CAMBRIDGE, MA–Alnylam Pharmaceuticals and Regeneron Pharmaceuticals have reported encouraging early clinical results for an experimental RNA interference treatment that reduced liver fat by as much as 80% following a single injection in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).
The findings from an ongoing Phase 1/2 clinical trial showed that a single subcutaneous dose of CIDEBsiRNA, previously known as ALN-CIDEB, produced rapid and sustained reductions in liver fat, with effects lasting through 36 weeks.
The results were published in The New England Journal of Medicine and presented at the American Association for the Study of Liver Diseases’ Liver Meeting 2026.
CIDEBsiRNA is an investigational small interfering RNA (siRNA) therapy designed to reduce the production of a protein associated with liver fat accumulation and metabolic liver disease.
The treatment was developed through a collaboration between Cambridge-based Alnylam and Regeneron, combining Alnylam’s RNA interference technology with genetic research conducted by the Regeneron Genetics Center.
Researchers identified genetic variations in the CIDEB gene associated with liver disease risk, providing the scientific foundation for developing a treatment targeting the gene.
The investigational therapy uses RNA interference, a biological process that prevents the production of specific proteins by silencing the messenger RNA responsible for their creation.
By targeting CIDEB, researchers aim to reduce excess fat accumulation in the liver and potentially address underlying mechanisms contributing to metabolic liver disease.
According to the companies, patients receiving CIDEBsiRNA experienced substantial reductions in liver fat, with some achieving normalization of liver fat levels. Improvements in markers associated with liver injury were also observed.
The reductions were sustained through week 36 following a single administration, suggesting the treatment could offer long-lasting effects without frequent dosing.
“The magnitude and durability of the reductions in liver fat observed with CIDEBsiRNA following a single administration are particularly encouraging and represent an important early signal for the potential of RNAi in treating metabolic liver disease,” said Pushkal Garg, M.D., Chief Research and Development Officer at Alnylam.
“These findings reinforce our conviction that RNAi therapeutics can address a much broader range of diseases than those we treat today. They also demonstrate the value of our partnership model, which allows promising science to advance into new disease areas, reach more patients and create additional opportunities for long-term value.”
Regeneron is leading the ongoing randomized, double-blind, placebo-controlled Phase 1/2 trial involving adults with MASLD and metabolic dysfunction-associated steatohepatitis (MASH), a more severe form of fatty liver disease characterized by inflammation and liver damage.
The study’s primary objective is to assess the safety and tolerability of CIDEBsiRNA, while secondary measures include changes in liver fat content.
Researchers are using magnetic resonance imaging-proton density fat fraction, or MRI-PDFF, to measure changes in liver fat levels during treatment.
Although the initial findings suggest substantial reductions in liver fat, the trial remains in its early stages. Additional research will be needed to determine whether the observed changes translate into sustained clinical benefits, including improvements in liver inflammation, fibrosis and long-term disease outcomes.
Regeneron has led the development of CIDEBsiRNA since the drug candidate was identified in 2023 and holds exclusive commercialization rights.
Under the collaboration agreement, Alnylam is eligible to receive development milestone payments and tiered royalties reaching up to 20% of future sales.
The results also highlight the potential of RNA interference technology to expand beyond its established applications in rare genetic disorders into more common metabolic diseases.
RNA interference works by selectively silencing genes responsible for producing proteins involved in disease. Unlike traditional medicines that primarily act on proteins after they are produced, siRNA therapies target the messenger RNA instructions used to manufacture those proteins.
Alnylam has pioneered the development of RNAi-based medicines, a therapeutic approach rooted in discoveries recognized by the 2006 Nobel Prize in Physiology or Medicine.
CIDEBsiRNA remains investigational and has not been approved for the treatment of MASLD or MASH. Further clinical studies will be required to establish its safety, effectiveness and potential role in managing metabolic liver disease.
