Eliminating an itchy side effect

By visualizing how analogs of bile acids bind to mas-related G-protein coupled receptor member X4 (MRGPRX4), scientists think they may have discovered the molecular mechanism that causes itchy side effects in people who take the drug obeticholic acid. The researchers propose that a small molecular change could eliminate the itch ( Cell 2024, DOI: 10.1016/j.cell.2024.10.001 ). Obeticholic acid, which is marketed as Ocaliva as a treatment for a type of liver disease known as primary biliary cholangitis , has come under scrutiny recently. Although the US Food and Drug Administration approved obeticholic acid in 2016 under its accelerated pathway, the agency restricted the drug’s use in 2021, and an FDA advisory committee voted not to extend full approval to the drug in September 2024. The committee found that data don’t demonstrate clinical benefit, and the drug doesn’t have a favorable risk-benefit profile. The FDA doesn’t have to follow the advisory