Novo Nordisk has announced headline results from Semaglutide Treatment Effect in People with obesity (STEP) 1, a phase 3a trial in the STEP programme, which revealed the study met both primary endpoints. STEP 1 is a 68-week randomised, double-blind, multicentre, placebo-controlled weight management trial. The trial investigated the efficacy and safety of once-weekly subcutaneous (sc) semaglutide 2.4mg on body weight over 68 weeks compared to placebo in 1,961 adults with obesity or overweight with comorbidities, both in conjunction with lifestyle intervention.
Once-weekly sc semaglutide 2.4mg is being investigated by Novo Nordisk as a treatment for adults with obesity. Semaglutide is an analogue of the human glucagon‑like peptide-1 (GLP-1) hormone. It induces weight loss by reducing hunger, increasing feelings of fullness and thereby helping people eat less and reduce their calorie intake.
In all people randomised (based on the treatment policy estimand (primary statistical approach): treatment effect regardless of treatment adherence or initiation of other anti-obesity therapies), a statistically significant and superior reduction in body weight was achieved with sc semaglutide 2.4mg, compared to placebo after 68 weeks. People treated with sc semaglutide 2.4mg achieved a weight loss of 14.9%, from a mean baseline body weight of 105.3kg, compared to a 2.4% weight loss with placebo. In addition, 86.4% of those who received sc semaglutide 2.4mg reached a weight loss of 5% or more after 68 weeks, compared to 31.5% with placebo.
When evaluating the effects of treatment taken as intended (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), people treated with sc semaglutide 2.4mg achieved a weight loss of 16.9%, compared to a 2.4% weight loss with placebo after 68 weeks and 92.4% achieved a weight loss of 5% or more, compared to 33.1% with placebo. The treatment differences were statistically significant.
In the trial, sc semaglutide 2.4 mg appeared to have a safe and well-tolerated profile, as seen with previous trials. The most common adverse events among people treated with sc semaglutide 2.4mg were gastrointestinal events. Most events were transient, and mild or moderate in severity.
The STEP is a phase 3 clinical development programme with once-weekly sc semaglutide 2.4mg in obesity. The global clinical phase 3a programme consists of four trials, having enrolled approximately 4,500 adults with overweight or obesity:
- STEP 1 - a 68-week safety and efficacy trial of sc semaglutide 2.4mg versus placebo in 1,961 adults with obesity or overweight.
- STEP 2 - a 68-week safety and efficacy trial of sc semaglutide 2.4mg versus placebo and once-weekly sc semaglutide 1.0mg once-weekly in 1,210 adults with type 2 diabetes and either obesity or overweight.
- STEP 3 - a 68-week safety and efficacy trial of sc semaglutide 2.4mg versus placebo in combination with intensive behavioural treatment in 611 adults with obesity or overweight.
- STEP 4 - a 68-week safety and efficacy trial of sc semaglutide 2.4mg versus placebo in 803 adults with obesity or overweight who reached the target dose of 2.4mg after a 20-week run-in.
“The results from the pivotal STEP 1 trial show that semaglutide 2.4mg provides unprecedented weight loss after 68 weeks. Further, almost all patients achieved a weight loss of at least 5%, which is widely recognised as clinically relevant. The results from this trial are very encouraging, boding well for the treatment outlook for people with obesity,” said Mads Krogsgaard Thomsen, executive vice president and chief science officer of Novo Nordisk. “We now look forward to soon sharing additional data from the remaining two STEP clinical trials.”