VENTURE-Oral Dosing trial: 80% of patients achieve ≥10% weight loss

Viking Therapeutics has announced positive top-line results from the company's Phase 2 clinical trial of the oral tablet formulation of VK2735, the company's dual agonist of the glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. VK2735 is being developed in both oral and subcutaneous formulations for the potential treatment of various metabolic disorders such as obesity.

The Phase 2 VENTURE-Oral Dosing trial successfully achieved its primary and secondary endpoints, with patients receiving VK2735 demonstrating statistically significant reductions in body weight compared with placebo. Additionally, the study showed VK2735 treatment to be safe and well-tolerated through 13 weeks of daily dosing with the majority of treatment emergent adverse events (TEAEs) being categorized as mild or moderate.

Participants receiving once daily doses of the oral tablet formulation of VK2735 demonstrated statistically significant reductions in mean body weight after 13 weeks, ranging up to 12.2% from baseline. Participants receiving VK2735 also demonstrated statistically significant reductions in mean body weight relative to placebo, ranging up to 10.9%. Reductions in body weight were progressive at all doses through the course of the study, with no plateau observed for weight loss at 13 weeks. Statistically significant differences compared to both baseline and placebo were observed for all doses >15 mg starting at Week 1 and continuing throughout the 13-week treatment period.

All doses of VK2735 >15 mg also demonstrated statistically significant differences relative to placebo on the key secondary endpoint assessing the proportion of subjects demonstrating at least 5% and 10% weight loss. Up to 97% of subjects in the VK2735 treatment groups achieved ≥5% weight loss, compared with 10% for placebo, and up to 80% of subjects in VK2735 treatment groups achieved ≥10% weight loss, compared with 5% for placebo.

The oral tablet formulation of VK2735 demonstrated encouraging safety and tolerability following 13 weeks of once-daily dosing. Discontinuation rates due to adverse events in the VENTURE-Oral Dosing study were low and well-balanced among subjects treated with VK2735 compared with placebo. During the study 13% of participants receiving placebo discontinued treatment due to an adverse event, compared with 20% of participants receiving VK2735 treatment. The most common reasons for treatment discontinuation were gastrointestinal (GI)-related adverse events. Overall treatment discontinuation rates were 18% among placebo subjects compared with 28% among VK2735 subjects.

Among subjects receiving VK2735, the majority (98%) of reported drug-related treatment-emergent adverse events (TEAEs) were categorized as mild or moderate in severity. The majority (99%) of TEAEs that were GI in nature were also reported as mild or moderate. Nausea was reported among 58% of participants receiving VK2735 compared with 48% for placebo. Among subjects receiving VK2735, the majority (99%) of reported nausea was characterized as mild or moderate. Vomiting was reported in 26% of VK2735-treated subjects compared with 10% among subjects receiving placebo. GI-related adverse events were generally observed early in treatment, with decreasing frequency upon repeat dosing. Across the combined study arms, the weekly rates of nausea or vomiting did not exceed 5% at any point after the third week of treatment.

The VENTURE-Oral Dosing study included an exploratory dosing cohort designed to assess weight loss maintenance. In this treatment group, participants were rapidly titrated to 90 mg daily doses. After 4 weeks of daily dosing at 90 mg, participants were down-titrated to 30 mg daily doses and maintained at 30 mg daily for 7 weeks. Weight loss in this treatment group was shown to be rapid and progressive through the 90 mg treatment period and was maintained following the transition to 30 mg daily doses. The observed results suggest that effective weight maintenance may also be achieved at doses <30 mg.

The Phase 2 VENTURE-Oral Dosing Trial was a randomised, double-blind, placebo-controlled multicentre study designed to evaluate the safety, tolerability, pharmacokinetics and weight loss efficacy of VK2735 dosed as an oral tablet once daily for 13 weeks. The trial enrolled 280 adults who are obese (BMI ≥30 kg/m2), or adults who are overweight (BMI ≥27 kg/m2) with at least one weight-related co-morbid condition. Enrolled patients were evenly randomized to one of six dosing arms or placebo. The primary endpoint of the study was the percent change in body weight from baseline after 13 weeks of treatment, while secondary and exploratory endpoints evaluated a range of additional safety and efficacy measures.