PR88653

BAGSVÆRD, Denmark, March 24, 2021 /PRNewswire=KYODO JBN/ --

Data presented at ENDO 2021 demonstrate clinically relevant weight loss,

without weight regain, in people treated with semaglutide 2.4 mg vs placebo in

combination with lifestyle intervention.

New results from the STEP phase 3a clinical trial programme demonstrated weight

loss with investigational treatment of once-weekly subcutaneous semaglutide 2.4

mg versus placebo. In the STEP 4 trial, study participants who reached the

maintenance dose of semaglutide 2.4 mg during a 20-week run-in period were

randomised to either continue treatment with semaglutide 2.4 mg or switch to

placebo for 48 weeks.(1) The full results of the STEP 4 trial were presented

today at the virtual Endocrine Society (ENDO) 2021 Annual Meeting and published

in the Journal of the American Medical Association.

"For people with obesity, maintaining weight loss in the long term is

challenging as both physiological and hormonal changes that occur following an

initial weight loss can lead to weight regain. These changes, known as

metabolic adaptation, result in lasting increased levels of hunger and desire

to eat while reducing energy expenditure," said Dr Domenica Rubino, lead

investigator of the STEP 4 trial and Director of Washington Center for Weight

Management and Research. "Like any other chronic disease, obesity requires a

long-term, individualised approach to care, inclusive of medication and

lifestyle components."

Following the 20-week run-in period, people who continued treatment with

semaglutide 2.4 mg for an additional 48 weeks continued to lose weight with a

statistically significant additional mean weight loss of 7.9% (1) (8.8% for the

trial product estimand (2)) from week 20 to week 68. People who were switched

to placebo following the 20-week run-in period regained 6.9% (1) of their body

weight from week 20 to 68 (6.5% for the trial product estimand (2)). The

estimated treatment difference [ETD] for the treatment policy estimand was

-14.8% (95% confidence interval [CI]: -16.0, -13.5; p<0.0001). People who

stayed on semaglutide 2.4 mg throughout the entire 68-week trial achieved a

total weight loss of 17.4% (1) (18.2% for the trial product estimand (2)). Both

treatment groups followed a reduced-calorie diet and increased physical

activity programme throughout the study.(1)

"Obesity is a chronic disease that requires ongoing management and the results

from STEP 4 trial strengthens the evidence around the potential of semaglutide

2.4 mg to transform the medical management of obesity," said Martin Holst

Lange, executive vice president, Development at Novo Nordisk. "Millions of

people living with obesity are in need of additional treatment options to help

them lose weight and keep it off. The results from STEP 4 show that to sustain

weight loss it is important to maintain treatment and that semaglutide 2.4 mg

has the potential to offer sustained weight loss of more than 17% after 68

weeks of treatment."

The semaglutide 2.4 mg safety profile is in line with observations seen

previously with GLP-1 receptor agonists. It is generally well-tolerated, and

the most common adverse events among people treated with semaglutide 2.4 mg

were gastrointestinal events.(1)

About STEP 4 and the STEP clinical trial programme

STEP 4 was a 68-week phase 3a randomised, double-blind, multicentre,

placebo-controlled trial that compared the safety and efficacy of once-weekly

subcutaneous semaglutide 2.4 mg versus placebo on change in body weight. The

trial was designed to assess the effect of continuing versus discontinuing

semaglutide 2.4 mg in 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%). During the 20-week run-in period (Week 0 to Week 20),

participants were treated with semaglutide (16 weeks escalation, followed by 4

weeks at the target dose) as an adjunct to lifestyle intervention (–500

kcal/day diet together with 150 minutes/week of physical activity). Following

the run-in period, the 803 people who reached the maintenance dose of

semaglutide (2.4 mg) reduced their mean body weight from 107.2 kg (Week 0) to

96.1 kg (Week 20) and were randomised (in a 2:1 ratio) to continue treatment

with semaglutide 2.4 mg or switch to placebo for a further 48 weeks (Week 20 to

Week 68) with lifestyle intervention.(2)

The primary endpoint of the trial was the percentage change in body weight from

randomisation (Week 20) to the end of treatment (Week 68). Confirmatory

secondary endpoints included change in waist circumference, systolic blood

pressure, and physical functioning score on the 36-item Short Form Survey

(SF-36), assessed from randomisation (Week 20) to the end of treatment (Week

68). Supportive secondary endpoints included percent change in body weight from

baseline (Week 0) to the end of treatment (Week 68).(2)  

