NGM282, an engineered version of human hormone FGF19 that is administered through a once-daily subcutaneous injection, has demonstrated the ability to rapidly improve NASH and reverse liver fibrosis in clinical and preclinical studies. We believe the combination of breadth, magnitude and speed of effect demonstrated by NGM282 in these studies results in an agent that, if ultimately approved, could provide a needed medicine for physicians to treat NASH patients with moderate to advanced fibrosis. We have tested NGM282 in over 400 subjects, including more than 150 NASH patients, and we expect to initiate a Phase 2b clinical trial in NASH patients in the first quarter of 2019. NGM282 is wholly-owned, and it is not subject to our collaboration with Merck.
NASH is a life threatening form of liver disease. It results from the progression of NAFLD, which is a common co-morbidity of the metabolic syndrome and obesity. NAFLD is characterized by abnormal amounts of fat in the liver, a condition known as steatosis, and is often associated with insulin resistance. This abnormal fat in the liver contributes to the progression by certain NAFLD patients to NASH by developing a necroinflammatory state in the liver that ultimately drives scarring, also known as fibrosis, and, for many, progresses to liver failure, also known as cirrhosis.
The estimated global prevalence of NAFLD and NASH has risen rapidly in parallel with the dramatic rise in population levels of obesity and diabetes. NAFLD now represents the most common cause of liver disease in the Western world. In the United States alone, the prevalence of NASH was estimated to total 16.5 million cases and is projected to reach 27 million cases by 2030, with similar trends occurring globally. By 2020, NASH is expected to supplant hepatitis C as the leading cause for liver transplantation, and liver-related deaths in the NAFLD population are expected to increase by more than 150% in the next 15 years. The annual economic burden associated with NAFLD and NASH in the United States was estimated to have been over $100 billion in 2016.
NGM282 Phase 2 Data Presentation
Stephen Harrison, M.D., Medical Director of Pinnacle Clinical Research, San Antonio, TX, presents NGM282 Phase 2 data, which was originally reported at The International Liver Congress™ 2017.
Download presentation here.
Stephen Harrison, M.D., Medical Director of Pinnacle Clinical Research
Stephen A. Harrison, M.D., presents Phase 2 NGM282 data at the 2017 International Liver Congress™
Effects of NGM282, an FGF19 variant, on colonic transit and bowel function in functional constipation: a randomized phase 2 trial (pdf)
The American Journal of Gastroenterology, 2018
Engineered FGF19 Eliminates Bile Acid Toxicity and Lipotoxicity Leading to Resolution of Steatohepatitis and Fibrosis in Mice (pdf)
Hepatology Communications, 2017
Non-cell-autonomous activation of IL-6/STAT3 signaling mediates FGF19-driven hepatocarcinogenesis
Nature Communications, 2017
Mice Species-specific Control of Hepatocarcinogenesis and Metabolism by FGF19/FGF15
Journal of Hepatology, 2017
Separating Tumorigenicity from Bile Acid Regulatory Activity for Endocrine Hormone FGF19
Cancer Research, 2014
A nontumorigenic Variant of FGF19 Treats Cholestatic Liver Diseases
Science Translational Medicine, 2014
NGM282 Significantly Reduces Hepatic Steatosis Independent of Type 2 Diabetes (T2D) Status or Statin Usage: Results from a Phase 2 Trial in Patients with Nonalcoholic Steatohepatitis (NASH)
(ADA, June 24, 2018)
NGM282 Significantly Reduces Hepatic Steatosis Independent of Baseline Patient Characteristics and Highly Correlates with Markers of FGFR4 Target Engagement: Results from a Phase 2 Trial in Biopsy-Confirmed NASH Patients (R. Loomba, et al, AASLD October 23, 2017)
NGM282 Induces Low Density Lipoprotein Cholesterol (LDLc) Changes, Consistent with Potent FGFR4 Signaling, which are Rapidly Mitigated with Statin Therapy in Patients with Biopsy-Confirmed Nonalcoholic Steatohepatitis (NASH) (M. E. Rinella, et al, AASLD October 23, 2017)
NGM282 Ameliorates Hepatic Lipotoxicity as Measured by Lipidomics and Gene Expression in a Diet-Induced Mouse Model of Nonalcoholic Steatohepatitis (NASH) (L. Ling, et al, AASLD October 23, 2017)
NGM282, a novel variant of FGF19, significantly reduces hepatic steatosis and key biomarkers of NASH: results of a Phase 2, multicenter, randomized, double-blinded, placebo controlled trial in biopsy-confirmed NASH patients (S.A. Harrison, et al, EASL April 22, 2017)
Activation of IL-6/STAT3 Signaling Mediates FGF19-Driven Hepatocarcinogenesis (L. Ling, et al EASL April 21, 2017)
Serum Cholesterol Changes Associated with NGM282 Treatment in Obese Insulin Resistant Cynomolgus Monkeys and NASH Patients are Reversed with Lipid Lowering Agents (Jian Luo, et al, EASL April 21, 2017)
NGM282, A Novel Variant of FGF19, Demonstrates Biologic Activity in Primary Biliary Cirrhosis Patients with an Incomplete Response to Ursodeoxycholic Acid: Results of a Phase 2 Multicenter, Randomized, Double Blinded, Placebo Controlled Trial (M.J. Mayo, et al, AASLD November 16, 2015)
Anti-inflammatory and Antifibrotic Activity of NGM282, A Novel Variant of FGF19, in an Mdr2-Deficient Mouse Model of Primary Sclerosing Cholangitis (L. Ling, et al, AASLD November 16, 2015)
Impact of NGM282 on the Incidence and Severity of Pruritus in Primary Biliary Cirrhosis Patients and Correlations with Liver Chemistries and Serum Bile Acids (M.J. Mayo, et al, AASLD November 14, 2015; Poster)
FGF15 and FGF19 Induce Disparate FGFR4-Mediated Hepatocarcinogenicity In Vitro and In Two Murine Models: Implications for Drug-Associated Carcinogenicity Risk Assessments (L. Ling, et al, AASLD November 17, 2015; Poster)