Novo Nordisk Announces Positive Results from Two Early-Stage Trials of AM833 for Obesity Treatment

Compiled by Fan Dongdong

Novo Nordisk Announces Positive Results from Two Clinical Trials of AM833, a Novel Subcutaneous Islet Amyloid PolypeptideRecently, Novo Nordisk announced positive results from two clinical trials of AM833, a novel subcutaneous islet amyloid polypeptide. The two trials were: a Phase 2 monotherapy trial of AM833 and a Phase 1 combination trial with 2.4 mg subcutaneous semaglutide.

AM833 is an acylated, long-acting analog of human islet amyloid polypeptide hormone that induces weight loss by reducing energy intake. This Phase 2, single-blind, monotherapy trial enrolled 706 patients with obesity or overweight who had at least one weight-related comorbidity, to evaluate the safety, tolerability, and efficacy of AM833 for weight management. Patients were randomized to receive once-weekly subcutaneous injections of AM833 at varying doses (0.3 mg, 0.6 mg, 1.2 mg, 2.4 mg, or 4.5 mg), liraglutide (3.0 mg), or placebo, with approximately 100 participants per group. All treatments were administered in conjunction with lifestyle intervention therapy. The mean baseline body weight in the trial was 107.4 kg.

This monotherapy trial ultimately met its primary endpoint. The results demonstrated that the 4.5 mg dose of AM833 achieved a 10.8% reduction in body weight at Week 26, compared with only a 3.0% reduction in the placebo group. The treatment difference between the two groups was statistically significant. Furthermore, AM833 exhibited a favorable safety and tolerability profile throughout the trial.

Another 20-week, multiple ascending-dose Phase 1 clinical trial enrolled 80 participants with obesity or overweight to evaluate the safety, tolerability, pharmacokinetics, and weight-loss potential of AM833 in combination with semaglutide. Semaglutide, a GLP-1 hormone analog, promotes weight loss by reducing hunger and increasing satiety. The results showed that after 20 weeks of treatment, subjects receiving the highest dose achieved a mean weight reduction of 17.1% from a mean baseline weight of 95.1 kg (secondary endpoint).

This trial investigated the number of treatment-emergent adverse events (primary endpoint). AM833 was well tolerated, with the most common adverse events being gastrointestinal disorders, including nausea and vomiting; most symptoms were not severe and were predominantly mild or moderate. The incidence of gastrointestinal side effects observed with the combination of AM833 and semaglutide was comparable to that of semaglutide monotherapy.

Mads Krogsgaard Thomsen, Executive Vice President and Chief Scientific Officer at Novo Nordisk, stated: “The Phase 1 and Phase 2 trial data for AM833 in weight management, particularly when used in combination with semaglutide, further strengthen Novo Nordisk’s obesity treatment portfolio and hold the promise of narrowing the gap between pharmacological therapy and bariatric surgery.”

Reference source: Novo Nordisk successfully completes AM833 phase 2 trial and phase 1 combination trial with AM833 and semaglutide in obesity