Regeneron advances CIDEB siRNA in MASLD

Regeneron Pharmaceuticals (REGN) has announced positive first-in-human Phase 1/2 results for its investigational CIDEB-targeting small interfering RNA (siRNA), also known as ALN-CIDEB, in adults with metabolic dysfunction-associated steatotic liver disease and MASH. A single subcutaneous dose across four dose levels in 30 treated participants reduced liver fat by 58% to 80% at week 36, compared with a 2.9% mean decrease among 10 placebo recipients, as measured by MRI-PDFF.

At week 36, liver fat levels fell below 5% in 62% of CIDEB siRNA recipients, while none of the placebo group reached this threshold. Overall, 93% of treated participants achieved at least a 30% reduction in liver fat, a level associated with histological MASH resolution, underscoring the consistency of response in this early-stage trial.

The first-in-human trial evaluated a single dose of CIDEB siRNA given at four dose levels to 30 participants and compared outcomes with 10 placebo recipients. Safety and tolerability were the primary objectives, while changes in liver fat and liver-injury markers such as ALT and AST served as secondary measures. Initial reductions in liver fat of 49% to 72% were observed as early as week six and were sustained, reaching 58% to 80% by week 36.

Improvements in ALT and directionally similar changes in AST were maintained through week 36, indicating that the effect extended beyond fat reduction to markers of liver injury. These data remain early clinical evidence and the study has not yet established whether treatment improves liver fibrosis or resolves MASH, leaving longer-term histologic outcomes to ongoing studies.

Across the trial, overall adverse event rates were generally similar between the CIDEB siRNA and placebo groups. Most adverse events were mild or moderate in severity. There was one severe, serious case of hyperglycemia in a treated participant, which was later attributed to adult-onset Type 1 diabetes rather than the investigational drug, and no participants discontinued treatment due to adverse events.

Regeneron reported that the sustained liver fat reductions through week 36 support the potential for less frequent dosing, including an every-six-month schedule, although no definitive dosing regimen has been clinically established. The findings have been published in The New England Journal of Medicine and presented at AASLD The Liver Meeting 2026, highlighting the growing clinical interest in this mechanism.

CIDEB siRNA is designed to mimic the protective effects of rare CIDEB gene mutations identified by the Regeneron Genetics Center, which are associated with reduced susceptibility to liver disease. Regeneron holds exclusive development and commercialization rights to the program following a collaboration with Alnylam Pharmaceuticals, under which Alnylam is eligible for milestone and royalty payments.

The company is advancing CIDEB siRNA into larger and longer-term studies, including a registered Phase IIb trial in fibrotic MASH with 132 participants and a Phase III trial in MASLD enrolling 1,500 participants. Longer-term safety and histologic outcomes are being evaluated in ongoing Phase 2a, Phase 2b and Phase 3 studies. Regeneron has scheduled a virtual investor event, the Regeneron Roundtable, for November 10 at 8:30 a.m. Eastern time to discuss its cardiometabolic and MASH pipeline, with the CIDEB program a key area of focus.