Viking Therapeutics, Inc. has announced the initiation of a Phase 2 clinical trial for its oral tablet formulation of VK2735, a dual agonist of the glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, aimed at treating obesity and related metabolic disorders. The trial, named VENTURE-Oral Dosing Trial, is designed as a randomized, double-blind, placebo-controlled, multicenter study. It will evaluate the safety, tolerability, pharmacokinetics, and weight loss efficacy of VK2735 when administered as an oral tablet once daily for 13 weeks.
The VENTURE-Oral Dosing Trial plans to enroll approximately 280 adults who are either obese (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with at least one weight-related co-morbid condition. Participants will be evenly randomized to one of six dosing arms or a placebo group. The primary endpoint of the study is the percent change in body weight from baseline after 13 weeks of treatment. Secondary and exploratory endpoints will assess additional safety and efficacy measures.
Prior Clinical Data
Viking previously reported positive results from a 28-day Phase 1 multiple ascending dose (MAD) clinical trial of the tablet formulation of VK2735 in healthy volunteers with a BMI ≥30. The trial demonstrated dose-dependent reductions in mean body weight from baseline, ranging up to 8.2%. Follow-up visits through Day 57 showed persistent weight loss effects, ranging up to 8.3% from baseline, four weeks after the last dose of VK2735 was administered. An exploratory assessment revealed that up to 100% of VK2735-treated subjects achieved ≥5% weight loss, compared with 0% for placebo.
In the MAD trial, oral VK2735 also demonstrated encouraging safety and tolerability through 28 days of once-daily dosing at doses up to and including 100 mg. The majority (99%) of observed treatment emergent adverse events were mild or moderate, with the majority (90%) reported as mild. Similarly, all observed gastrointestinal adverse events were reported as mild or moderate, with the majority (84%) reported as mild.
Development of Subcutaneous Formulation
Concurrent with the development of oral VK2735, Viking is also advancing a subcutaneous formulation of VK2735 through clinical development. The company previously announced positive data from the Phase 2 VENTURE study of subcutaneous VK2735, with the trial successfully achieving its primary and all secondary endpoints. Patients receiving VK2735 demonstrated statistically significant reductions in mean body weight from baseline, ranging up to 14.7%. Statistically significant differences compared to placebo were observed for all doses starting at Week 1 and were maintained throughout the course of the study. Weight loss in all treated cohorts appeared to be progressive through 13 weeks and did not show evidence of plateauing. VK2735 also demonstrated encouraging safety and tolerability in the VENTURE study, with the majority of observed adverse events being reported as mild or moderate. The company plans to initiate Phase 3 development with the subcutaneous formulation of VK2735 in the first half of 2025.
Executive Commentary
"The VENTURE-Oral Phase 2 study represents an important milestone for the VK2735 program as we advance two formulations of this compound into later-stage development," said Brian Lian, chief executive officer of Viking Therapeutics. "Prior 28-day Phase 1 data demonstrated encouraging tolerability with the tablet formulation, as well as promising reductions in body weight. We believe VK2735's clinical results to-date suggest a differentiated profile, with the potential to provide patients and clinicians the option of two well-tolerated formulations, administered by either subcutaneous injection or as a tablet, that each utilize the same active pharmaceutical ingredient. This may reduce the potential risk of unexpected side effects and provide flexibility for use in either the induction of weight loss or for prevention of weight gain, as in a maintenance setting."
