Q&A: TERN-101 may be tolerable in patients with NASH
Terns Pharmaceuticals Inc. announced positive topline results from the phase 2a Lift study of TERN-101 for the treatment of patients with nonalcoholic steatohepatitis.
According to a press release, TERN-101 is a liver-distributed farnesoid X receptor (FXR) agonist. In the LIFT study, researchers assessed the safety, tolerability, efficacy and pharmacokinetics of TERN-101 tablets at doses of 5 mg, 10 mg and 15 mg in 100 adult patients with presumed non-cirrhotic NASH.
The primary objective was the evaluation of safety and tolerability over 12 weeks of treatment plus 4 weeks after treatment. Other endpoints included percent change from baseline in ALT levels, plasma pharmacokinetics of TERN-101, changes in liver fibro-inflammation measured by MRI corrected T1 (cT1), liver fat content by MRI proton density fat fraction (MRI-PDFF), pharmacodynamic parameters, and serum NASH biomarkers.
Healio Gastroenterology spoke with Rohit Loomba, MD, MHSC, director of hepatology and director, NAFLD Research Center, University of California, San Diego, about the phase 2a trial take-aways and the next step in research on TERN-101.
Healio: What was the purpose and design of this study?
Loomba: It was a randomized, placebo-controlled, phase 2A trial to look at the safety, tolerability and initial efficacy of TERN-101 — an FXR agonist — to assess in patients with high-risk nonalcoholic fatty liver disease. We looked at safety and tolerability in terms of LDL cholesterol, as well as pruritus. We also looked at different doses and the response to alanine aminotransferase, aspartate aminotransferase as well as liver fat by MRI-PDFF.
Healio: What were some of the key takeaways from this study?
Loomba: We were able to see that the drug was active, relative to placebo, we saw reductions in liver fat. We also noticed improvements in serum ALT and that there were no grade 4 or higher adverse events in the trial, and none of the adverse events led to discontinuation of the drug. This is important because as you know FXR agonist are associated with pruritus leading to drug discontinuation. We also did not notice significant increases related to LDL cholesterol as we have seen in other trials with FXR agonists; they were there but it wasn't to the degree that we've noticed with some of the other drugs. Although these are early results and there’s no head to head comparison; these findings are encouraging. Overall, it appears to be tolerable. It could have a role developing some of the other treatments such as our hormone beta receptor agonist, as well as other drugs that target patients with NASH with a different mechanism of action. It will be a good approach for them to use as a combination therapy with a thyroid hormone receptor Beta agonist. That’s the kind of approach that they are thinking about in future.
Healio: What is the next step in research for this?
Loomba: The next step would be to design a larger, Phase 2b trial, to assess the efficacy relative to placebo over a longer duration of time among patients with biopsy-proven NASH with stage 1-3 fibrosis. In the next trial, they will look at changes in liver histology as monotherapy relative to placebo, as well as, combination therapy and to look at histologic responses in terms of improvement in fibrosis and NASH resolution. We saw some of the noninvasive biomarkers that show response, but the next step would be to look at histologic responses in patients with biopsy-proven NASH and NASH-related fibrosis.