Viking Therapeutics announced new clinical data from its VK2735 obesity program at ObesityWeek 2024, highlighting the potential of both subcutaneous and oral formulations of the dual GLP-1/GIP receptor agonist for treating metabolic disorders. The data, presented in two poster sessions, included results from the Phase 2 VENTURE trial of subcutaneous VK2735 and the Phase 1 multiple ascending dose (MAD) trial of oral VK2735.
Subcutaneous VK2735: Durable Weight Loss and Potential for Monthly Dosing
The Phase 2 VENTURE trial evaluated weekly subcutaneous injections of VK2735 over 13 weeks in obese patients. Results demonstrated statistically significant reductions in mean body weight, with up to 14.7% weight loss from baseline. Notably, 88% of patients in the VK2735 treatment groups achieved ≥10% weight loss, compared to only 4% in the placebo group. Follow-up data showed that patients maintained the majority of their weight loss four weeks after the final dose (p<0.0001 vs. baseline and placebo). Even seven weeks post-treatment, over 80% of the original weight loss was maintained (p<0.0005 vs. baseline and placebo), suggesting the feasibility of once-monthly dosing for maintenance.
An exploratory analysis revealed that VK2735 treatment increased the likelihood of prediabetic patients returning to normoglycemia during the 13-week treatment period. The safety profile was encouraging, with most treatment-emergent adverse events (TEAEs) being mild or moderate. While nausea was reported in 43% of VK2735-treated patients versus 20% in the placebo group, the majority was mild. Vomiting occurred in 18% of VK2735-treated patients compared to none in the placebo group. The company noted that most gastrointestinal events occurred early in the treatment period and decreased with continued dosing.
Oral VK2735: Promising Weight Loss with Favorable Tolerability
The Phase 1 MAD trial assessed the oral tablet formulation of VK2735, administered daily for 28 days. The study included cohorts receiving doses up to 100 mg. Results showed dose-dependent reductions in mean body weight from baseline, reaching up to 8.2%. Patients also experienced reductions in mean body weight relative to placebo, up to 6.8%. Weight loss effects persisted in follow-up visits through Day 57, with up to 8.3% weight loss from baseline observed four weeks after the last dose.
Up to 100% of VK2735-treated subjects achieved ≥5% weight loss after 28 days, compared to 0% for placebo. The oral formulation also demonstrated encouraging safety and tolerability, with 99% of TEAEs being mild or moderate. Gastrointestinal adverse events were also mostly mild or moderate. Mild nausea was reported in 32% of VK2735-treated subjects versus 11% in the placebo group, with no moderate or severe nausea reported. Vomiting was reported in 4% of VK2735-treated subjects, and diarrhea in 7%, compared to 21% in the placebo group.
Future Directions
Viking Therapeutics plans to discuss the clinical path forward for injectable VK2735 with the FDA later this quarter and expects to initiate a Phase 2 study of the oral tablet formulation by the end of the year. Details of the Phase 3 injectable and Phase 2 oral study designs will be provided closer to study initiation dates.
"We are happy to report the updated results from both the VENTURE Phase 2 study and the oral Phase 1 study," said Brian Lian, Ph.D., chief executive officer of Viking. "We believe the VENTURE data demonstrate VK2735's promising efficacy and tolerability profile through 13 weeks of weekly dosing and support our belief that less frequent dosing regimens may provide effective maintenance of weight control. The updated oral Phase 1 study results continue to demonstrate an encouraging tolerability profile and promising signs of clinical activity at doses of up to 100 mg daily. We believe the durable effects observed following 28 days of dosing suggest potential opportunities to introduce lower dose regimens following an initial induction of weight loss."
