With the FDA due to announce the approval of the first drug for metabolic dysfunction-associated steatohepatitis (MASH), Ionis Pharmaceuticals is raising its hand to showcase a phase 2 asset that has improved symptoms of the liver disease.
ION224 was tested in 160 patients with MASH, previously known as nonalcoholic steatohepatitis (NASH), over 51 weeks, according to a Wednesday press release. The main goal of the trial was liver histological improvement, measured by a standard scoring system for nonalcoholic fatty liver diseases like MASH.
The trial met the goal with both 120-mg and 90-mg doses, showing at least a two-point reduction in the metabolic dysfunction-associated steatotic liver disease (MASLD) disease activity score, which ranks symptoms such as fat buildup in the liver, scarring, inflammation and ballooning. A subgroup analysis also showed significant improvements in patients who have more advanced fibrosis. ION224 also achieved statistically significant MASH resolution without worsening of fibrosis, which was a key secondary endpoint. This was measured by liver biopsy.
The therapy also beat placebo on a measurement of fat buildup, with 44% of patients in the 120-mg group achieving a greater than 50% reduction in buildup, compared to 3% on placebo. And 32% of patients in this high-dose group had a one-stage improvement in liver fibrosis without worsening steatohepatitis as measured by biopsy, compared to just 12.5% who received placebo.
ION224 is a ligand-conjugated antisense therapy that aims to reduce the production of diacylglycerol acyltransferase 2, an enzyme that kicks off the final step in triglyceride synthesis in the liver. Ionis theorizes that reducing the production of the enzyme should decrease triglyceride synthesis and treat MASH.
Ionis believes it has a unique approach to the disease. The University of California, San Diego’s Rohit Loomba, M.D., said the therapy could be complementary to other MASH therapies that are in development. He serves as professor of medicine and chief of the division of gastroenterology and hepatology at the university and is the founding director of the MASLD Research Center there.
And ION224 will have plenty of medicines to pair up with. Madrigal Pharmaceuticals is awaiting a much-anticipated FDA nod for resmetirom, which has an action date of March 14. Elsewhere, Big Pharmas have returned to the space thanks to evidence linking obesity GLP-1 drugs to improvements in the condition. Novo Nordisk just showed that with Wegovy.
Ionis plans to share full results from the phase 2 trial at a future medical meeting.