VK2735, a Dual GLP-1/GIP RA, Showcases Weight Loss Effects in Phase 2 Trial

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Could a new agent be poised to make an entry into the chronic weight management landscape? Phase 2 data from Viking Therapeutics indicates their dual GLP-1/GIP receptor agonist VK2735, which achieved its primary and all secondary endpoints in the trial, could provide an additional option for patients if successful in its phase 3 program.

Results of the phase 2 VENTURE trial, which examined VK2735 relative to placebo in 2.5 mg, 5 mg, 10 mg, and 15 mg dosages, indicate patients using VK2735 15 mg achieved a mean placebo-adjusted body weight reduction of 13.1% at week 13, with 88% of patients in this group achieving a placebo-adjusted weight reduction of 10% or more by week 13.¹

"We are excited to report the top-line results from this important Phase 2 study. VK2735 continues to demonstrate a promising efficacy and tolerability profile following 13 weeks of repeat dosing in obese subjects," said Brian Lian, PhD, chief executive officer of Viking Therapeutics.¹

The development of incretin therapies has become a major point of discussion both inside and outside of healthcare as the popularity and demonstrated benefits of semaglutide and tirzepatide have paved the way for additional agents. Evidencing this trend, the announcement from Viking Therapeutics came just a single day after Boehringer Ingelheim announced phase 2 results from its trial of survodutide, a glucagon/GLP-1 receptor agonist, in patients with metabolic dysfunction-associated steatohepatitis.^2,3

The phase 2 VENTURE trial was a randomized, double-blind, placebo-controlled study aimed at assessing the safety, tolerability, pharmacokinetics, and weight loss efficacy of VK2735 across 4 dosages relative to placebo therapy. A 13-week trial, the study enrolled 176 patients with obesity or who were overweight with at least 1 weight-related comorbidity.¹

The trial’s primary outcome of interest was percent change in body weight from baseline to week 13 among patients treated with VK2735 relative to placebo. The key secondary outcome of interest in the trial was the proportion of patients achieving a 10% or greater reduction in body weight from baseline.¹

Results indicated a mean placebo-adjusted percent change in body weight from baseline ranged from -7.4% with VK2735 2.5 mg (P < .001) to -13.1% with VK2735 15 mg (P < .001). Analysis of the key secondary outcome suggested body weight reductions of 10% or greater were achieved among 39% of the VK2735 2.5 mg group (P=.0036), 62% of the 5 mg group (P =.0002), 70% of the 10 mg group (P < .0001), and 88% of the 15 mg group (P < .0001).¹

Safety analysis of the trial suggested 20% of patients receiving VK2735 discontinued treatment early during the trial. However, the combined discontinuation rate of the VK2735 groups was 13% compared to 14% among the placebo arm. In their release, Viking Therapeutics highlighted 92% of drug-related treatment-emergent adverse events were mild to moderate in severity. The most common adverse events included nausea (VK2735: 43%; placebo: 20%), vomiting (VK2735: 18%; placebo: 0%), constipation (VK2735: 26%; placebo: 11%), and diarrhea (VK2735: 20%; placebo: 9%).¹

In their release, Viking Therapeutics noted plans for the further development of VK2735, including a meeting with the FDA. Additionally, Viking Therapeutics detailed plans to provide phase 1 data from an oral formulation of VK2735 later in the coming weeks.¹

“We look forward to progressing this important therapy into further clinical development later this year. Separately, we remain on track to report data from a Phase 1 study of an oral formulation of VK2735 later this quarter,” Lian added.¹

References:

1. _{^{Viking Therapeutics. Viking Therapeutics announces positive top-line results from phase 2 venture trial of Dual GLP-1/GIP receptor agonist VK2735 in patients with obesity. Viking Therapeutics Investor Room. February 27, 2024. Accessed February 28, 2024. http://ir.vikingtherapeutics.com/2024-02-27-Viking-Therapeutics-Announces-Positive-Top-Line-Results-from-Phase-2-VENTURE-Trial-of-Dual-GLP-1-GIP-Receptor-Agonist-VK2735-in-Patients-with-Obesity.}}
2. _{^{Campbell P. Semaglutide: The drug of today and a steppingstone to Tomorrow. HCP Live. December 6, 2023. Accessed February 28, 2024. https://www.hcplive.com/view/semaglutide-drug-today-steppingstone-tomorrow.}}
3. _{^{Campbell P. Survodutide, a glucagon/GLP-1 ra, reduces MASH in phase 2 trial. HCP Live. February 26, 2024. Accessed February 28, 2024. https://www.hcplive.com/view/survodutide-a-glucagon-glp-1-ra-reduces-mash-in-phase-2-trial.}}