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Single administration of CIDEBsiRNA resulted in rapid, deep and durable reductions in liver fat by up to 80% that were sustained through 36 weeks
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Data from first-in-human trial were shared in oral presentation at AASLD The Liver Meeting® and simultaneously published in The New England Journal of Medicine
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Regeneronto host virtual “Regeneron Roundtable” investor event to discuss its MASH pipeline programs onTuesday, November 10at8:30 a.m. ET
TARRYTOWN, N.Y.,Nov. 08, 2026(GLOBE NEWSWIRE) --Regeneron Pharmaceuticals, Inc.(NASDAQ: REGN) today announced the first results from a first-in-human trial that demonstrated a single subcutaneous dose of CIDEBsiRNA rapidly normalized liver fat and improved liver injury markers in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) with effects that were sustained through week 36. CIDEBsiRNA is an investigational, first-in-class, liver-targeted small interfering RNA (siRNA) therapeutic that mimics the protective effect of rare mutations in the CIDEB gene, which were discovered by theRegeneronGenetics Center®. The results were published by The New England Journal of Medicineand simultaneously presented in an oral session at the American Association for the Study of Liver Diseases (AASLD)The Liver Meeting® 2026.
“Prior advances in steatotic liver disease have begun to make a difference, but there is so much more progress to be made to help patients normalize liver fat and reverse liver damage,” said Jörg Täubel, M.D., F.F.P.M., F.E.S.C., Executive Chairman ofRichmond Pharmacology, Visiting Professor atKing’s College London, Honorary Senior Research Fellow at St. George’s University inLondon, President ofThe Association for Applied Human Pharmacologyand a lead investigator for the trial. “These results show CIDEBsiRNA resulted in rapid, deep and sustained reductions in liver fat with improvements in markers of liver injury. With effects out to 36 weeks that support the potential for twice-yearly dosing, alongside the safety profile, the findings highlight CIDEBsiRNA as a promising new therapeutic for MASH and other steatotic liver diseases.”
MASLD occurs when excess fat accumulates in the liver and encompasses a spectrum of conditions ranging from simple fatty liver to the more serious disease of metabolic dysfunction-associated steatohepatitis (MASH). MASH is a progressive, fibrotic liver disease that affects approximately 13 millionU.S. adults, which is characterized by inflammation and cell damage that can lead to cirrhosis, liver transplant, liver cancer and death if not properly managed. Historical clinical trial data report that currently approved MASH therapies have reached mean liver fat reductions of 47-57% at approximately one year.1,2
A first-in-human, Phase 1/2 trial evaluated a single subcutaneous dose of CIDEBsiRNA at four dose levels (n=30 for CIDEBsiRNA groups) versus placebo (n=10) in adults with MASLD. The primary goal of the trial was to evaluate safety and tolerability, with liver fat and markers of liver injury evaluated as secondary endpoints. Meta-analyses of clinical trials of patients with MASH indicate that the depth of liver fat reduction correlates with liver biopsy response (e.g., MASH resolution and fibrosis improvement), supporting changes in liver fat as an informative, early pharmacodynamic readout.
Results for CIDEBsiRNA recipients showed:
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58-80% dose-dependent liver fat reductions at week 36, which had deepened from the rapid 49-72% reductions at week 6 (as measured by magnetic resonance imaging-proton density fat fraction, MRI-PDFF). Mean decrease in the placebo group was 2.9% at week 36.
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Liver fat was normalized in a majority (62%) of CIDEBsiRNA recipients at week 36 (defined as liver fat content under 5% by MRI-PDFF) versus none in the placebo group. Additionally, 93% had reductions of liver fat of ≥30%, a threshold linked to histological MASH resolution.
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Improvements were seen in markers of liver injury at early timepoints and sustained through week 36, with reductions in mean levels of alanine aminotransferase (ALT) across all doses and directionally similar changes in aspartate aminotransferase (AST) levels.
Overall rates of adverse events (AEs) were generally similar between the CIDEBsiRNA and placebo groups. All AEs were mild or moderate in severity, except for a severe, serious event of hyperglycemia in a CIDEBsiRNA-treated participant that was not attributed to study drug (instead later attributed to a diagnosis of adult-onset Type 1 diabetes). There were no trial discontinuations and no nausea or vomiting AEs reported in the CIDEBsiRNA groups, addressing a key tolerability limitation associated with other therapies.
Longer-term safety and histologic outcomes are being evaluated in multiple, ongoing trials, including Phase 2a, Phase 2b and Phase 3 trials that are now recruiting.Regeneronis also investigating additional drug candidates informed by human genetics for the treatment of steatotic liver diseases.
The potential uses of CIDEBsiRNA described above are investigational, and its safety and efficacy have not been evaluated by any regulatory authority.
About the “Regeneron Roundtable” Investor Event
Regeneronwill host a virtual investor event to discuss its cardiometabolic and MASH pipeline programs onTuesday, November 10at8:30 a.m. ET. This is the next webcast in an investor event series called the “Regeneron Roundtable,” intended to highlight programs from the company’s innovative investigational pipeline.
Links to the webcast and to register via telephone may be accessed from the ‘Investors and Media’ page of Regeneron’s website at https://investor.regeneron.com/events-and-presentations. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number, along with a unique passcode and registrant ID that can be used to access the call. A replay of the conference call and webcast will be archived on the company’s website for at least 30 days.
About CIDEBsiRNA, the trial and theRegeneronMASLD/MASH Program
CIDEBsiRNA is an investigational, first-in-class, liver-targeted siRNA therapeutic that targets a receptor exclusively expressed in the liver to mimic the protective effect of naturally occurring loss-of-function and missense CIDEB mutations in a broad population of people with MASLD and MASH.
The ongoing Phase 1/2 randomized, double-blind, placebo-controlled trial is evaluating the safety and tolerability of CIDEBsiRNA in adult participants with MASLD and MASH. The primary goal of the trial is to evaluate safety and tolerability with efficacy evaluated as a secondary endpoint through measures such as change in liver fat fraction by MRI-PDFF.
Scientists at theRegeneronGenetics Center® (RGC) analyzed genetic data to discover and/or validate genetic variants in the CIDEB and other genes that are associated with liver disease risk. Building on these findings,Regeneroncollaborated with Alnylam to generate an siRNA targeting CIDEB and has the exclusive rights for the development of and commercialization of CIDEBsiRNA; Alnylam receives milestone and royalty payments.
About Regeneron
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous approved treatments and product candidates in development, most of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, neurological diseases, hematologic conditions, infectious diseases, and rare diseases.
Regeneron pushes the boundaries of scientific discovery and accelerates drug development using our proprietary technologies, such as VelociSuite®, which produces optimized fully human antibodies and new classes of bispecific antibodies. We are shaping the next frontier of medicine with data-powered insights from the Regeneron Genetics Center® and pioneering genetic medicine platforms, enabling us to identify innovative targets and complementary approaches to potentially treat or cure diseases.
1 Harrison SA, Bedossa P, Guy CD, et al. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis. N Engl J Med. 2024;390(6):497-509. doi:10.1056/NEJMoa2309000.
2 Flint A, Andersen G, Hockings P, et al. Randomised clinical trial: semaglutide versus placebo reduced liver steatosis but not liver stiffness in subjects with non-alcoholic fatty liver disease assessed by magnetic resonance imaging. Aliment Pharmacol Ther. 2021;54(9):1150-1161. doi:10.1111/apt.16608.