Novo Nordisk's GLP-1 Agonist Semaglutide Demonstrates Significant Efficacy in Obesity Treatment: 18.2% Weight Loss Over 68 Weeks

March 23, 2021/BioonBIOON/--Novo Nordisk recently announced at the 2021 Endocrine Society Annual Meeting (ENDO 2021) the results of the STEP 3a Phase trial evaluating subcutaneous semaglutide 2.4 mg for the treatment of obesity.Clinical TrialsLatest Results of the Project. Data from the STEP 4 trial showed that once-weekly subcutaneous (SC) injection of semaglutide at a dose of 2.4 mg resulted in a statistically significant reduction in body weight compared with placebo.

Obesity is a chronic disease requiring long-term treatment, and it is associated with many serious health consequences and reduced life expectancy. There are numerous obesity-related complications, including type 2Diabetes, heart disease, obstructive sleep apnea, chronic kidney disease, non-alcoholic fatty liver disease, and cancer.

Currently, Novo Nordisk is developing a once-weekly 2.4 mg subcutaneous injection formulation of semaglutide as a treatment for obesity in adults. Semaglutide is a glucagon-like peptide-1 (GLP-1) analog that helps people eat less and reduce calorie intake by reducing hunger and increasing satiety, thereby inducingWeight Loss。

The STEP program (Semaglutide Treatment Effect in People with obesity) is a global Phase IIIa clinical development program evaluating once-weekly subcutaneous (SC) semaglutide at a 2.4 mg dose for weight management in adult patients with obesity. The program comprises four Phase IIIa trials, which have enrolled approximately 4,500 adults with overweight or obesity, and all trials have achieved successful outcomes.

Based on data from the STEP clinical program, Novo Nordisk submitted to the U.S. in December 2020FDAA New Drug Application (NDA) was submitted for semaglutide 2.4 mg subcutaneous injection, administered once weekly for long-term weight management. Notably, Novo Nordisk also submitted a Priority Review Voucher (PRV) to expedite the NDA review, which can shorten the review timeline from the standard 10 months to 6 months.

The indication applied for the 2.4 mg subcutaneous injection formulation of semaglutide is: as an adjunct to a reduced-calorie diet and increased physical activity, for the treatment of adult patients with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with at least one weight-related comorbidity.

STEP 4 (Withdrawal) was a 68-week, randomized, double-blind, multicenter, placebo-controlled withdrawal trial that enrolled a total of 902 patients with obesity or overweight and comorbidities to compare the efficacy and safety of semaglutide versus placebo for sustained weight management. The trial comprised a 20-week run-in period and a 48-week maintenance period. During the 20-week run-in period, 803 patients reached the target dose of 2.4 mg following dose escalation of semaglutide, with mean body weight decreasing from 107.2 kg to 96.1 kg. Subsequently, these patients entered the maintenance period and were randomized into two groups: one group received once-weekly subcutaneous (SC) semaglutide 2.4 mg, and the other received once-weekly SC placebo, for a duration of 48 weeks. Throughout the study, both treatment groups adhered to a regimen of reduced-calorie diet and increased physical activity.

This trial employed two statistical methods: (1) treatment strategy-based evaluation (the primary statistical method), which does not consider treatment adherence or the initiation of otherWeight Losstherapeutic efficacy of the drug; (2) based on the per-protocol set analysis (secondary statistical method), i.e., all patients adhered to the study medication and did not initiate otherWeight LossTherapeutic efficacy of the drug.

The results showed that the STEP 4 trial met both primary endpoints, with data demonstrating statistically significant differences: patients who continued treatment with subcutaneous semaglutide 2.4 mg experienced further substantial weight loss, whereas those switched to placebo exhibited significant weight regain.

— Key statistical methods showed that among all randomized patients, those who continued treatment with subcutaneous (SC) semaglutide 2.4 mg for 48 weeks experienced a further mean weight reduction of 7.9% from the baseline at randomization (weight at the end of the run-in period); whereas patients receiving placebo had a mean weight increase of 6.9% from the baseline at randomization. The difference between the two treatment groups was statistically significant. Patients who received continuous once-weekly SC semaglutide treatment for 68 weeks (20-week run-in period + 48-week maintenance period) achieved a mean weight reduction of 17.4%.

—Secondary statistical analyses showed that among patients in the intention-to-treat population, those who continued treatment with subcutaneous (SC) semaglutide 2.4 mg for 48 weeks achieved a further mean weight reduction of 8.8% from the baseline at randomization (weight at the end of the run-in period); whereas patients receiving placebo experienced a mean weight increase of 6.5% from the baseline at randomization. The difference between the two treatment groups was statistically significant. Patients who received continuous once-weekly SC semaglutide treatment for 68 weeks achieved a mean weight reduction of 18.2%.

In this trial, once-weekly subcutaneous injection of semaglutide 2.4 mg demonstrated a safety profile consistent with that previously observed for GLP-1 receptor agonists and was well tolerated. Among patients receiving semaglutide 2.4 mg, the most common adverse events were gastrointestinal disorders. (Bioon.com)

Original Source: Adults with obesity treated with semaglutide 2.4 mg achieved and maintained a significant amount of weight loss in a 68-week trial