STEP (Semaglutide Treatment Effect in People with obesity) is a phase 3

clinical development programme with once-weekly subcutaneous semaglutide 2.4 mg

in obesity. The global clinical phase 3a programme consists of four trials and

has enrolled approximately 4,500 adults with overweight or obesity.(3)

About subcutaneous semaglutide 2.4 mg for weight management

Once-weekly semaglutide 2.4 mg is under investigation for chronic weight

management and not yet approved for people with obesity. It is currently under

regulatory review in several countries, including the U.S. Food and Drug

Administration (FDA) and the European Medicines Agency (EMA).

Semaglutide is an analogue of the human glucagon-like peptide-1 (GLP-1)

hormone, with 94% similarity to the native human GLP-1 molecule. (4,5)  It

induces weight loss by reducing hunger, increasing feelings of fullness and

thereby helping people eat less and reduce their food cravings.(4)

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,(7) heart disease,(7) obstructive sleep apnoea,(10) non-alcoholic

fatty liver disease(11) and certain types of cancer.(12) The current COVID-19

pandemic has highlighted that obesity also increases the risk for severe

illness and hospitalisation due to COVID-19.(13,14)  

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.(15)  

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 45,000 people in 80 countries and markets its products in around

170 countries. For more information, visit novonordisk.com, Facebook, Twitter,

LinkedIn, YouTube.

References:

1. Domenica R, Abrahamsson N, et al. Weight loss maintenance with once-weekly

semaglutide 2.4 mg in adults with overweight or obesity reaching maintenance

dose. Presented at ENDO Annual Meeting. March 20-23, 2021.

2. Warkentin LM, Das D, Majumdar SR, et al. The effect of weight loss on

health-related quality of life: systematic review and meta-analysis of

randomized trials. Obes Rev. 2014; 15:169–182.

3. 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.

4. Blundell J, Finlayson G, Axelsen M, 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.

5. Lau J, Bloch P, Schaffer L, et al. Discovery of the Once-Weekly

Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide. J Med Chem. 2015;

58:7370-7380.

6. Wadden TA, et al. Intensive Behavioral Therapy for Obesity Combined with

Liraglutide 3.0 mg: A Randomized Controlled Trial. Obesity 2019;21:75–86.

7. WHO. Obesity: Preventing and managing the global epidemic. Available at:

http://www.who.int/iris/handle/10665/42330 Last accessed: March 2021.

8. Peeters A, Barendregt JJ, Willekens F, et al. Obesity in adulthood and its

consequences for life expectancy: a life-table analysis. Ann Intern Med. 2003;

138:24-32.

9. Guh DP, Zhang W, Bansback N, et al. The incidence of co-morbidities related

to obesity and overweight: a systematic review and meta-analysis. BMC Public

Health. 2009; 9:88.

10. Gami AS, Caples SM and Somers VK. Obesity and obstructive sleep apnea.

Endocrinology and Metabolism Clinics of North America. 2003; 32:869-894.

11. Vernon G, Baranova A and Younossi ZM. Systematic review: the epidemiology

and natural history of non-alcoholic fatty liver disease and non-alcoholic

steatohepatitis in adults. Aliment Pharmacol Ther. 2011; 34:274-285.

12. Whitlock G, Lewington S, Sherliker P, et al. Body-mass index and

cause-specific mortality in 900 000 adults: collaborative analyses of 57

prospective studies. Lancet. 2009; 373:1083–1096.

13. Finer N, Garnett SP and Bruun JM. COVID-19 and obesity. Clin Obes. 2020;

10:e12365.

14. Ryan DH, Ravussin E and Heymsfield S. COVID 19 and the Patient with Obesity

- The Editors Speak Out. Obesity (Silver Spring). 2020; 28:847.

15. Durrer Schutz D, Busetto L, Dicker D, et al. European Practical and

Patient-Centred Guidelines for Adult Obesity Management in Primary Care. Obes

Facts. 2019; 12:40-66.

(1)         Based on the treatment policy estimand (primary statistical

approach): treatment effect regardless of treatment adherence or initiation of

other anti-obesity therapies

(2)        Based on the trial product estimand (secondary statistical

approach): treatment effect if all people adhered to treatment and did not

initiate other anti-obesity therapies

SOURCE: Novo Nordisk