Viking Therapeutics’ lead lipid disorder asset met its primary and secondary endpoints in a midstage trial, dropping cholesterol and liver fat levels in patients with nonalcoholic fatty liver disease (NAFLD). The topline data have been submitted for presentation at this year’s meeting of the American Association for the Study of Liver Diseases.
The candidate, known as VK2809, is a thyroid receptor beta agonist that targets the liver and is being developed for lipid disorders such as hypercholesterolemia in addition to NAFLD. Because the drug selectively activates thyroid receptor beta in liver tissue, the company hopes it will avoid side effects—such as quickened breathing and an enlarged heart—that can come with activation of another receptor, thyroid receptor alpha.
Patients in the phase 2 study were randomized to receive placebo or a 10-mg dose of VK2809 either every day or every other day. After 12 weeks of treatment, patients receiving VK2809 had reductions of 20% or more in LDL cholesterol compared to patients on placebo. Only 18% of placebo patients posted a 30% or greater drop in liver fat, while 91% of those receiving daily doses of VK2809 and 77% of those dosed with the drug every other day had a 30% or greater decrease in liver fat.
Instead of biopsy, the study used magnetic resonance imaging, proton density fat fraction (MRI-PDFF) as a noninvasive quantitative biomarker of changes in liver fat content.
“Previous studies by our group have shown that a 30% or greater reduction in MRI-PDFF is associated with higher odds of histologic response in NASH, [a type of NAFLD],” said Rohit Loomba, M.D., director of the NAFLD Research Center and a professor of medicine at the University of California, San Diego. “The quantum of liver fat reduction along with LDL-lowering properties of VK2809 are potentially likely to be beneficial in patients with nonalcoholic steatohepatitis (NASH) who have a significant risk of not only liver fibrosis progression but also cardiovascular disease.”
No serious adverse events were reported.
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"VK2809's effect on liver fat at 12 weeks appears to exceed all other oral agents currently in development for NASH, supporting our view that VK2809 has a best-in-class profile,” said Viking CEO Brian Lian. “[The] improvement in lipid parameters observed in this study suggests potential benefits in cardiovascular health, an important consideration in this population. We look forward to pursuing further development of VK2809 in NASH."
Though the trial was relatively small, Jefferies analysts called the topline results promising.
Viking’s data come seven months after Madrigal Pharma’s lead drug, another liver-directed thyroid hormone receptor beta agonist, met its cholesterol-lowering endpoint in heterozygous familial hypercholesterolemia. The inherited cholesterol disorder is its second target indication, after NASH.
"VKTX looks quite active and efficacious that is similar (or perhaps even better) on key liver endpoints such as MRI-PDFF fat reduction than direct competitor MDGL (both have similar mechanism of liver-selective THR-beta agonist)," the analysts wrote. While Madrigal's trial involved many more patients, had a 24-week MRI-PDFF endpoint and a 36-week biopsy endpoint, the two studies are still not easily comparable as Viking's drug was studied in NAFLD patients, while Madrigal's was tested in NASH patients.