A David vs Goliath battle is looming in metabolic dysfunction-associated steatohepatitis (MASH), a disease that was once labeled as a “graveyard” for drug developers but now has two approved treatments and several others, especially incretin-based therapies, in development.
Elsewhere, Roche’s decision to pit its next-generation KRAS G12C inhibitor divarasib against the two approved drugs in the class may have paid off, and Samsung Bioepis’s SB27 has become the first biosimilar to Merck & Co’s Keytruda (pembrolizumab) to report global Phase III data.
Let’s dig in.
A David Vs Goliath Battle
Maryland-based Altimmune is hoping that a clean safety and tolerability profile of its Phase III-ready dual GLP-1/glucagon (GCG) receptor agonist can give it an edge in MASH against three established and deeper-pocketed biopharma firms – Eli Lilly, Merck & Co. and Boehringer Ingelheim.
Altimmune is preparing to initiate a Phase III study of pemvidutide in MASH later this year, after the drug showed placebo-like safety and tolerability in the Phase IIb IMPACT study, while having demonstrated the ability to clear MASH and reduce weight. But the drug’s prospects have been viewed as mixed because 24-week data from IMPACT missed the co-primary endpoint of at least one stage of fibrosis score improvement without worsening of MASH.
MASH, previously known as non-alcoholic steatohepatitis (NASH), has always been a desirable target for pharmaceutical firms given the large prevalent population and a rise in liver transplants due to the disease. More recently, incretin-based therapies such as GLP-1 receptor agonists are being trialed for the disease, with Novo Nordisk’s GLP-1 analog Wegovy (semaglutide) already approved for the condition, along with Madrigal Pharmaceuticals’ Rezdiffra (resmetirom), a THRβ agonist.
Altimmune chief medical officer Christophe Arbet-Engels told Scrip that the company intends to begin the Phase III PERFORMA study of pemvidutide in MASH, before the end of 2026 with a plan to study two- and three-step dose-titration schemes in an effort to best balance safety and efficacy.