Presentation Highlights Previously Reported Weight Loss of up to 7.8% From Baseline as well as Significant Liver Fat, Plasma Lipid Reductions following 28 Days of Treatment with VK2735
SAN DIEGO, Oct. 17, 2023 /PRNewswire/ -- Viking Therapeutics, Inc. ("Viking") (NASDAQ: VKTX), a clinical-stage biopharmaceutical company focused on the development of novel therapies for metabolic and endocrine disorders, today announced that new results from the company's Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) clinical trial of VK2735 were featured in an oral presentation at ObesityWeek 2023, the annual meeting of The Obesity Society. 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.
Data presented at ObestityWeek 2023 include:
Reduction in Liver Fat Content
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).
Change in Liver Fat Content Following 28 Days of Dosing with VK2735
Multiple Ascending Dose Level | Placebo (n=8) | VK2735 0.5 mg (n=6) | VK2735 1.5 mg (n=6) | VK2735 1.5/3/5/5 mg2 (n=6) | VK2735 3/5/5/7.5 mg (n=6) | VK2735 5/5/7.5/10 mg (n=4) |
Mean baseline liver fat content (%)1 | 6.59 | 2.58 | 7.84 | 8.14 | 11.1 | 3.96 |
Mean percent change from baseline 3 | -0.7 | 3.9 | -24.2 | -24.0 | -47.2 | -8.4 |
p-value vs. placebo4 | - | 0.74 | 0.09 | 0.10 | 0.002 | 0.62 |
NAFLD subset | n=3 | n=0 | n=4 | n=4 | n=4 | n=1 |
Mean baseline liver fat content (%)1 | 12.7 | - | 10.6 | 10.6 | 15.2 | 7.7 |
Mean percent change from baseline 3 | 8.8 | - | -33.8 | -32.5 | -49.7 | -10.7 |
p-value vs. placebo4 | - | - | 0.03 | 0.03 | 0.006 | - |
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.
Reduction in Plasma Lipid Levels
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.
Change in Plasma Lipids Following 28 Days of Dosing with VK2735
Multiple Ascending Dose Level | Placebo (n=9) | VK2735 0.5 mg (n=6) | VK2735 1.5 mg (n=6) | VK2735 1.5/3/5/5 mg2 (n=6) | VK2735 3/5/5/7.5 mg (n=6) | VK2735 5/5/7.5/10 mg (n=4) |
Mean change in Apo(B) from baseline (%)1 | 1.8 | 3.3 | -1.8 | -12.9 | -12.5* | -20.5 |
Mean change in LDL-C from baseline (%) | -9.5 | 1.4 | -10.6 | -13.7 | -20.3* | -23.0 |
Mean change in total cholesterol from baseline (%) | -5.1 | -1.7 | -10.8 | -14.9* | -17.4* | -21.0 |
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 Brian Lian, Ph.D., 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 randomized, 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 randomized, 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.
About GLP-1 and Dual GLP-1/GIP Agonists
Activation of the glucagon-like peptide 1 (GLP-1) receptor has been shown to decrease glucose, reduce appetite, lower body weight, and improve insulin sensitivity in patients with type 2 diabetes, obesity, or both. Semaglutide is a GLP-1 receptor agonist that has been approved by the U.S. Food and Drug Administration and is currently marketed in various dosage strengths and forms as Ozempic®, Rybelsus®, and Wegovy®. More recently, research efforts have explored the potential co-activation of the glucose-dependent insulinotropic peptide (GIP) receptor as a means of enhancing the therapeutic benefits of GLP-1 receptor activation. Tirzepatide is a dual GLP-1/GIP receptor agonist that is currently in clinical development for obesity.
About Viking Therapeutics, Inc.
Viking Therapeutics is a clinical-stage biopharmaceutical company focused on the development of novel first-in-class or best-in-class therapies for the treatment of metabolic and endocrine disorders, with three compounds currently in clinical trials. Viking's research and development activities leverage its expertise in metabolism to develop innovative therapeutics designed to improve patients' lives. The company's clinical programs include VK2809, a novel, orally available, small molecule selective thyroid hormone receptor beta agonist for the treatment of lipid and metabolic disorders, which is currently being evaluated in a Phase 2b study for the treatment of biopsy-confirmed non-alcoholic steatohepatitis (NASH) and fibrosis. In a Phase 2a trial for the treatment of non-alcoholic fatty liver disease (NAFLD) and elevated LDL-C, patients who received VK2809 demonstrated statistically significant reductions in LDL-C and liver fat content compared with patients who received placebo. The company is also developing VK2735, a novel dual agonist of the glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors for the potential treatment of various metabolic disorders. Data from a Phase 1 trial evaluating VK2735 (dosed subcutaneously) for metabolic disorders demonstrated an encouraging safety and tolerability profile as well as positive signs of clinical benefit. The company also recently initiated a Phase 1 study to evaluate an oral formulation of VK2735. In the rare disease space, the company is developing VK0214, a novel, orally available, small molecule selective thyroid hormone receptor beta agonist for the potential treatment of X-linked adrenoleukodystrophy (X-ALD). VK0214 is currently being evaluated in a Phase 1b clinical trial in patients with the adrenomyeloneuropathy (AMN) form of X-ALD. The company holds exclusive worldwide rights to a portfolio of five therapeutic programs, including VK2809 and VK0214, which are based on small molecules licensed from Ligand Pharmaceuticals Incorporated.
For more information about Viking Therapeutics, please visit www.vikingtherapeutics.com.
Forward-Looking Statements
This press release contains forward-looking statements regarding Viking Therapeutics, Inc., under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, including statements about Viking's expectations regarding its clinical and preclinical development programs and cash resources. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially and adversely and reported results should not be considered as an indication of future performance. These risks and uncertainties include, but are not limited to: risks associated with the success, cost and timing of Viking's product candidate development activities and clinical trials, including those for VK2735, VK0214, VK2809, and the company's other incretin receptor agonists; risks that prior clinical and preclinical results may not be replicated; risks regarding regulatory requirements; and other risks that are described in Viking's most recent periodic reports filed with the Securities and Exchange Commission, including Viking's Annual Report on Form 10-K for the year ended December 31, 2022, and subsequent Quarterly Reports on Form 10-Q, including the risk factors set forth in those filings. These forward-looking statements speak only as of the date hereof. Viking disclaims any obligation to update these forward-looking statements except as required by law.
SOURCE Viking Therapeutics, Inc