BAGSVÆRD, Denmark, Nov. 6, 2020 /PRNewswire/ -- Results of a phase 3a trial showed that investigational drug semaglutide 2.4 mg once-weekly subcutaneous as an adjunct to intensive behavioural 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 IBT, 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 co-morbidity and without type 2 diabetes (HbA_1c <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 randomised 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).^[1] 

"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 cardiovascular 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. 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 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% of 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 programme, 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."

Semaglutide 2.4 mg was well tolerated and no new safety signals were identified. The most common adverse events among people treated with semaglutide 2.4 mg were gastrointestinal events, as seen in previous trials with GLP-1 receptor agonists.^[1] 

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 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 programme 

STEP 3 was a 68-week phase 3a randomised, double-blind, multicentre, 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, behavioural support, and reduced calorie diet). The trial randomised (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 (HbA_1c <6.5%). The primary endpoint 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 programme with once-weekly sc semaglutide 2.4 mg in obesity. The global phase 3a programme consists of four trials and has enrolled approximately 4,500 adults with overweight or obesity.^[5]

About obesity

Obesity is a chronic disease that requires long-term management.^{[6, 7]} It is associated with many serious health complications and decreased life expectancy.^{[8, 9]} Obesity-related complications are numerous and include type 2 diabetes,^[9] heart disease,^[9] obstructive sleep apnoea,^[10] non-alcoholic fatty liver disease^[11] and certain types of cancer.^[12]  

The global increase in the prevalence of obesity is a public health issue that has severe cost implications to healthcare systems. In 2016, 13% of adults, or approximately 650 million adults, were living with obesity worldwide.^[13] 

About Novo Nordisk 

Novo Nordisk is a leading global healthcare company, founded in 1923 and headquartered in Denmark. Our purpose is to drive change to defeat diabetes and other serious chronic diseases such as obesity and rare blood and endocrine disorders. We do so by pioneering scientific breakthroughs, expanding access to our medicines and working to prevent and ultimately cure disease. Novo Nordisk employs about 44,000 people in 80 countries and markets its products in around 170 countries. For more information, visit novonordisk.com^[1], Facebook^[2], Twitter^[3], LinkedIn^[4], YouTube^[5]. 

References

1. Wadden T, Bailey TS, Billings LK, et al. Semaglutide 2.4 mg and Intensive Behavioral Therapy in Subjects with Overweight or Obesity (STEP 3). Presented at the 38th Annual Meeting of The Obesity Society (TOS) held at ObesityWeek®, November 2–6, 2020 [Oral 084].
2. J Blundell, G Finlayson, M Axelsen, et al. Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes Obes Metab. 2017; 19:1242-1251.
3. J Lau, P Bloch, L Schaffer, et al. Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide. J Med Chem. 2015; 58:7370-80.
4. ClinicalTrials.gov. Research Study to Look at How Well Semaglutide is at Lowering Weight When Taken Together With an Intensive Lifestyle Program (STEP 3). Available at: https://clinicaltrials.gov/ct2/show/NCT03611582^[6]. Last accessed: November 2020.
5. Kushner RF, Calanna S, Davies M, et al. Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5. Obesity. 2020; 28:1050-1061.
6. American Medical Association. A.M.A Adopts New Policies on Second Day of Voting at Annual Meeting. Obesity as a Disease. Available at: http://news.cision.com/american-medical-association/r/ama-adopts-new-policies-on-second-day-of-voting-at-annual-meeting,c9430649^[7]. Last accessed: November 2020.
7. WHO. Obesity: Preventing and managing the global epidemic. Available at: http://www.who.int/iris/handle/10665/42330^[8] Last accessed: November 2020.
8. DP Guh, W Zhang, N Bansback, et al. The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health. 2009; 9:1-20.
9. A Peeters, JJ Barendregt, F Willekens, et al. Obesity in adulthood and its consequences for life expectancy: a life-table analysis. Annals of Internal Medicine. 2003; 138:24-32.
10. AS Gami, SM Caples and VK Somers. Obesity and obstructive sleep apnea. Endocrinology and Metabolism Clinics of North America. 2003; 32:869-94.
11. G Vernon, A Baranova and ZM Younossi. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011; 34:274-85.
12. G Whitlock, S Lewington, P Sherliker, et al. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009; 373:1083–96.
13. World Health Organization. Obesity and Overweight Factsheet no. 311. Available at: http://www.who.int/mediacentre/factsheets/fs311/en/^[9]. Last accessed: November 2020.

[i] Included behavioural 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

References

1. ^{^} novonordisk.com (www.novonordisk.com)
2. ^{^} Facebook (www.facebook.com)
3. ^{^} Twitter (www.twitter.com)
4. ^{^} LinkedIn (www.linkedin.com)
5. ^{^} YouTube (www.youtube.com)
6. ^{^} https://clinicaltrials.gov/ct2/show/NCT03611582 (clinicaltrials.gov)
7. ^{^} http://news.cision.com/american-medical-association/r/ama-adopts-new-policies-on-second-day-of-voting-at-annual-meeting,c9430649 (news.cision.com)
8. ^{^} http://www.who.int/iris/handle/10665/42330 (www.who.int)
9. ^{^} http://www.who.int/mediacentre/factsheets/fs311/en/ (www.who.int)