Icosabutate rapidly reduces biomarkers of liver injury in NASH
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Two doses of icosabutate were well tolerated and safe in patients with nonalcoholic steatohepatitis.
During the Digital NAFLD Summit 2021, Stephen Harrison, MD, chief medical officer at Northsea Therapeutics, icosabutate’s manufacturer, presented the interim, 16-week results of the ICONA trial, an going 52-week, phase 2b study of 264 patients with NASH.
“NASH with fibrosis represents a huge area of unmet need. The positive interim, non-invasive testing data presented, along with the improved metabolic profile, suggest that icosabutate is having a positive impact on both general metabolic health as well as liver health in a short time,” Harrison, professor at Oxford University, told Healio Gastroenterology. "This is really encouraging for the continuation of the study as we move toward repeat liver biopsy at the end of 1 year.”
Harrison and colleagues randomly assigned 90 patients with NASH to icosabutate 300 mg or 600 mg or placebo. Patients received treatment through 16 weeks. During this time, investigators assessed biomarkers of liver injury, inflammation, fibrogenesis, glycemic control and lipid metabolism. At screening and week 16, MRI-proton density fat fraction was used to measure liver fat content.
Results showed ALT, AST, GGT and ALP had rapid, sustained and significant dose-dependent decreases. These levels were predictive of histologic improvement. Harrison and colleagues said both icosabutate doses demonstrated significant reductions in PRO-C3 and Enhanced Liver Fibrosis score, which supports an impact on fibrogenesis.
“All liver chemistry tests measured were significantly reduced with [icosabutate] 600 mg at 16 weeks,” Harrison said during his presentation.
With the 600 mg dose, high sensitivity C-reactive protein was significantly reduced by 52%, and improvements in glycemic control and key atherogenic lipoproteins were also observed. No changes were observed in weight or BMI, which may mean a treatment effect independent of weight loss. With both doses of icosabutate, liver fat content was unchanged and consistent with icosabutate mechanism of action.
“There is reduction in LDL cholesterol as well as [apolipoprotein B-100 (APO B)] and lipoproteins; although not reaching statistical significance at this interim time point,” Harrison said during the presentation. “[Icosabutate] is well tolerated and comparable to placebo except for some mild nausea that was dose response related but did not result in drug discontinuation. There was no significant change in body weight, there was no confirmed drug-induced liver injury, cardiovascular events or changed in glycemic control that resulted in a worsening.”
He said the independent, unblinded data and safety monitoring board review did not raise any safety or tolerability signals.
“The pleiotropic effects of icosabutate targets multiple key drivers of NASH and the positive movement in relevant biomarkers such as ALT, GGT, PRO-C3 and hsCRP support its robust anti-inflammatory and antifibrogenic effects” Stephen Rossi PharmD, chief development officer at Northsea Therapeutics, told Healio Gastroenterology. “We look forward to the completion of the 52-week biopsies and charting a path forward for these patients with high medical need and no approved treatments.”
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Harrison S, et al. Abstract: OS-265. Presented at: Digital NAFLD Summit 2021; Sept. 16-17, 2021 (virtual meeting).
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