The Liver Meeting
The Liver Meeting
November 13, 2018
4 min read

Thyroid receptor agonist improves fatty liver in 91% of patients

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Rohit Loomba, MD
Rohit Loomba

SAN FRANCISCO — VK2809, a thyroid receptor beta agonist, showed an impact on nearly all treated patients as measured by magnetic resonance imaging-proton density fat fraction, according to late breaking data presented at The Liver Meeting 2018.

“Up to 91% of individuals had a significant improvement in liver fat by the criteria of 30% or more in MRI-PDFF reduction,” Rohit Loomba, MD, of the University of California San Diego, said during his Late Breaker presentation. “Planning for subsequent study with biopsy-confirmed NASH is underway.”

In this phase 2, double-blind study, Loomba and colleagues randomly assigned patients with NAFLD and hypercholesteremia to either placebo (n = 15), 10 mg VK2809 (Viking Therapeutics) every other day (n = 16) or 10 mg daily (n = 16). Treatment occurred over 12 weeks with 4 weeks follow-up. The primary endpoint in this study was change in LDL vs. placebo with a secondary endpoint in change in liver fat as measured by MRI-PDFF. Exploratory endpoints were changes in atherogenic lipoproteins, Loomba said.


At 12 weeks, Loomba showed that there was LDL reduction seen in the treatment groups vs. placebo. Placebo LDL increased by 0.53 mg/dL; the every-other-day group decreased by 32.3 mg/dL (–23.6%; P = .0121) and the daily group decreased by 25.2 mg/dL (–20.2%; P = .0269). Combined, the treatment groups showed a 21.8% decline in LDL (P = .0061).

“This is one of the most significant reductions that we have noted in a 12-week trial with an oral therapy,” Loomba said.

Using MRI-PDFF, Loomba showed relative reductions in liver fat with VK2809 treatment. The placebo group had 8.9% reduction in liver fat while the every-other-day treatment group showed a 56.5% reduction in liver fat (P = .014). The daily treatment group showed a 59.7% reduction (P = .0003) and, combined, the treatment groups showed a 58.1% reduction in liver fat (P = .0002). These equate to 72% relative reduction for every-other-day dosing and 76% relative reduction for daily dosing, Loomba said.

At the absolute reduction level, the placebo group showed an absolute reduction of 0.9% while the every-other-day group showed 8.9% absolute reduction (P = .011). The daily group showed an absolute reduction of 10.6% (P = .0025) and, combined, they showed a 9.7% absolute reduction (P = .0019).

Responders, ‘Super responders’

“In previous studies, we have shown that a 30% decrease in MRI-PDFF relative to baseline in a 24-week trial if you were to have histology may have a 2-point improvement in NAFLD activity score,” Loomba said.


Loomba defined response as 30% or more decrease in liver fat by week 12. With this definition, 18.2% of the placebo group responded. In contrast, 76.9% of the every-other-day group responded (P = .012), 90.9% of the daily treatment group (P = .0019) and, combined, 83.3% of those treated were classified as responders (P = .0011).

“Super responders” were then defined as those who had a 50% or more reduction in liver fat at 12 weeks, Loomba said. In the placebo group, 18.2% could be classified as super responders. In the every-other-day group, 61.5% fell into this category (P = .047) and 72.7% of those in the daily treatment group did as well (P = .03). Together, the treatment groups saw 66.7% of participants classified as “super responders” (P = .021).

Other parameters

In looking at the atherogenic protein levels at 12 weeks, Loomba showed reductions in both lipoprotein(a) and apolipoprotein. In lipoprotein(a), the placebo group increased by 4.7% while the every-other-day group decreased by 36.8%, the daily group by 24.6% (P = .049) and, combined, by 30.4% (P = .039). In apolipoprotein, the placebo group increased by 0.4% while the every-other-day group decreased by 23.7% (P = .0021), the daily group by 17.4% (P = .02) and, combined, by 20.4% (P = .021).

These results suggest “potentially some cardiovascular benefit if continued,” Loomba said.

VK2809 was safe and well tolerated, Loomba reported.

Most liver parameters outside of MRI-PDFF measurements remained stable, he said, though in patients with baseline ALT greater than the upper limit of normal, VK2809 treatment produced a lowering of ALT and AST, though only the week 16 ALT measurement was of any significance.

Loomba noted that with a thyroid receptor agonist, there is an initial spike in ALT due to a rapid influx of lipids when treatment begins, but it is followed by a quick and effective decline.

Patients with elevated baseline ALT showed the greatest disease improvement and the progression suggested continued improved benefit in those patients with greater disease activity, Loomba said.

“VK2809 produced robust reduction in liver fat as measured by MRI-PDFF ... in patients with NAFLD and hyperlipidemia after 12 weeks of oral dosing,” he said. – by Katrina Altersitz


Loomba R, et al. Abstract LB-04. Presented at: The Liver Meeting 2018; Nov. 9-13, 2018; San Francisco.

Disclosure: Loomba reports receiving grant or research support from Adheron, Allergan, Arisaph, BMS, Eli Lilly, Galectin, Galmed, GE, Genfit, Gilead, Immuron, Intercept, Kinemed, Merck, NGM, NuSirt, Octeta, Inc., Promedior, Shire and Siemens; participating in advisory committees or review panels for Arrowhead Research, Conatus, Gilead, Galmed, Gemphire, Intercept, Median Technologies, Octeta and Second Genome; holding patents for LipoNexus Inc.; consulting for Allergan, Arrowhead Research, Bird Rock Bio, BMS, Boehringer Ingelheim, Celgene, Cirius, CohBar, Conatus, Cymabay, Eli Lilly, Gemphire, Gilead, Glympse bio, GNI, GRI, Intercept, Ionis, Janssen Inc., Metacrine, NGM, Novo Nordisk, Novo Nordisk, Pfizer and Second Genome Technologies; and holding shares of stock in Viking Therapeutics.