MK-3655 / Merck (MSD), NGM Biopharma - LARVOL DELTA

Clinical Trial: A Phase 2b Study to Evaluate the Efficacy and Safety of MK-3655 in Individuals With Pre-Cirrhotic MASH. (PubMed, Aliment Pharmacol Ther) - P2 | "In patients with pre-cirrhotic MASH, treatment with MK-3655 resulted in a modest reduction in LFC at 24 weeks."

Journal • P2b data • Diabetes • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Type 2 Diabetes Mellitus • FGF21

A Study of MK-3655 in Individuals With Pre-cirrhotic Nonalcoholic Steatohepatitis (NASH) (MK-3655-001) (clinicaltrials.gov) - P2 | N=183 | Terminated | Sponsor: Merck Sharp & Dohme LLC | Phase classification: P2b ➔ P2

Phase classification • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis

A Study of MK-3655 in Individuals With Pre-cirrhotic Nonalcoholic Steatohepatitis (NASH) (MK-3655-001) (clinicaltrials.gov) - P2b | N=187 | Terminated | Sponsor: Merck Sharp & Dohme LLC | N=328 ➔ 187 | Active, not recruiting ➔ Terminated; Business reasons

Enrollment change • Trial termination • Hepatology • Non-alcoholic Steatohepatitis

A Study of MK-3655 in Individuals With Pre-cirrhotic Nonalcoholic Steatohepatitis (NASH) (MK-3655-001) (clinicaltrials.gov) - P2b | N=328 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Aug 2024 ➔ Apr 2023 | Trial primary completion date: Aug 2024 ➔ Apr 2023

Trial completion date • Trial primary completion date • Hepatology • Non-alcoholic Steatohepatitis

A Study of MK-3655 in Individuals With Pre-cirrhotic Nonalcoholic Steatohepatitis (NASH) (MK-3655-001) (clinicaltrials.gov) - P2b | N=328 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatology • Non-alcoholic Steatohepatitis

A Study of MK-3655 in Individuals With Pre-cirrhotic Nonalcoholic Steatohepatitis (NASH) (MK-3655-001) (clinicaltrials.gov) - P2b | N=328 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | Trial completion date: Sep 2023 ➔ May 2024 | Trial primary completion date: Sep 2023 ➔ May 2024

Trial completion date • Trial primary completion date • Hepatology • Non-alcoholic Steatohepatitis

A Study of MK-3655 in Individuals With Pre-cirrhotic Nonalcoholic Steatohepatitis (NASH) (MK-3655-001) (clinicaltrials.gov) - P2b; N=328; Recruiting; Sponsor: Merck Sharp & Dohme Corp.; Trial completion date: Feb 2023 ➔ Sep 2023; Trial primary completion date: Feb 2023 ➔ Sep 2023

Clinical • Trial completion date • Trial primary completion date • Hepatology • Non-alcoholic Steatohepatitis

A Study of MK-3655 in Individuals With Pre-cirrhotic Nonalcoholic Steatohepatitis (NASH) (MK-3655-001) (clinicaltrials.gov) - P2b; N=328; Recruiting; Sponsor: Merck Sharp & Dohme Corp.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Hepatology • Non-alcoholic Steatohepatitis

Phase 2b Study of MK-3655 in Individuals with Pre cirrhotic Nonalcoholic Steatohepatitis (NASH) (clinicaltrialsregister.eu) - P2; N=328; Ongoing; Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Clinical • New P2 trial • Hepatology • Metabolic Disorders • Non-alcoholic Steatohepatitis • MRI

A Study of MK-3655 in Individuals With Pre-cirrhotic Nonalcoholic Steatohepatitis (NASH) (MK-3655-001) (clinicaltrials.gov) - P2b; N=328; Not yet recruiting; Sponsor: Merck Sharp & Dohme Corp.

Clinical • New P2b trial • Hepatology • Non-alcoholic Steatohepatitis

NGM313, a Novel Activator of b-Klotho/FGFR1c, Improves Insulin Resistance and Reduces Hepatic Fat in Obese, Nondiabetic Subjects (ADA 2019) - "This study compared the effects of a single dose of NGM313 vs. daily pioglitazone (PIO) on insulin sensitivity, liver fat content (LFC) and lipids in insulin resistant, obese subjects with increased liver fat. 25 subjects were randomized 2:1 to either a single dose of NGM313 240 mg SC (n=17) or PIO 45 mg PO QD (n=8) for 36 days. NGM313 is a potent insulin sensitizer, comparable to PIO. In addition, NGM313 is highly effective in reducing LFC in subjects with increased liver fat. As such, NGM313 has significant potential to be an effective treatment for nonalcoholic steatohepatitis and type 2 diabetes."

Clinical • Late-breaking abstract

NGM313, a novel activator of beta-Klotho/FGFR1c: A single dose significantly reduces steatosis (liver fat by MRI-PDFF), inflammation (ALT, AST) and fibrogenic activity (Pro-C3) in NAFLD subjects (EASL-ILC 2019) - "Insulin sensitizers have demonstrated decreases in hepatic steatosis, inflammation and fibrosis in patients with NASH, but pioglitazone (PIO) has limited use due to heart failure, weight gain, edema and fractures. A single dose of NGM313 demonstrated improvements in insulin sensitivity, FPG and lipids coupled with rapid and significant reductions in LFC, ALT, AST and Pro-C3. There were no identified safety or tolerability signals. These data support further evaluation of NGM313 in patients with biopsy-confirmed NASH.Figure: Table 1."

Clinical

NGM313 shows ‘acute and significant’ reductions in NASH markers (Healio) - P1, N=25; "Single dose NGM313 also reduced pro-C3 at a midpoint in the study between day 23 and day 28 (–1.29 ng/mL; P < .05), whereas pioglitazone did not affect pro-C3. Both drugs demonstrated a favorable safety and tolerability profile with all adverse events considered mild."

Biomarker

Study of NGM313 in Obese Participants (clinicaltrials.gov) - P1b; N=25; Completed; Sponsor: NGM Biopharmaceuticals, Inc; Recruiting ➔ Completed; Trial completion date: Dec 2018 ➔ Jul 2018; Trial primary completion date: Dec 2018 ➔ Jun 2018

Clinical • Trial completion • Trial completion date • Trial primary completion date

"#EASL2019 #ILC2019 abstract titles out #NASH/NAFLD continues to be the big focus $MNK $TAK AMITIZA $NGM-313 FGFR1c/KLB agonist $CSTX MSDC-0602K $PFE Big show w/ 3 diff MoA: KHKi/DGAT2i/ACCi Other data $ALNY Givosiran Ph3 $GKTX Ph2 PBC IBATi showdown in #Alagille $ALBO vs Mirum" (@AndyBiotech)

P2 data