Viking Therapeutics Presents New Data from Phase 2b VOYAGE Study of VK2809 in Patients with Biopsy-Confirmed Non-Alcoholic Steatohepatitis (NASH) at The Liver Meeting® 2023

Rhea-AI Summary

Viking Therapeutics, Inc. (NASDAQ: VKTX) announced new results from the Phase 2b clinical trial of VK2809, a liver-selective thyroid hormone receptor beta agonist, in patients with NASH. The study demonstrated statistically significant liver fat reductions from baseline to Week 12 among patients receiving VK2809, with up to 85% experiencing at least a 30% relative reduction in liver fat content. The results also showed comparable liver fat reductions among patients with or without type 2 diabetes, as well as those with F2 or F3 fibrosis. VK2809's potential therapeutic activity is not meaningfully impacted by the presence of type 2 diabetes or patients' stage of fibrosis, indicating its potential benefits across important disease subgroups.

Positive

• VK2809 demonstrated statistically significant reductions in liver fat content among patients with NASH, indicating its potential as a therapeutic intervention for this condition.
• Up to 85% of patients receiving VK2809 experienced at least a 30% relative reduction in liver fat content, a level of reduction associated with a greater likelihood of histologic response in NASH.
• The study showed that VK2809's potential therapeutic activity is not meaningfully impacted by the presence of type 2 diabetes or patients' stage of fibrosis, suggesting its benefits across important disease subgroups.

Negative

• None.

Late Breaking Poster Presentation Reports New Results Demonstrating Robust Liver Fat Reductions Across Key Subgroups, Including Patients with Type 2 Diabetes and Among Those with F2 or F3 Fibrosis

Presentation also Highlights Previously Reported Results Showing Successful Achievement of Study's Primary Endpoint, Statistically Significant Liver Fat Reductions from Baseline to Week 12 Among Patients Receiving VK2809

52-Week Biopsy Results Expected 1H 2024

SAN DIEGO, Nov. 13, 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 the presentation of new results from the ongoing Phase 2b clinical trial of VK2809, the company's novel liver-selective thyroid hormone receptor beta agonist, in patients with biopsy-confirmed non-alcoholic steatohepatitis (NASH). The latest findings from the VOYAGE study were featured in a late breaking poster presentation at the Liver Meeting^® 2023, the annual meeting of the American Association for the Study of Liver Diseases (AASLD), which is being held November 10-14, 2023, in Boston.

As previously reported, the VOYAGE study successfully achieved its primary endpoint, with patients receiving VK2809 experiencing statistically significant reductions in liver fat content from baseline to Week 12 as compared with placebo. Newly reported findings demonstrated robust and comparable liver fat reductions among patients with or without type 2 diabetes, as well as patients with either F2 or F3 fibrosis. These data demonstrate that VK2809's potential therapeutic activity is not meaningfully impacted by the presence of type 2 diabetes or by patients' stage of fibrosis. The data are important as the presence of liver fat and associated lipotoxicity are believed to play a contributing role in the onset and progression of NASH.

Highlights from the AASLD presentation include:

Primary Endpoint: Reduction in Liver Fat Content at 12 Weeks

Patients receiving VK2809 experienced statistically significant reductions in liver fat content, as assessed by magnetic resonance imaging, proton density fat fraction (MRI-PDFF) relative to placebo after 12 weeks of treatment.  The median relative reduction from baseline in liver fat ranged from 38% to 55% for patients receiving VK2809.  Importantly, up to 85% of patients receiving VK2809 experienced at least a 30% relative reduction in liver fat content, a level of reduction that is associated with a greater likelihood of histologic response in NASH.

	Placebo (n = 62)	VK2809 1 mg QD (n = 17)3,4	VK2809 2.5 mg QD (n = 58)	VK2809 5 mg QOD (n = 36)4	VK2809 10 mg QOD (n = 56)
Mean baseline liver fat content	20.4 %	21.7 %	20.2 %	18.4 %	21.5 %
Mean relative change in liver fat by MRI-PDFF1,2	-3.7 %	-16.6% (p=0.082)	-45.3% (p<0.0001)	-36.8% (p<0.0001)	-51.7% (p<0.0001)
Median relative change in liver fat	-5.4 %	-37.5 %	-48.1 %	-42.5 %	-55.1 %
Percentage of patients experiencing ≥ 30% reduction in liver fat2	13.6 %	52.9% (p=0.0015)	77.6% (p<0.0001)	66.7% (p<0.0001)	84.9% (p<0.0001)

Notes: Data from Full Analysis Dataset, defined as all randomized patients who received a baseline and post-baseline MRI. 1) Least squares mean change from baseline using an Analysis of Covariance (ANCOVA) model. 2) p-value vs. placebo. 3) Reduced size cohort intended to identify a minimally effective dose. 4) Enrollment suspended at approximately 50% of target to accelerate study completion.

Among patients with type 2 diabetes, reductions from baseline in liver fat were reported for all VK2809 cohorts, ranging from 36% to 54% at Week 12. The effect size among patients with type 2 diabetes was comparable to that reported for patients without type 2 diabetes. Among non-diabetics, reductions in liver fat from baseline ranged from 19% to 51%. These data suggest that activation of the thyroid hormone beta receptor remains effective at reducing liver fat in the presence of an important metabolic comorbidity commonly observed in patients with NASH.

