VKTX Viking Therapeutics Inc

SAN DIEGO, April 11, 2019 /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 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) at the International Liver Congress^™ 2019.  The study results were presented in the late-breaker poster session of the annual meeting of the European Association for the Study of the Liver (EASL), being held April 10-14 in Vienna, Austria.

Highlights from the late-breaker poster include newly reported data demonstrating that all patients who received 5 mg of VK2809 dosed daily were considered responders, as defined by a relative reduction in liver fat of ≥ 30% at Week 12.  Patients in the VK2809 5 mg cohort also experienced a statistically significant median relative reduction in liver fat content of 53.8%.  Consistent with the observations from the 10 mg cohorts in this study, VK2809 was shown to be safe and well tolerated when dosed at 5 mg daily, with no serious adverse events reported.  Overall, a greater proportion of VK2809-treated patients completed the study compared with patients randomized to placebo.

Data presented at The International Liver Congress 2019 include:

Reduction in LDL-C

The study successfully achieved its primary endpoint, with patients receiving VK2809 demonstrating statistically significant reductions in LDL-C following 12 weeks of treatment.  In addition to LDL-C, VK2809-treated patients also demonstrated statistically significant improvements in other lipids, including triglycerides and the 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.  Newly reported data demonstrated that 100% of patients receiving 5 mg of VK2809 dosed daily were considered responders, experiencing ≥ 30% relative reduction from baseline in liver fat content at Week 12.  With new data from the study's 5 mg cohort, the overall responder rate for VK2809-treated patients increased to 88%, compared to approximately 17% for patients randomized to placebo.  Furthermore, the study's 'super'-responder rate for VK2809-treated patients increased to 70% when data from the 5 mg cohort are incorporated.  'Super'-responders are those patients who demonstrated ≥ 50% reduction in liver fat content at 12 weeks.  Overall, the results from the 5 mg daily dosing cohort are comparable to previously reported results for study patients receiving 10 mg VK2809 dosed every other day or 10 mg VK2809 dosed daily for 12 weeks.  Liver fat content was assessed by magnetic resonance imaging, proton density fat fraction (MRI-PDFF).

Safety and Tolerability

VK2809 was shown to be safe and well tolerated at all doses evaluated in this study.  No serious adverse events (SAEs) were reported among patients receiving either VK2809 or placebo.  The incidence of overall adverse events (AEs) and treatment-emergent adverse events (TEAEs) were relatively evenly distributed between patients receiving VK2809 compared with patients receiving placebo.  A greater proportion of VK2809-treated patients completed the study compared with patients receiving placebo and the rate of study discontinuation due to an adverse event was similar for patients receiving either placebo or VK2809.

Mean alanine aminotransferase (ALT) levels among patients receiving VK2809 were reduced relative to those of patients receiving placebo at Week 12.  Among patients with elevated ALT at baseline, those receiving VK2809 demonstrated even greater reductions in mean ALT levels relative to placebo at Weeks 12.  Mean aspartate aminotransferase (AST) levels among VK2809-treated patients were also reduced relative to placebo at Weeks 12.  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.  

VK2809 demonstrated encouraging cardiovascular safety in this study.  The proportion of VK2809-treated patients reporting a CV-related AE was comparable to, though numerically lower than, the proportion of placebo-treated patients reporting a CV-related AE.  No changes to cardiovascular toxicity markers such as troponin, CK-MB, or NT-proBNP were observed among VK2809-treated patients compared with placebo.  Additionally, no clinically meaningful changes to the thyroid hormone axis were observed among VK2809-treated patients compared with placebo-treated patients.  VK2809 was also shown to be well-tolerated in this study, with no differences in gastrointestinal-related adverse events compared with placebo.  

Based on these study results, Viking is preparing to initiate a Phase 2b study of VK2809 in patients with biopsy-confirmed non-alcoholic steatohepatitis (NASH), which is anticipated to begin in the second half of 2019.

"The liver fat reductions produced by low-dose VK2809 are impressive and may suggest improvement in histology in longer-term biopsy-based studies.  Our research suggests that reducing liver fat by 30% or more increases the likelihood of a potential histologic response in NASH patients.  Since more than two-thirds of patients receiving VK2809 demonstrated at least a 50% reduction in liver fat we would expect a potentially higher likelihood of improved liver histology," stated Rohit Loomba, M.D., MHSc, Director, NAFLD Research Center, and Professor of Medicine, University of California at San Diego. "These robust improvements in liver fat content, combined with reductions in plasma lipids such as LDL-C suggest a potential cardioprotective benefit in these patients, which would represent a promising and novel profile."

"We are gratified that VK2809's robust efficacy is maintained at doses as low as 5 mg daily.  The results observed at 5 mg are similar to those obtained at higher doses and support our enthusiasm for VK2809's promise as a potential therapy for patients with NASH.  The totality of data suggests a differentiated therapeutic profile, with the potential to improve liver health and provide global benefits on systemic lipids such as LDL-C and atherogenic proteins," stated Brian Lian, Ph.D., chief executive officer of Viking.  "We are also encouraged by VK2809's preliminary safety and tolerability profile, and in particular that no SAEs have been observed in any study to date.  In this Phase 2 study, the number of patients completing treatment, reporting treatment-emergent AEs, and discontinuing due to AEs all appear well-balanced between treatment and placebo cohorts.  Importantly, liver and cardiovascular safety are promising, with mean ALT and AST levels reduced relative to placebo and no evidence of changes observed to vital signs or markers of cardiovascular safety.  We look forward to initiating our planned Phase 2b study in patients with biopsy-confirmed NASH later this year."

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, 5 mg VK2809 dosed daily, 10 mg VK2809 dosed every other day, or 10 mg VK2809 dosed daily for 12 weeks.  Completion of enrollment of patients in the 5 mg cohort was deferred until enrollment was complete in the 10 mg QD and 10 mg QOD arms.  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.    

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).  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 is a clinical-stage biopharmaceutical company focused on the development of novel, orally available, first-in-class or best-in-class therapies for the treatment of metabolic and endocrine disorders.  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, including non-alcoholic steatohepatitis (NASH).  In a Phase 2 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 VK0214, a novel, orally available, small molecule selective thyroid hormone receptor beta agonist for the treatment of X-linked adrenoleukodystrophy (X-ALD).

Viking's other programs include 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 with patients who received placebo.  Other programs also include VK0612, a first-in-class, orally available drug candidate in Phase 2 development for the treatment of type 2 diabetes as well as two earlier-stage programs targeting metabolic diseases and anemia.  The company holds exclusive worldwide rights to a portfolio of five therapeutic programs, 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, 2018, 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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