Viking Therapeutics Presents Results from Phase 2 Study of VK2809 in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD) and Elevated LDL-Cholesterol in Oral Late-Breaker Presentation at The Liver Meeting® 2018

SAN DIEGO, Nov. 12, 2018 /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 results from the company's 12-week Phase 2 study of VK2809, its novel liver-selective thyroid receptor beta agonist, in patients with non-alcoholic fatty liver disease (NAFLD) and elevated low-density lipoprotein cholesterol (LDL-C).  As previously reported, the study successfully achieved both its primary and secondary endpoints, and demonstrated an encouraging safety and tolerability profile.  Newly presented data provide further detail on the trial endpoints, highlighting the changes to LDL-C, atherogenic proteins, and other liver parameters.  The results were presented Monday, November 12 as part of the Oral Late-Breaker session of The Liver Meeting^® 2018, the annual meeting of the American Association for the Study of Liver Diseases (AASLD), held November 9 – 13 in San Francisco, CA.  

Data presented at The Liver Meeting 2018 include:

Reduction in LDL-C

The study successfully achieved its primary endpoint, with patients receiving VK2809 demonstrating statistically significant reductions in LDL-C compared with placebo following 12 weeks of treatment.

In addition to LDL-C, VK2809-treated patients also demonstrated statistically significant improvements in other lipids, including atherogenic proteins apolipoprotein B and lipoprotein (a).  These improvements suggest potential cardiovascular benefit associated with VK2809 treatment.

Reduction in Liver Fat Content

The study successfully achieved its secondary endpoint, with VK2809-treated patients experiencing statistically significant reductions in liver fat content compared with placebo after 12 weeks of treatment.  As previously reported, up to 91% of VK2809-treated patients demonstrated ≥ 30% reduction in liver fat content at 12 weeks.  Newly reported data from a 'super'-responder analysis demonstrated that 67% of VK2809-treated patients demonstrated ≥ 50% reduction in liver fat content at 12 weeks.  Liver fat content was assessed by magnetic resonance imaging, proton density fat fraction (MRI-PDFF).

Safety and Tolerability

No serious adverse events (SAEs) were reported among patients receiving VK2809 or placebo.  Overall adverse events were evenly distributed across all cohorts, with a slightly greater incidence among patients receiving placebo compared with VK2809-treated patients.  Mean alanine aminotransferase (ALT) levels among patients receiving VK2809 were reduced relative to those of patients receiving placebo at Week 12, and at a Week 16 follow-up visit.  Among patients with elevated ALT at baseline, those receiving VK2809 demonstrated even greater reductions in mean ALT levels relative to placebo at Weeks 12 and 16.  In VK2809-treated patients with elevated baseline ALT (n=13),  levels at Week 16 were significantly reduced from baseline by 20.7 U/L (p=0.02).  By comparison, patients with elevated baseline ALT levels treated with placebo (n=5) experienced an increase from baseline of 11.6 U/L at Week 16.  Mean aspartate aminotransferase (AST) levels among VK2809-treated patients were also reduced relative to placebo at Weeks 12 and 16.

There were no clinically or numerically meaningful differences in direct bilirubin, indirect bilirubin, alkaline phosphatase, or international normalized ration (INR) between patients treated with VK2809 or placebo.  In addition, no changes to the thyroid hormone axis were observed among VK2809-treated patients compared with placebo-treated patients.  There were no changes to cardiovascular toxicity markers such as troponin and NT-proBNP among VK2809-treated patients compared with placebo.  In addition, VK2809 was also shown to be well-tolerated in this study, with no differences in GI-related adverse events compared with placebo.  

"The fact that two-thirds of patients treated with VK2809 achieved at least a 50% reduction in liver fat content is striking, particularly in light of the relatively short duration of treatment evaluated in this trial.  While our research suggests that reducing liver fat by at least 30% increases the likelihood of triggering a potential histologic response in non-alcoholic steatohepatitis (NASH) patients, we would expect that patients who have their liver fat content reduced by more than half may even have a higher likelihood of improvement in liver histology when assessed in a future biopsy-based trial," stated Rohit Loomba, M.D., MHSc, Director, NAFLD Research Center, and Professor of Medicine, University of California at San Diego.  "These robust liver fat content reductions combined with the improvements in levels of LDL-C suggest that VK2809 has a potential for both cardioprotective, as well as improvement in liver histology, in NASH patients in future trials."

"We are very pleased with the safety and efficacy results demonstrated in this trial, which provide us with confidence in VK2809's potential benefit in patients with NAFLD and NASH," stated Brian Lian, Ph.D., chief executive officer of Viking.  "The reductions in liver fat, LDL-C, triglycerides and atherogenic proteins suggest a highly differentiated therapeutic profile, which may lead to improved long-term benefits in NASH patients.  In addition, the liver safety data from Weeks 12 and 16 suggest improvement in liver health extending beyond the study end, which bodes well for longer-term trials s.  Based on these exciting results, we are aggressively moving forward with further clinical studies of VK2809 in NASH, which we expect to initiate in 2019."

Study Design

The Phase 2 study was a randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the efficacy, safety and tolerability of VK2809 in patients with elevated LDL-C and NAFLD.  Patients were randomized to receive placebo, 10 mg VK2809 dosed every other day, or 10 mg VK2809 dosed daily for 12 weeks.  The trial's primary endpoint assessed the effect of VK2809 treatment on LDL-C after 12 weeks compared to placebo.  The secondary endpoint evaluated changes in liver fat content by MRI-PDFF in patients with a valid baseline and post-baseline MRI.  Patients returned for assessment at Week 16, following a four-week off-drug phase. 

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 successfully achieved primary and secondary endpoints in a Phase 2 study for the treatment of patients with elevated LDL-C and non-alcoholic fatty liver disease (NAFLD).  The company is also preparing to evaluate VK2809 in a Phase 1 study for the treatment of patients with GSD Ia.  VK2809 belongs to a family of novel prodrugs, which are cleaved in vivo to release potent thyromimetics.  Selective activation of the TRß receptor in liver tissue is believed to favorably affect cholesterol and lipoprotein levels via multiple mechanisms, including increasing the expression genes associated with lipid metabolism and clearance.  

About Viking Therapeutics, Inc. Viking Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on the development of novel, first-in-class or best-in-class therapies for metabolic and endocrine disorders.  The company'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 small molecule thyroid beta agonist.  In a Phase 2 trial for the treatment of non-alcoholic fatty liver disease and elevated LDL-C, patients who received VK2809 demonstrated statistically significant reductions in LDL-C and liver fat content. VK2809 was shown to be safe and well-tolerated in the study.  The company's second clinical program is VK5211, an orally available, non-steroidal selective androgen receptor modulator.  In a Phase 2 trial in patients recovering from hip fracture, patients who received VK5211 experienced significant improvements in measures of lean body mass compared to patients who received placebo.  The company is also developing VK0612, a first-in-class, orally available drug candidate in Phase 2 development for type 2 diabetes.  Additional programs include novel and selective agonists of the thyroid beta receptor for GSD Ia and X-linked adrenoleukodystrophy, as well as two earlier-stage programs targeting metabolic diseases and anemia.  Viking holds exclusive worldwide rights to a portfolio of five therapeutic programs in clinical trials or preclinical studies, including those noted above, which are based on small molecules licensed from Ligand Pharmaceuticals Incorporated.

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 development activities, timelines and milestones, as well as the company's goals and plans regarding VK2809 and its prospects. 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 VK5211 and VK2809; 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, 2017, 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.