New oral obesity drug safe, linked to weight loss in first-in-human study
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Key takeaways:
- Amycretin, a novel oral obesity drug, was safe and tolerable in a first-in-human study.
- At 12 weeks, patients with obesity taking amycretin lost an average of more than 10% of their body weight.
In a first-in-human study, a novel oral amylin and GLP-1 receptor coagonist was safe and tolerable and lowered weight compared with placebo at 12 weeks in patients with obesity, researchers reported.
Agnes Gasiorek, PhD, MSc Pharm, senior clinical pharmacology specialist at Novo Nordisk, presented the findings of the first-in-human study of amycretin (Novo Nordisk), a unimolecular dual-acting amylin and GLP-1 receptor agonist, at the European Association for the Study of Diabetes annual meeting.
“We are seeing in both clinical and preclinical settings additional benefits when targeting these two biologies,” Gasiorek said during the presentation. “This has led us on to developing our next-generation amylin and GLP-1 receptor agonist ... amycretin, [which] is the first long-acting unimolecular dual agonist engineered to simultaneously target both amylin and GLP-1 receptors with one single molecule.”
The presentation covered the 12-week multiple ascending dose portion of the study, in which 44 participants aged 18 to 55 years with BMI 25 kg/m2 to 39.9 kg/m2 were randomly assigned to dose escalation culminating in amycretin 50 mg per day (n = 16; mean age, 38 years; 75% men; mean BMI, 30.6 kg/m2), amycretin 2 x 50 mg per day (n = 16; mean age, 38 years; 56.3% men; mean BMI, 31.6 kg/m2) or placebo (n = 12; mean age, 42 years; 91.7% men; mean BMI, 30 kg/m2) over 12 weeks.
No significant safety issues
An analysis of the primary endpoint of treatment-emergent adverse events did not reveal any significant safety issues related to amycretin, Gasiorek said during the presentation.
During the 12-week period, treatment-emergent adverse events occurred in 75% of the amycretin 50 mg group, 93.8% of the amycretin 2 x 50 mg group and 33.3% of the placebo group, and all events except one were mild or moderate, she said, noting there was also one serious adverse event in a previous stage of the study.
The most common type of adverse event was gastrointestinal, which occurred in 50% of the amycretin 50 mg group, 87.5% of the amycretin 2 x 50 mg group and 16.7% of the placebo group, Gasiorek said.
“This number of events was mainly driven by mild to moderate nausea, as experienced by approximately 30% to 75% of participants, and single events of vomiting, as reported by appropriately 30% to 50% of participants on active treatment,” she said. “Notably, decreased appetite was also captured as an adverse event, among roughly 50% to 85% of participants on active treatment, which we could just as well term a wanted outcome. In the context of a first-in-human study, these observations were in line with what was expected from targeting these receptors, and no new safety topics occurred during the entire study.”
‘Remarkable’ results
Between baseline and week 12, both amycretin groups lost more body weight than the placebo group (amycretin 50 mg, –10.4%; amycretin 2 x 50 mg, –13.1%; placebo, –1.2%; estimated treatment difference between amycretin 50 mg and placebo, –9.2 percentage points; 95% CI, –12 to –6.5; estimated treatment difference between amycretin 2 x 50 mg and placebo, –11.8 percentage points; 95% CI, –14.6 to –9), Gasiorek said during the presentation.
Those figures are “remarkable for an orally delivered biologic,” she said. “There were no apparent signs of weight loss plateauing during the 12 weeks of treatment; however, it is important to consider that the relatively short treatment duration and limited time on final dose, being 2 weeks only, could potentially introduce bias to this observation.”
She concluded that “the magnitude of weight loss observed after only 12 weeks of daily oral amycretin treatment supports continued evaluation in larger and longer studies to fully assess the safety and efficacy of amycretin in individuals living with overweight, obesity and/or type 2 diabetes.”
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Gasiorek A, et al. OP 13. Presented at: European Association for the Study of Diabetes Annual Meeting; Sept. 9-13, 2024; Madrid.
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