Viking Therapeutics Announces Positive Top-Line Results from Phase 2b VOYAGE Study of VK2809 in Patients with Biopsy-Confirmed Non-Alcoholic Steatohepatitis (NASH)

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May 16, 2023, 07:00 ET

Study Achieves Primary Endpoint, Demonstrating Statistically Significant Reductions in Liver Fat from Baseline to Week 12 in Patients Receiving VK2809 as Compared to Placebo

Up to 52% Mean Liver Fat Reduction Observed in VK2809-Treated Patients

Up to 85% of Patients Experienced at Least a 30% Relative Reduction in Liver Fat

Statistically Significant Reductions in LDL-C, Triglycerides, and Atherogenic Lipoproteins Observed

Adverse Events, Including GI-Related AEs, Similar Among VK2809-Treated Patients vs. Placebo

Conference Call Scheduled for 8:00 a.m. ET Today

SAN DIEGO, May 16, 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 positive top-line results from its 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 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. The median relative change from baseline in liver fat as assessed by magnetic resonance imaging, proton density fat fraction (MRI-PDFF) ranged from 38% to 55% for patients receiving VK2809. Additionally, VK2809-treated patients demonstrated statistically significant reductions in low-density lipoprotein cholesterol (LDL-C), triglycerides, and atherogenic lipoproteins compared with placebo. The company expects to submit the results for presentation at a future medical conference.

Top-line study results 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 MRI-PDFF, relative to placebo after 12 weeks of treatment. 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 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-

PDFF^1,2

-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.

"These results demonstrate VK2809's impressive potency at reducing liver fat, which we believe represent the largest reductions reported for an oral agent at this stage of development," stated Brian Lian, Ph.D., chief executive officer of Viking. "The high response rates observed in this study suggest improved probabilities of histologic benefit, as has been demonstrated in published clinical studies. In addition, VK2809's consistent effect at reducing plasma lipids provides further support for its role in improving the metabolic profile of patients suffering from NASH. These results align well with those reported from our prior 12-week NAFLD study, but in a more severe population and at lower doses. VK2809's excellent safety and tolerability further establish its best-in-class profile, with rates of drug-related adverse events, including GI-related events such as nausea and diarrhea, that are similar to placebo. We believe these data suggest important benefits for patients with NASH, and look forward to reporting the 52-week biopsy data from this study in the first half of next year."

Reduction in Plasma Lipids

Consistent with prior studies, patients receiving VK2809 demonstrated statistically significant placebo-adjusted reductions in LDL-C ranging from 11% to 20%, as well as statistically significant reductions in triglycerides and atherogenic proteins such as apolipoprotein B (ApoB), lipoprotein (a) [Lp(a)], and apolipoprotein C-III (ApoC-III). Reductions in these plasma lipids improve a patient's overall cardiometabolic profile and may reduce the risk of cardiovascular-related events.

Safety and Tolerability

VK2809 demonstrated encouraging safety and tolerability in this study. The majority (94%) of treatment related adverse events among patients receiving VK2809 were reported as mild or moderate. Discontinuations due to adverse events were low and balanced among placebo and treatment arms. One treatment-related serious adverse event (SAE) was reported in a patient receiving VK2809. A patient with a history of psychiatric disorders reported a worsening of their symptoms. As in prior studies, VK2809 demonstrated excellent gastrointestinal (GI) tolerability in this study. Rates of nausea, diarrhea, stool frequency, and vomiting were similar among VK2809-treated patients compared to placebo.

	Placebo (n = 65)	VK2809 1 mg QD (n = 17)	VK2809 2.5 mg QD (n = 66)	VK2809 5 mg QOD (n = 37)	VK2809 10 mg QOD (n = 61)	VK2809 combined (n=181)
Treatment emergent adverse events, TEAEs (number of subjects, (%))¹	47 (72.3 %)	14 (82.4 %)	52 (78.8 %)	29 (78.4 %)	54 (88.5 %)	149 (82.3 %)
Drug-related TEAEs²	22 (33.8 %)	7 (41.2 %)	13 (19.7 %)	9 (24.3 %)	23 (37.7 %)	52 (28.7 %)
TEAEs leading to study discontinuation	5 (7.7 %)	2 (11.8 %)	1 (1.5 %)	1 (2.7 %)	5 (8.2 %)	9 (5.0 %)
Drug-related GI adverse events	12 (18.5 %)	4 (23.5 %)	3 (4.5 %)	1 (2.7 %)	7 (11.5 %)	15 (8.3 %)
Nausea	5 (7.7 %)	2 (11.8 %)	2 (3.0 %)	1 (2.7 %)	3 (4.9 %)	8 (4.4 %)
Diarrhea	2 (3.1 %)	3 (17.6 %)	2 (3.0 %)	1 (2.7 %)	3 (4.9 %)	9 (5.0 %)

Notes: Study safety population, defined as all patients who were randomized and received at least one dose of study drug. 1) Data as of March 13, 2023. 2) Deemed by investigator as possibly, probably, or definitely related to study drug.

At the 12-week timepoint, there were no numerically or clinically meaningful differences observed in levels of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) among patients receiving VK2809 compared with patients receiving placebo. Similarly, levels of thyroid hormones such as thyroid stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3) were relatively unchanged among VK2809 treated patients compared to patients receiving placebo. Changes in vital signs, including blood pressure, heart rate, and body weight were similar among patients receiving VK2809 as compared to patients receiving 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.

Conference Call Today at 8:00 a.m. ET
Viking will hold a conference call today at 8:00 a.m. ET to discuss the top-line results from the Phase 2b VOYAGE study of VK2809. To participate on the conference call, please dial 844-850-0543 from the U.S. or 412-317-5199 from outside the U.S. In addition, following the completion of the call, a telephone replay will be accessible until May 23, 2023 by dialing 877-344-7529 from the U.S. or 412-317-0088 from outside the U.S. and entering conference ID 2702919. Those interested in listening to the conference call live via the internet may do so by visiting the Investor Relations section of Viking's website at www.vikingtherapeutics.com. An archive of the webcast will be available for 7 days on the company's website at www.vikingtherapeutics.com.

About VK2809

VK2809 is an orally available, tissue and receptor-subtype selective agonist of the thyroid 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 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. Follow Viking on Twitter @Viking_VKTX.

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.

SOURCE Viking Therapeutics, Inc.