79% of Patients Achieve Normal Liver Fat at Week 24 with CIDEBsiRNA

79% of Patients Achieve Normal Liver Fat at Week 24 with CIDEBsiRNA

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Following a single subcutaneous dose of Regeneron Pharmaceuticals, Inc.’s investigational RNA interference therapy CIDEBsiRNA, a substantial proportion of trial participants with metabolic dysfunction-associated steatotic liver disease achieved normal liver fat levels by week 12.

Metabolic dysfunction-associated steatotic liver disease affects approximately 33 percent of adults worldwide, yet effective treatment options remain limited for patients who develop the more severe form known as metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatohepatitis is characterized by liver inflammation, fibrosis, and an increased risk of cirrhosis and related complications. The randomized, double-blind, placebo-controlled study enrolled 40 participants with metabolic dysfunction-associated steatotic liver disease at two United Kingdom clinical research centers, including Richmond Pharmacology. Thirty participants received a single subcutaneous dose of CIDEBsiRNA ranging from 15 milligrams to 600 milligrams, while the remaining participants received a placebo.

By week 12, mean liver fat levels across all four CIDEBsiRNA dose groups fell to or below 5 percent, which is the upper limit of normal as measured by magnetic resonance imaging-proton density fat fraction. At that 12-week mark, 72 percent of treated participants with available measurements achieved normal liver fat levels. That figure increased to 79 percent at week 24, compared with none in the placebo group.

At week 24, 97 percent of treated participants with available measurements reduced liver fat by more than 30 percent, a threshold previously associated with histological improvement in metabolic dysfunction-associated steatohepatitis. Mean serum alanine aminotransferase, a marker of liver injury, decreased by 32 percent at week 12 across the treatment groups, compared with a 5 percent increase in the placebo group.

Those reductions in liver fat and alanine aminotransferase were sustained through week 36 following a single dose, and the therapy was generally well-tolerated with adverse event rates similar between treatment and placebo groups.

The Regeneron Genetics Center discovered CIDEB as a potential therapeutic target through large-scale human genetic analyses that revealed individuals carrying rare loss-of-function variants in the CIDEB gene had lower liver fat levels and a reduced risk of liver disease.

CIDEBsiRNA uses RNA interference to reduce CIDEB protein production in the liver without altering DNA. Since 2014, Richmond Pharmacology has contributed to clinical investigations of RNA interference treatments, which spans administering initial doses to participants for two drugs that later gained regulatory clearance.

“Despite recent advances in the treatment of steatotic liver disease, a substantial unmet need remains for therapies capable of delivering meaningful and durable improvements in liver health,” said Dr. Jörg Täubel, who serves as the study’s Principal Investigator for Richmond Pharmacology, holds the roles of Co-Founder and Executive Chairman at the same organization, and acts as a Visiting Professor at King’s College London, an Honorary Senior Research Fellow at St. George’s University in London and President of the Association for Applied Human Pharmacology (AGAH), Germany.

Richmond Pharmacology said that its involvement in the study reflects the specialist expertise required to translate innovative therapeutic approaches into early clinical development. The findings provide early clinical evidence of the biological activity of CIDEBsiRNA, and the clinical development program is continuing in metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis, including studies involving participants with biopsy-confirmed disease.

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