Mean Reduction in Liver Fat Content at 12 Weeks in Patients With and Without Type 2 Diabetes

	Placebo	VK2809 1 mg QD	VK2809 2.5 mg QD	VK2809 5 mg QOD	VK2809 10 mg QOD
Patients with Type 2 Diabetes	2.1 %	-35.8%*	-43.1%***	-39.5%***	-53.9%***
Patients without Type 2 Diabetes	-6.2 %	-19.4 %	-47.0%***	-33.9%***	-51.2%***

Mean relative % change in liver fat at 12 weeks among patients with and without type 2 diabetes. *p<0.05, ***p<0.001 vs. placebo.

Treatment with VK2809 also demonstrated potent reductions in liver fat content among patients with either F2 or F3 fibrosis. Consistent with the efficacy observed among diabetics and non-diabetics, these data suggest that VK2809 maintains potency across a range of fibrosis stages.

Mean Reduction in Liver Fat Content at 12 Weeks in Patients With F2 or F3 Fibrosis

	Placebo	VK2809 1 mg QD	VK2809 2.5 mg QD	VK2809 5 mg QOD	VK2809 10 mg QOD
Patients with F2 Fibrosis	-7.8 %	-11.0 %	-44.9%***	-38.0%**	-49.2%***
Patients with F3 Fibrosis	-1.6 %	-21.1 %	-40.1%***	-39.0%***	-57.5%***

Mean relative % change in liver fat at 12 weeks among patients with F2 and F3 fibrosis. **p<0.01 vs. placebo, ***p<0.001 vs. placebo.

"We are pleased to see that the impressive efficacy demonstrated by VK2809 for the VOYAGE study's primary endpoint remains consistent across the study's key patient subpopulations.  Neither the presence of type 2 diabetes nor the presence of F2 or F3 fibrosis meaningfully impacted VK2809's efficacy at reducing liver fat. As steatosis and lipotoxicity are believed to be underlying drivers in NASH, these data suggest benefits across important disease subgroups," stated Brian Lian, Ph.D., chief executive officer of Viking. "We look forward to reporting 52-week biopsy data from VOYAGE in the first half of 2024."

Safety and Tolerability

As previously reported, data from the VOYAGE study also confirmed VK2809's encouraging safety and tolerability profile.  After 12 weeks, 94% of treatment related adverse events among patients receiving VK2809 were reported as mild or moderate. As in prior studies, VK2809 demonstrated excellent gastrointestinal tolerability, with rates of nausea, diarrhea, stool frequency, and vomiting similar among VK2809-treated patients compared to placebo. 

Study Design

The VOYAGE study is a randomized, double-blind, placebo-controlled, multicenter, international trial designed to assess the efficacy, safety and tolerability of VK2809 in patients with biopsy-confirmed NASH and fibrosis.  Enrollment included patients with at least 8% liver fat content as measured by MRI-PDFF, as well as F2 and F3 fibrosis.  The study allowed for up to 25% of enrolled patients to have F1 fibrosis provided that they also possess at least one additional risk factor, such as diabetes, obesity or hypertension, among others. The primary endpoint of the study evaluated the change in liver fat content from baseline to Week 12 in patients treated with VK2809 as compared to patients receiving placebo.  Secondary objectives include the evaluation of histologic changes assessed by hepatic biopsy after 52 weeks of treatment.

About VK2809

VK2809 is an orally available, tissue and receptor-subtype selective agonist of the thyroid hormone beta receptor (TRβ) that possesses selectivity for liver tissue, as well as the beta receptor subtype, suggesting promising therapeutic potential in a range of lipid disorders. The compound is currently being evaluated in a Phase 2b clinical trial in patients with biopsy-confirmed non-alcoholic steatohepatitis (NASH) and fibrosis. VK2809 successfully achieved primary and secondary endpoints in a Phase 2a study for the treatment of patients with elevated LDL-C and non-alcoholic fatty liver disease (NAFLD). Selective activation of the thyroid hormone beta receptor in liver tissue is believed to favorably affect cholesterol and lipoprotein levels via multiple mechanisms, including increasing the expression of genes associated with lipid metabolism and clearance.  

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. 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.

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SOURCE Viking Therapeutics, Inc

FAQ

What is the primary endpoint of the VOYAGE study?

The primary endpoint of the study evaluated the change in liver fat content from baseline to Week 12 in patients treated with VK2809 as compared to patients receiving placebo.

What were the highlights from the AASLD presentation?

The highlights included statistically significant reductions in liver fat content among patients receiving VK2809, with up to 85% experiencing at least a 30% relative reduction in liver fat content.

What were the safety and tolerability findings of VK2809?

Data from the VOYAGE study confirmed VK2809's encouraging safety and tolerability profile, with 94% of treatment related adverse events among patients receiving VK2809 reported as mild or moderate.

What is the study design of the VOYAGE study?

The VOYAGE study is a randomized, double-blind, placebo-controlled, multicenter, international trial designed to assess the efficacy, safety and tolerability of VK2809 in patients with biopsy-confirmed NASH and fibrosis.