Viking Therapeutics, Inc. announced positive 52-week histologic data from its Phase 2b VOYAGE study of VK2809, the company's novel liver-selective thyroid hormone receptor beta agonist, in patients with biopsy-confirmed non-alcoholic steatohepatitis (NASH). As previously reported, 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 results announced highlight achievement of secondary endpoints evaluating histologic changes assessed by hepatic biopsy after 52 weeks of treatment with VK2809.

On the secondary endpoint of NASH resolution with no worsening of fibrosis, VK2809-treated patients demonstrated NASH resolution ranging from 63% to 75%, compared with 29% for placebo (p<0.05 for each VK2809 treatment group). Across the combined VK2809 treatment groups, 69% achieved NASH resolution (p<0.0001 vs. placebo).

Resolution of NASH was defined as a non-alcoholic fatty liver disease activity score (NAS) of 0 or 1 for inflammation and 0 for ballooning. On the secondary endpoint evaluating improvement in fibrosis with no worsening of NASH, VK2809-treated patients demonstrated improvement in fibrosis ranging from 44% to 57%, compared with 34% for placebo (p<0.05 for the 5 mg and 10 mg QOD cohorts). Across the combined VK2809 treatment groups, 51% achieved improvement in fibrosis with no worsening of NASH (p=0.03 vs.

placebo). Improvement in fibrosis without worsening of NASH was defined as a =1-stage improvement in fibrosis and no increase in NAS for ballooning, inflammation, or steatosis. On the secondary endpoint evaluating the proportion of patients experiencing both resolution of NASH and improvement in fibrosis, VK2809-treated patients demonstrated improvement ranging from 40% to 50%, compared with 20% for placebo (p<0.05 for the 5 mg and 10 mg QOD cohorts).

Across the combined VK2809 treatment groups, 44% achieved this endpoint (p=0.003 vs. placebo). As reported previously, patients receiving VK2809 demonstrated statistically significant reductions in liver fat at Week 12, which was the primary endpoint in VOYAGE.

Importantly, patients receiving VK2809 continued to demonstrate statistically significant reductions in liver fat content at Week 52, with the mean relative change from baseline ranging from 37% to 55%. The response rate in this study, defined as the proportion of patients experiencing reduction in liver fat =30%, ranged from 64% to 88%, with all treatment arms demonstrating statistically significant improvement compared to placebo. Consistent with prior studies, patients receiving VK2809 demonstrated placebo-adjusted reductions in LDL-C ranging from 20% to 25% (p<0.01 for each arm), as well as reductions in triglycerides and atherogenic proteins such as apolipoprotein B (ApoB), lipoprotein (a) [Lp(a)], and apolipoprotein C-III (ApoC-III), all of which have been correlated with cardiovascular risk.

These results support prior data demonstrating that VK2809 may offer a cardio-protective benefit through its robust reduction in plasma lipids. VK2809 demonstrated encouraging safety and tolerability in this study through 52 weeks of treatment, with minimal differences compared with the previously reported results at 12 weeks. 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. As reported in the topline data release last year, 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, and at the 12-week timepoint in this study, VK2809 demonstrated excellent gastrointestinal (GI) tolerability throughout the 52-week treatment window in this study. Rates of nausea, diarrhea, stool frequency, and vomiting were similar among VK2809-treated patients compared to placebo.

After 52 weeks, plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were reduced in every treatment arm receiving VK2809 compared with patients receiving placebo, though not all treatment arms achieved statistically significant improvement vs. placebo. 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.