Regeneron CIDEBsiRNA delivers up to 80% liver fat reduction in early MASLD study

Regeneron has reported first-in-human data showing that a single dose of investigational CIDEBsiRNA produced rapid and sustained reductions in liver fat in adults with metabolic dysfunction-associated steatotic liver disease.

Results from the Phase I/II study were presented at AASLD The Liver Meeting 2026 and simultaneously published in The New England Journal of Medicine.

CIDEBsiRNA is a liver-targeted small interfering RNA therapy designed to reproduce the potentially protective effects associated with rare genetic variants in the CIDEB gene identified through the Regeneron Genetics Center.

The first-in-human study evaluated four single-dose levels of CIDEBsiRNA in 30 adults with MASLD, while 10 participants received placebo.

The primary objective was to assess safety and tolerability, with changes in liver fat and markers of liver injury evaluated as secondary endpoints.

At Week 36, patients receiving CIDEBsiRNA experienced dose-dependent liver fat reductions ranging from 58% to 80%.

These reductions deepened over time from decreases of between 49% and 72% observed at Week 6.

By comparison, the placebo group recorded an average liver fat reduction of 2.9% at Week 36.

Liver fat was measured using magnetic resonance imaging-proton density fat fraction.

At Week 36, 62% of CIDEBsiRNA-treated patients had liver fat levels below 5%, which the study defined as normalisation.

None of the patients receiving placebo achieved this threshold.

In addition, 93% of patients treated with CIDEBsiRNA achieved at least a 30% reduction in liver fat.

Regeneron noted that previous analyses of MASH studies have associated reductions of this magnitude with greater likelihood of histological improvement, although the current study did not establish histological MASH resolution.

Improvements were also observed in markers of liver injury.

Mean alanine aminotransferase levels decreased across all CIDEBsiRNA dose groups, with similar directional changes seen in aspartate aminotransferase.

These effects appeared at early timepoints and were maintained through Week 36.

Jörg Täubel, MD, a lead investigator in the study, said the magnitude and duration of the liver fat reductions support further development of CIDEBsiRNA in MASH and other steatotic liver diseases.

He added that effects persisting through 36 weeks could potentially support infrequent dosing, although future studies will be needed to establish an appropriate treatment schedule.

Overall adverse event rates were generally similar between CIDEBsiRNA and placebo.

Most adverse events were mild or moderate.

One CIDEBsiRNA-treated participant experienced severe hyperglycaemia classified as a serious adverse event, but investigators did not attribute it to the study treatment and later associated it with a diagnosis of adult-onset Type 1 diabetes.

No participants discontinued the trial because of adverse events, and no nausea or vomiting events were reported in the CIDEBsiRNA groups.

Regeneron is continuing to evaluate the therapy in additional studies, including ongoing Phase IIa, Phase IIb and Phase III trials.

These studies are assessing longer-term safety and histological outcomes to further determine the treatment’s potential in metabolic dysfunction-associated steatohepatitis and related liver diseases.

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Related Topics and Keywords

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