VIDEO: TERN-501 ‘could be a best-in-class molecule’ alone, as combination therapy for MASH

Key takeaways:

• TERN-501 significantly improved liver fat content and fibro-inflammation at 12 weeks in patients with presumed MASH.
• Low rates of GI adverse events and no cardiovascular adverse events were reported.

BOSTON — Treatment with TERN-501, a selective thyroid hormone receptor beta agonist, reduced liver fat content and fibro-inflammation among patients with presumed metabolic dysfunction-associated steatohepatitis, late-breaking data showed.

“The main purpose of the study was to compare three different doses of TERN-501, a highly selective and differentiated THR beta agonist, to placebo,” Erin Quirk, MD, president and head of research and development at Terns Pharmaceuticals, told Healio. “The primary endpoint was the relative change in liver fat content from baseline to week 12.

“We also included some combination arms for TERN-501 and that’s what makes this such a groundbreaking study: It’s the first time a THR beta has been combined with another experimental mechanism for the treatment of MASH,” Quirk added.

According to research presented at The Liver Meeting, 162 patients (mean age, 53 years; 55% women; BMI 38 kg/m2) with presumed MASH were randomized to one of seven treatments: once-daily TERN-501 (1 mg, 3 mg or 6 mg); TERN-101, a nonsteroidal farnesoid X receptor agonist (10 mg); TERN-501 (3 mg or 6 mg) combined with TERN-101 (10 mg); or placebo. The primary endpoint was the relative change in liver fat measured by MRI-proton density fat fraction (PDFF) at 12 weeks.

According to results, mean baseline liver fat content was 18% and fibro-inflammation, measured via corrected T1, was 936 ms. Patients receiving TERN-501 monotherapy (6 mg) had “significant reductions” in liver fat as early as week 6, with mean relative reductions of 27% (3 mg) and 45% (6 mg) vs. 4% in the placebo group at week 12.

In addition, a higher percentage of patients achieved at least a 30% reduction in MRI-PDFF in the TERN-501 groups, with the 6 mg group achieving at least a 50% reduction at week 12. Participants in the TERN-501 6 mg group also experienced “significant, rapid” cT1 decrease, with a significantly higher percentage of patients in this group achieving at least 80 ms reduction.

“When we combine TERN-501 with TERN-101 in the combination arms, the efficacy was generally maintained and modestly improved without additional safety findings,” Quirk said. “This is important because it demonstrates the combinability of TERN-501.”

Further, TERN-501 was well-tolerated, with low rates of gastrointestinal adverse events and no treatment-related cardiovascular or serious adverse events.

“As we look to the future, we think that MASH treatment will involve treatment with a combination of different therapies for MASH, and we think that TERN-501 has the potential to be an anchor drug in a combination regimen as it is showing potential best in class THR beta profile,” Quirk told Healio. “Collectively, we think these data indicate that TERN-501 could be that best-in-class molecule to be administered in patients as a monotherapy or in combination with other mechanisms of action for MASH.”

Reference:

• Terns Pharmaceuticals presents late-breaking data from phase 2a DUET trial of THR-B agonist TERN 501 in NASH at The Liver Meeting 2023. https://ir.ternspharma.com/news-releases/news-release-details/terns-pharmaceuticals-presents-late-breaking-data-phase-2a-duet. Published Nov. 13, 2023. Accessed Nov. 15, 2023.