase 3a trial showed that the investigational drug semaglutide 2.4 mg once-weekly subcutaneous (sc) as an adjunct to intensive behavioral therapy (IBT) demonstrated significantly more body weight loss compared to placebo plus IBT.i The STEP 3 phase 3a trial investigated the efficacy and safety of once-weekly semaglutide 2.4 mg after 68 weeks of treatment compared with placebo both as adjunct to IBTi, which consisted of 30 counselling sessions with a registered dietitian over 68 weeks, plus a reduced-calorie diet and increased physical activity. Trial participants were adults with obesity (BMI ≥30 kg/m2) or overweight (BMI ≥27 kg/ m2) with at least one weight-related comorbidity and without type 2 diabetes (HbA1c <6.5%). An oral presentation of the new data was given today at the ObesityWeek 2020 interactive congress.1
Two distinct statistical approaches to evaluating the effects of semaglutide 2.4 mg were used in the STEP 3 trial: a primary statistical approach that assessed the treatment effect regardless of adherence or use of other anti-obesity therapies, and a secondary statistical approach that evaluated the treatment effect if all participants in the trial adhered to the randomized treatment and did not initiate any other treatment methods.
Based on the primary statistical approach, people treated with once-weekly semaglutide 2.4 mg in addition to IBT lost an average of 16.0% of their body weight from baseline, compared with 5.7% for those who received placebo plus IBT (estimated treatment difference: -10.3 [95% confidence interval: -12.0, -8.6]; p<0.0001). Furthermore, more people treated with semaglutide 2.4 mg plus IBT lost greater than or equal to 5% of their body weight compared to placebo plus IBT (87% vs 48%, respectively).
"Given the multiple weight-loss related challenges faced by people with obesity, patients and practitioners alike need additional medical therapies to support lifestyle interventions, such as IBT, which is a highly intensive weight loss approach," said Professor Tom Wadden, lead investigator and Professor of Psychology in Psychiatry at the Perelman School of Medicine at the University of Pennsylvania. "I'm encouraged to see the significant additional weight loss and improvements in certain cardiometabolic disease risk factors achieved with semaglutide 2.4 mg when added to IBT."
A weight loss of greater than or equal to 10%, 15% and 20% was achieved by 75%, 56% and 36% of those treated with semaglutide 2.4 mg plus IBT respectively, compared to 27%, 13% and 4% of those treated with placebo plus IBT.1 In this trial, semaglutide 2.4 mg plus IBT also demonstrated greater improvements in cardiometabolic risk factors, including waist circumference (-14.6 vs. -6.3 cm) and systolic blood pressure (-5.6 vs. -1.6 mmHg), compared to placebo plus IBT.1
When evaluating the effects of treatment based on the secondary statistical approach, people treated with semaglutide 2.4 mg plus IBT achieved an average weight loss of 17.6%, compared to 5.0% with placebo plus IBT. Additionally, 90% of those who received semaglutide 2.4 mg plus IBT achieved a weight loss of 5% or more after 68 weeks, compared to 50% with placebo plus IBT.1
"Obesity can have a direct impact on health and is linked to many weight-related diseases. There is an unmet medical need to develop treatment options to help people lose weight and keep it off," said Mads Krogsgaard Thomsen, executive vice president and chief scientific officer of Novo Nordisk. "We are delighted with the first full phase 3 results from the STEP trial program, demonstrating that the addition of semaglutide 2.4 mg to IBT can almost triple the magnitude of weight loss achieved with IBT alone, making semaglutide 2.4 mg a meaningful potential future treatment option for people with obesity."
The proportion of participants reporting adverse events was similar in the semaglutide 2.4 mg and placebo groups (95.8% and 96.1%, respectively). The most common adverse events among people treated with semaglutide 2.4 mg were gastrointestinal events (nausea, vomiting, diarrhea and constipation), reported by 82.8% of participants in the semaglutide 2.4 mg group and 63.2% in the placebo group.1 Serious adverse events were reported in 9.1% and 2.9% of participants in the semaglutide 2.4 mg and placebo groups, respectively. The higher rate for semaglutide 2.4 mg was driven by more gallbladder-related serious events and single events unrelated to the treatment.
About semaglutide 2.4 mg for weight management
Once-weekly sc semaglutide 2.4 mg is being investigated by Novo Nordisk as a potential treatment option for obesity. Semaglutide is an analogue of the human glucagon-like peptide-1 (GLP-1) hormone, with 94% similarity to the native human GLP-1 molecule.2,3 It induces weight loss by reducing hunger, increasing feelings of fullness and thereby helping people eat less and reduce their food cravings.2
About STEP 3 and the STEP clinical trial program
STEP 3 was a 68-week phase 3a randomized, double-blind, multicenter, placebo-controlled trial that compared the safety and efficacy of once-weekly sc semaglutide 2.4 mg with placebo when used as an adjunct to IBT (defined as increased physical activity, behavioral support and reduced calorie diet). The trial randomized (in a 2:1 ratio) 611 adults with obesity (BMI ≥30 kg/m2) or overweight (BMI ≥27 kg/ m2) with at least one weight-related comorbidity and without type 2 diabetes (HbA1c <6.5%). The primary endpoints of the trial were change in body weight (%) and proportion of participants who achieved greater than or equal to 5% weight loss, both assessed from baseline to the end of treatment (Week 68). Confirmatory secondary endpoints included: proportion of participants who achieved weight loss greater than or equal to 10% and 15%, and change in waist circumference, systolic blood pressure and physical functioning score on the 36-item Short Form Survey (SF-36), all assessed from baseline to the end of treatment (Week 68).4
STEP (Semaglutide Treatment Effect in People with obesity) is a phase 3 clinical development program with once-weekly sc semaglutide 2.4 mg in obesity. The global phase 3a program consists of four trials and has enrolled approximately 4,500 adults with overweight or obesity.5
Obesity is a chronic, progressive and misunderstood disease that requires long-term medical management.6,7 One key misunderstanding is that this is a disease of willpower, when in fact there is underlying biology that prevents people from losing weight and keeping it off.8 Obesity is influenced by a variety of factors, including genetics, appetite signals, behavior and the environment.8 It is a gateway disease and is associated with at least 60 other health conditions.9 The current COVID-19 pandemic has highlighted that obesity also increases the risk for severe illness and hospitalization due to COVID-19.10,11
The global increase in the prevalence of obesity is a public health issue that has severe cost implications to healthcare systems. In the United States, more than 42% of adults live with obesity.12
About Novo Nordisk
Novo Nordisk is a global healthcare company that's been making innovative medicines to help people with diabetes lead longer, healthier lives for 95 years. This heritage has given us experience and capabilities that also enable us to help people defeat other serious diseases including obesity, hemophilia and growth disorders. We remain steadfast in our conviction that the formula for lasting success is to stay focused, think long-term and do business in a financially, socially and environmentally responsible way. With U.S. headquarters in New Jersey and production and research facilities in six states, Novo Nordisk employs nearly 6,000 people throughout the country. For more information, visit novonordisk.us, Facebook, Instagram and Twitter.
i Included behavioral support and dietician counselling, reduced-calorie diet (with a structured low-calorie diet of 1,000-1,200 kcal/day for the first eight weeks followed by hypo-caloric diet), and increased physical activity of up to 200 minutes per week.
SOURCE Novo Nordisk Inc.