Amgen revealed new Phase 1 data from AMG 133, a novel bispecific glucose-dependent insulinotropic polypeptide receptor (GIPR) antagonist and glucagon-like peptide-1 (GLP-1) receptor agonist molecule. This first-in-human study was designed to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic effects of AMG 133 in people with obesity and without diabetes. The data were presented at the 20th World Congress of Insulin Resistance, Diabetes and Cardiovascular Disease (WCIRDC) Hybrid Conference.
"AMG 133 was designed based on preclinical and human genetic data that strongly suggest GIPR inhibition as a strategy for weight loss, especially in combination with GLP-1 agonism," said Dr David M Reese, executive vice president of Research and Development at Amgen. "We are encouraged by these Phase 1 results with once-monthly dosing of AMG 133, specifically, the degree, rate and durability of the weight loss. We look forward to initiating the Phase 2 study early next year."
In total, 133 participants were randomised (3:1) to receive subcutaneous AMG 133 or placebo either as a single ascending dose (SAD) or multiple ascending doses (MAD). The MAD cohorts showed mean percent changes in body weight (BW), ranging from -7.2% at the lowest dose (140mg Q4W), to -14.5% at the highest dose (420mg Q4W) by day 85. In addition, a substantial degree of weight loss was maintained beyond the treatment period, which will be shared as part of the oral presentation. Most treatment emergent adverse events (TEAEs) were mild and transient. The majority of the TEAEs were GI-related with the most common being nausea and vomiting, most events resolved within 48 hours.
AMG 133 is a bispecific glucose-dependent insulinotropic polypeptide receptor (GIPR) antagonist and glucagon-like peptide-1 (GLP-1) receptor agonist molecule. AMG 133 mimics the agonist effects of GLP-1 and antagonizes the effects of glucose-dependent insulinotropic polypeptide (GIP). Amgen moved into this Phase 1 study based on human genetic insights and preclinical evidence that suggested synergistic effects with GIP receptor blockade and GLP-1 receptor agonism on weight loss and improvement in other metabolic parameters.
Amgen plans to initiate Phase 2 testing with a dose-ranging study in early 2023, where long-term effects in an expanded number of patients will be further characterised.