Non-alcoholic steatohepatitis, or NASH, remains a disease with no approved therapeutics. And it’s been a tough area for drug development, with numerous Phase 2b and Phase 3 failures in the last few years. As a result, the landscape of active development projects has changed quite a bit from the time our review on NASH was published in 2019 – which means that it’s time for an update!
Ongoing pivotal Phase 3 studies
As of today, there are four Phase 3 studies ongoing which, if meeting their primary endpoint, could lead to the first approval of a NASH drug:
- A study with resmetirom (MAESTRO-NASH), a liver-directed thyroid hormone receptor-beta agonist, is due to read out later this year. There has been a previous successful Phase 3 study in NAFLD, showing that the drug is capable of reducing liver fat, and, with this, many of the detrimental effects this brings.
- NATiV3 is a study evaluating the efficacy and safety of lanifibranor, a pan-PPAR activator, in NASH, and is expected to have results in 2024.
- The ARMOR study is evaluating the synthetic fatty acid conjugate aramchol, which also promises to beneficially influence fat metabolism in the liver. This study is planned to reach its primary completion date at the end of 2024.
- Finally, the GLP-1 mimetic semaglutide is also being evaluated in a Phase 3 study. While the effects of this drug on metabolism in general, and its safety profile, are well established based on its approval as an antidiabetic, data on its efficacy in NASH is only expected in 2028.
Populations and Endpoints
While all the above studies are including patients with NASH, there are subtle differences in the patient selection criteria as well as in the primary endpoint. This is a development reflecting an increased understanding of the disease processes, and how the mode of action of a specific drug can interfere therewith – something we as well have suggested as a principle for rational R&D projects in this area.
Enabling therapies for patients
While the situation is not quite comparable with the head-to-head Phase 3 race of elafibranor and obeticholic acid that we witnessed just a few years ago, it’s certainly good to see compounds successfully making their way to pivotal development studies.