Lilly’s tirzepatide proves its MASH mettle in mid-stage update at EASL
05 Jun 2024
Clinical ResultPhase 2Drug Approval
After securing near-celebrity status for tirzepatide as a diabetes and obesity treatment, Eli Lilly has been exploring the dual GLP-1/GIP agonistGLP-1/GIP agonist’s potential in metabolic dysfunction-associated steatohepatitis (MASH) – and new histological data seem to support that venture. A late-breaker abstract published Wednesday ahead of the European Association for the Study of the Liver (EASL) congress details the magnitude by which tirezpatide improved fibrosis in the Phase II SYNERGY-NASH trial.
The pharma’s leadership had previously teased the secondary endpoint results as “clinically meaningful” in February. At the time, Lilly had disclosed 52-week data showing that the 5mg, 10mg, and 15mg doses of tirzepatide all met the primary endpoint of MASH resolution with no worsening of fibrosis, with an improvement rate of 73.9% for participants who received the highest dose compared to 12.6% for those on placebo.
The EASL abstract revealed that on the secondary endpoint, tirzepatide led to at least a one-stage reduction in fibrosis with no worsening of MASH in 51% of patients who received the highest dose, 51.3% of those taking the medium dose, and 54.9% for the the lowest dose, a statistically significant improvement over the placebo arm, which had a rate of 29.7%.
Tirzepatide’s placebo-adjusted improvement range of 21.3% to 25.2% was in-line with data shared earlier this week by Viking Therapeutics, whose THR-β selective agonist VK2809 achieved a 22.7% benefit versus placebo at a 10mg dose given every other day.
In contrast, the sole marketed drug for MASH, Madrigal Pharmaceuticals’ Rezdiffra (resmetirom) – which just won FDA approval in March – saw a roughly 12% placebo-adjusted fibrosis improvement of at least one stage with no worsening of MASH in its pivotal study.
Biomarker improvements
The data also demonstrated that 71.7% to 78.3% of all patients who received tirzepatide achieved a reduction in nonalcoholic fatty liver disease activity score (NAS) by two points or more, compared with 36.7% for placebo.
Additionally, Lilly found that patients experienced a decrease in liver enzymes and liver fat, as well as a significant improvement in key imaging biomarkers of liver inflammation and fibrosis. The company noted that those who received tirzepatide had mostly mild-to-moderate adverse events that were mainly gastrointestinal in nature. Plus, patients in the experimental arm had a body weight reduction of up to 17.3%.
While the data appear impressive, the development of tirzepatide for MASH may be tricky as Lilly deals with overwhelming demand and limited supply of the GLP-1/GIP agonistGLP-1/GIP agonist. Lilly recently earmarked $9 billion to boost production capacity of the drug at its manufacturing site in Lebanon, Indiana as it deals with bottlenecks linked to the plastic pens used to inject tirzepatide.
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