Nat Med

Novel agent yields enduring weight loss in phase 1 trial

February 8, 2024

Among participants with obesity in this phase 1, randomized, double-blind, placebo-controlled trial, AMG 133 (maridebart cafraglutide, MariTide) had an acceptable safety and tolerability profile and yielded pronounced dose-dependent weight loss. At the highest dose tested, weight loss was maintained for up to 150 days following the last dose.

• 49 participants were enrolled into seven single-ascending dose (SAD) cohorts, randomized to receive AMG 133 doses ranging from 21 to 840 mg (n = 37) or placebo (n = 12) and followed for up to 150 days. Twenty-six participants were enrolled into three multiple ascending dose (MAD) cohorts, randomized to receive 140, 280 or 420 mg AMG 133 or placebo and followed until day 207. In the MAD cohorts, AMG 133 or placebo was administered SC q4wks on days 1, 29, and 57 for a total of three doses. All participants in the 140 and 280 mg AMG 133 MAD cohorts and the placebo cohort received all three scheduled doses, whereas four out of eight participants in the 420 mg AMG 133 MAD cohort completed all three doses. At the highest MAD dose of 420 mg, four participants withdrew from the study before receiving the second dose after reporting mild GI-related adverse events. Mean baseline BMI ranged from 32.5 to 34.8 kg/m^2 in the SAD cohorts and from 32.5 to 34.2 kg/m^2 in the MAD cohorts. Participants did not have a history of diabetes.
• The highest MAD dose of 420 mg q4wks resulted in a body weight change of −4.9% at day 7 and −14.5% by day 85. In comparison, the placebo group had a mean percent body weight change of 0.04% at day 7 and 1.5% at day 85. Reduction in body weight after three q4wk doses of AMG 133 was maintained through 70 days following the third dose in each group and in the 420 mg group, body weight remained reduced up to −11.2%, 150 days after the last AMG 133 dose.
• Change from baseline BMI followed a similar pattern as the change in body weight. A dose-dependent decrease in waist circumference was observed with MAD doses of 140 mg and 420 mg, whereas fluctuations in waist circumference changes were seen with MAD 280 mg.
• Authors conclude that the safety and tolerability profiles, the longer half-life of AMG 133 allowing for extended dosing intervals, and the magnitude and durability of weight loss seen in this phase 1 trial support continued evaluation of AMG 133 in a phase 2 setting.

Source:

Veniant MM, et al. (2024, February 5). Nat Med. A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings. https://pubmed.ncbi.nlm.nih.gov/38316982/