Viking Strengthens NASH Candidate with Histological Data

Viking Therapeutics announced additional findings from its Phase IIb VOYAGE study on Tuesday, revealing that its experimental thyroid hormone beta receptor agonist, VK2809, significantly improved histologic outcomes in patients with nonalcoholic steatohepatitis (NASH).

The data, collected over a 52-week period, indicated that between 63% and 75% of patients administered VK2809 achieved resolution of NASH without the worsening of fibrosis. In sharp contrast, only 29% of patients in the placebo group reached this endpoint, with the statistical analysis favoring the investigational treatment.

Further, the study showed notable improvements in fibrosis. Specifically, 51.9% and 56.8% of patients receiving 5 mg and 10 mg doses of VK2809 every other day, respectively, experienced at least a one-stage improvement in fibrosis. This compares to just 34.1% in the placebo group, with the differences being statistically significant, marked by p-values of 0.0304 and 0.0497.

William Blair analyst Andy Hsieh referred to the fibrosis improvement as the "most impressive upside surprise" from the new data, despite the study not being fully powered to evaluate this endpoint. Hsieh emphasized that fibrosis is the best indicator for long-term NASH outcomes such as disease progression and mortality. He believes that demonstrating statistically significant improvement in fibrosis sets VK2809 apart from other treatments in the NASH space, potentially establishing it as the most potent oral treatment available.

VK2809's positive outcomes on fibrosis could position it favorably against Madrigal’s Rezdiffra (resmetirom), which was the first FDA-approved NASH treatment in March 2024. Hsieh highlighted that Rezdiffra did not achieve fibrosis improvement in Madrigal’s Phase II trial.

Despite these promising results, Viking’s shares fell by 15% following the announcement. Hsieh attributed this decline to the lack of immediate catalysts and the substantial investment of capital and time required for a large-scale global Phase III program.

During an investor call, Viking CEO Brian Lian mentioned that the company plans to meet with the FDA later this year to discuss potential next steps for VK2809.

VK2809 is designed as an oral drug with high selectivity for liver tissue, activating the thyroid hormone beta receptor. This mechanism enhances the expression of genes involved in lipid metabolism and clearance, thereby improving cholesterol and lipoprotein levels.

The recent data drop builds on findings from May 2023, which showed that VK2809 met the primary endpoint of the VOYAGE trial by significantly reducing liver fat.

Hsieh also pointed to stiff competition from other pipeline candidates, such as Eli Lilly’s tirzepatide, which had shown impressive results in resolving NASH without worsening fibrosis in 74% of patients in its Phase II study, versus 13% in the placebo group. Furthermore, Novo Nordisk’s semaglutide has been assessed for NASH, showing disease resolution without worsening of fibrosis in up to 59% of patients.

The market's reaction to Viking’s data suggests that investors are cautious about the long path ahead and the competitive landscape in the NASH treatment arena.