Regeneron Pharmaceuticals (NASDAQ:REGN) is advancing its experimental CIDEB therapy into later-stage studies for a form of liver disease after an early trial showed a single dose substantially reduced liver fat, executives said during an investor event.
The company said its phase 2b study in patients with fibrotic metabolic dysfunction-associated steatohepatitis, or MASH, and a phase 3 safety study in patients with metabolic dysfunction-associated steatotic liver disease, or MASLD, are underway. Regeneron expects final data from the phase 2b study in 2029 and plans to discuss its registration pathway with regulators.
The CIDEB program emerged from research at the Regeneron Genetics Center, which uses human genetic data to identify potential drug targets. Regeneron developed the small interfering RNA, or siRNA, treatment through its collaboration with Alnylam.
Early Results and the Path to Approval
In the placebo-controlled portion of a first-in-human study, a single injection of CIDEB siRNA reduced liver fat by as much as 80%, with reductions sustained through 36 weeks, said Gary Herman, senior vice president and clinical development unit head for Regeneron Genetic Medicines. At week 12, mean liver fat was near or below the upper limit of normal at every tested dose, he said.
Herman said the treatment was generally well tolerated through 36 weeks, with adverse event rates similar to placebo. No nausea or vomiting was reported in the CIDEB treatment groups, and the company saw no evidence of increases in serum triglycerides or LDL cholesterol.
During the question-and-answer session, Herman said Regeneron had not seen clear treatment-related effects on glucose or hemoglobin A1C. Thomas Norton, executive medical director of clinical sciences, said one serious hyperglycemic event occurred in a patient with preexisting diabetes and was assessed by the investigator as unrelated to the study drug.
Regeneron executives cautioned that further studies must establish whether the observed reductions in liver fat translate into improvements in liver tissue and clinical outcomes. Herman said liver biopsy measures remain the registration endpoints for MASH, although the company is open to discussing non-invasive measures with the Food and Drug Administration.
The phase 2b study is intended to assess liver fat reduction, MASH resolution and fibrosis improvement by biopsy at 52 weeks in patients with F2 or F3 fibrosis. George Yancopoulos, Regeneron’s co-founder, president and chief scientific officer, said interim analyses could offer an opportunity to accelerate timing, pending discussions with the FDA. The company did not provide a filing date.
Genetics Guides Pipeline
Regeneron’s researchers identified a rare loss-of-function variant in the CIDEB gene carried by approximately one in 500 people. Aris Baras, head of the Regeneron Genetics Center, said carriers had a 43% lower risk of developing liver disease and 22% lower liver fat.
Baras said the genetics center has enabled the discovery or validation of nearly 50 targets since 2015, with programs for six of those targets now in clinical development. Regeneron has access to data from nearly 4 million sequenced participants, including approximately 3.3 million generated in-house, he said.
In addition to CIDEB, Regeneron is prioritizing its PNPLA3 siRNA program for patients with two copies of a specific genetic risk variant. Herman said a phase 2 trial is underway to assess the treatment in combination with a GLP-1-based therapy in MASLD. The company is deprioritizing its HSD siRNA program based on comparative genetic and clinical data.
Regeneron also described a protein-based risk score that it is studying as a potential non-invasive alternative to liver biopsy. Baras said the score predicted similar 10-year clinical event rates to biopsy in the cohort discussed. Yancopoulos said the company is still considering questions about its potential adoption and regulatory use.
Market Opportunity
Herman estimated that MASH affects roughly 13 million U.S. adults and said fewer than 10% of addressable patients are diagnosed. The company’s initial focus is patients with F2 or F3 fibrosis, a population Josh Adelson, executive director of commercial and new products, estimated at 5 million to 5.5 million U.S. adults.
Adelson said Regeneron estimates the U.S. MASH market at approximately $1 billion in net sales and projects it could reach $15 billion or more by 2035 as diagnosis and treatment increase. He said CIDEB could potentially be administered every six months and used alone or alongside GLP-1 therapies, subject to further clinical validation.
About Regeneron Pharmaceuticals (NASDAQ:REGN)
Regeneron Pharmaceuticals, Inc is a biotechnology company that discovers, develops, manufactures and commercializes medicines for serious diseases. Its research and product portfolio spans areas including eye disease, allergic and inflammatory conditions, cancer, cardiovascular and metabolic disorders, infectious diseases and rare conditions.
The company’s medicines include EYLEA for certain eye diseases, Dupixent for inflammatory conditions and Libtayo for cancer. Regeneron also develops and markets treatments with pharmaceutical partners, including Sanofi, and its products reach patients in the United States and international markets through its own operations and collaborations.
Founded in 1988, Regeneron is headquartered in Tarrytown, New York.
