Outcomes from Viking Therapeutics’ Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) clinical trial of VK2735 were presented at ObesityWeek 2023. VK2735 is a novel dual agonist of the glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors in development for the potential treatment of various metabolic disorders such as obesity.
Highlights from the oral presentation include newly reported data demonstrating that 28 days of once-weekly treatment with VK2735 resulted in reductions in subjects' liver fat content and plasma lipid levels, both from baseline and as compared to placebo.
Following 28 days of once-weekly treatment with VK2735, study results demonstrated reductions in liver fat content, both as compared to baseline and as compared to placebo. Subjects receiving VK2735 experienced reductions in liver fat ranging up to 47.2% from baseline.
In the subgroup of study subjects with non-alcoholic fatty liver disease (NAFLD), defined as those with greater than 5% liver fat at baseline, the reductions in liver fat levels were more pronounced. For these subjects, reductions from baseline after four weekly doses ranged up to 49.7%, and placebo-adjusted reductions of up to 58.5% were reported. These results suggest that treatment with VK2735 may provide benefit among patients with NAFLD or non-alcoholic steatohepatitis (NASH).
Notes: 1) MRI-PDFF; all subjects enrolled in MAD portion of study were required to have baseline BMI ≥30 kg/m2. 2) Subjects received escalating weekly doses of 1.5 mg, 3.0 mg, 5.0 mg, 5.0 mg. 3) Least squares mean. 4) Two-sided t test using ANCOVA.
Study investigators also evaluated the change in subjects' levels of plasma lipids, including apolipoprotein B (ApoB), low-density lipoprotein cholesterol (LDL-C), and total cholesterol, following 28 days of once-weekly treatment with VK2735. Dose dependent reductions from baseline in these plasma lipid levels were observed across VK2735 treatment cohorts after four weekly doses. No meaningful changes in levels of high-density lipoprotein cholesterol (HDL-C) were observed following treatment with VK2735.
Notes: *p<0.05 vs. baseline. 1) All subjects enrolled in MAD portion of study were required to have baseline BMI ≥30 kg/m2. 2) Subjects received escalating weekly doses of 1.5 mg, 3.0 mg, 5.0 mg, 5.0 mg.
"These new data demonstrate VK2735's rapid and promising impact on liver fat and plasma lipids on top of the previously reported reductions in body weight," said Dr Brian Lian, chief executive officer of Viking Therapeutics. "We believe these results suggest broader potential benefits on a patient's overall metabolic health, in tandem with weight loss, and may indicate utility in patients with obesity, NAFLD, and NASH. We look forward to building upon the Phase 1 data with results from our ongoing Phase 2 VENTURE study, which is evaluating VK2735's safety and efficacy in patients with obesity over a 13-week treatment period."
The ObesityWeek presentation also highlighted previously reported safety, tolerability and weight loss results from the Phase 1 SAD/MAD trial. In the 28-day MAD portion of the study, VK2735 was well-tolerated and showed positive signs of clinical activity. All MAD cohorts receiving VK2735 experienced reductions in mean body weight from baseline, ranging up to 7.8%. Cohorts receiving VK2735 also demonstrated reductions in mean body weight relative to placebo, ranging up to 6.0%. Statistically significant differences compared to placebo were maintained or improved at the Day 43 follow-up time point, 21 days after the last dose of VK2735 was administered.
The majority of observed adverse events (98%) in the Phase 1 trial were reported as mild or moderate. The majority of GI-specific adverse events (99%) were also reported as mild or moderate. Notably, despite robust activation of the incretin receptor pathways, no hypoglycemia was reported. The company believes that the tolerability data from the Phase 1 study indicate that higher doses may be achieved with longer titration windows.
The Phase 1 trial was a randomised, double-blind, placebo-controlled SAD and MAD study in healthy adults. The SAD portion of the study evaluated VK2735 in healthy adults, while the MAD portion of the study enrolled healthy adults with a minimum body mass index of 30 kilograms per meter squared. The primary objectives of the study were to evaluate the safety and tolerability of single and multiple doses of VK2735 administered subcutaneously and identify suitable doses for further clinical development. The secondary objective was to evaluate the pharmacokinetics of VK2735 in healthy subjects. The SAD portion of the study evaluated escalating single doses of VK2735. In the MAD portion of the study subjects received VK2735 once weekly for 28 days.
Viking is currently conducting the Phase 2 VENTURE trial, a randomised, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics, and weight loss efficacy of VK2735, administered subcutaneously, once weekly, for 13 weeks. The VENTURE trial is evaluating the treatment in 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. The primary endpoint of the study is the percent change in body weight from baseline to Week 13, with secondary and exploratory endpoints evaluating a range of additional safety and efficacy measures.