nidufexor (LMB763) / Novartis - LARVOL DELTA

Pharmacological characterization of second generation FXR agonists as effective EphA2 antagonists: a successful application of target hopping approach. (PubMed, Biochem Pharmacol) - "Herein we characterize new commercially available FXR (Farnesoid X Receptor) agonists as potential Eph ligands including Cilofexor, Nidufexor, Tropifexor, Turofexorate isopropyl and Vonafexor. Furthermore, Cilofexor interferes with the phosphorylation of EphA2 and the cell retraction and rounding in PC3 prostate cancer cells, both events depending on EphA2 activation. In conclusion, we can confirm that target hopping can be a successful approach to discover new moiety of protein-protein inhibitors."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Potential for FDA approval nears for emerging NASH therapies (Healio) - "'We [have] a huge armamentarium of drugs in development,' Manal F. Abdelmalek, MD...'In my opinion, the future of NASH is going to be binding combination therapies, for which we have a foundation of anti-metabolic therapy, coupled with anti-inflammatory or anti-fibrotic therapy, depending on where patients are in the disease spectrum.'"

Media quote

Safety, Tolerability and Efficacy of Nidufexor in Patients With Diabetic Nephropathy (clinicaltrials.gov) - P2; N=83; Completed; Sponsor: Novartis Pharmaceuticals; Recruiting ➔ Completed; Trial completion date: May 2022 ➔ May 2021; Trial primary completion date: May 2022 ➔ May 2021

Clinical • Trial completion • Trial completion date • Trial primary completion date • Diabetic Nephropathy • Nephrology • Renal Disease

The identification of farnesoid X receptor modulators as treatment options for non-alcoholic fatty liver disease. (PubMed, Expert Opin Drug Discov) - "FXR agonists that are currently undergoing phase2/3 trials are cilofexor, tropifexor, nidufexor and MET409. Some of these agents are currently developed as combination therapies with other agents including cenicriviroc, a CCR2/CCR5 inhibitor, or firsocostat an acetyl CoA carboxylase inhibitor. Additional investigations are needed to evaluate the beneficial effects of combination of these agents with statins. It is expected that in the coming years, FXR agonists will be developed as a combination therapy to minimize side effects and increase likelihood of success by targeting different metabolic pathways."

Journal • Cardiovascular • Dermatology • Hepatology • Non-alcoholic Fatty Liver Disease • Pruritus

Safety, Tolerability and Efficacy of Nidufexor in Patients With Diabetic Nephropathy (clinicaltrials.gov) - P2; N=116; Recruiting; Sponsor: Novartis Pharmaceuticals; Trial completion date: Dec 2021 ➔ May 2022; Trial primary completion date: Dec 2021 ➔ May 2022

Clinical • Trial completion date • Trial primary completion date • Diabetic Nephropathy • Nephrology • Renal Disease

Nidufexor (LMB763), a Novel FXR Modulator for the Treatment of Nonalcoholic Steatohepatitis (NASH). (PubMed, J Med Chem) - "While there are currently no approved therapies for NASH, the bile acid-derived FXR agonist obeticholic acid (OCA; 6-ethyl chenodeoxycholic acid) has shown promise in clinical studies. Previously, we described the discovery of tropifexor (LJN452), the most potent non-bile acid FXR agonist currently in clinical investigation. Here, we report the discovery of a novel chemical series of non-bile acid FXR agonists based on a tricyclic dihydrochromenopyrazole core from which emerged nidufexor (LMB763), a compound with partial FXR agonistic activity in vitro and FXR-dependent gene modulation in vivo. Nidufexor has advanced to Phase 2 human clinical trials in patients with NASH and diabetic nephropathy."

Journal • Addiction (Opioid and Alcohol) • Diabetic Nephropathy • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Nephrology • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Renal Disease

"Nidufexor significantly reduces ALT levels, hepatic fat in NASH https://t.co/D1wuYtZG9t" (@KowdleyMd)

Hepatology • Non-alcoholic Steatohepatitis

[VIRTUAL] Nidufexor, a non-bile acid FXR agonist, decreases ALT and hepatic fat fraction in patients with NASH after 12 weeks dosing (EASL-ILC-I 2020) - "In patients with NASH, both dosages of nidufexor appeared safe and were associated with significant reductions in ALT levels, hepatic fat fraction and body weight. The most frequent AE was pruritus, which was more common at 100 mg nidufexor. There were no meaningful changes in total cholesterol, LDL-C or triglycerides, although HDL-C decreased in both active groups."

Clinical • Dermatology • Hepatology • Non-alcoholic Steatohepatitis • Pruritus • Renal Disease

Bile acid modulators for the treatment of nonalcoholic steatohepatitis (NASH). (PubMed, Expert Opin Investig Drugs) - "EDP305, tropifexor, cilofexor, nidufexor, TERN.101, Px-104, EYP001, MET409...Efficacy of combining an FXR agonist with statins, CCR2, and ACC inhibitors is currently investigated. Identification of patient subsets would allow development of patients tailored therapy using a combination of drugs acting on different molecular mechanisms."

Journal • Addiction (Opioid and Alcohol) • Dermatology • Fibrosis • Hepatology • Immunology • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Pruritus

Safety, Tolerability and Efficacy of LMB763 in Patients With Diabetic Nephropathy (clinicaltrials.gov) - P2; N=116; Recruiting; Sponsor: Novartis Pharmaceuticals; Trial completion date: Sep 2021 ➔ Dec 2021; Trial primary completion date: Sep 2021 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Renal Disease

Safety, Tolerability, Pharmacokinetics and Efficacy of LMB763 in Patients With NASH (clinicaltrials.gov) - P2; N=122; Terminated; Sponsor: Novartis Pharmaceuticals; Completed ➔ Terminated

Clinical • Trial termination • MRI

Safety, Tolerability and Efficacy of LMB763 in Patients With Diabetic Nephropathy (clinicaltrials.gov) - P2; N=116; Recruiting; Sponsor: Novartis Pharmaceuticals; Trial completion date: Oct 2022 ➔ Sep 2021; Trial primary completion date: Oct 2022 ➔ Sep 2021

Clinical • Trial completion date • Trial primary completion date

Safety, Tolerability, Pharmacokinetics and Efficacy of LMB763 in Participants With NASH (clinicaltrials.gov) - P2; N=121; Completed; Sponsor: Novartis Pharmaceuticals; Trial completion date: Sep 2018 ➔ Mar 2019

Clinical • Trial completion date

Safety, Tolerability and Efficacy of LMB763 in Patients With Diabetic Nephropathy (clinicaltrials.gov) - P2; N=116; Recruiting; Sponsor: Novartis Pharmaceuticals; Trial completion date: Jul 2021 ➔ Oct 2022; Trial primary completion date: Jul 2021 ➔ Oct 2022

Clinical • Trial completion date • Trial primary completion date

Safety, Tolerability, Pharmacokinetics and Efficacy of LMB763 in Patients With NASH (clinicaltrials.gov) - P2; N=122; Completed; Sponsor: Novartis Pharmaceuticals; Terminated ➔ Completed

Clinical • Trial completion

Safety, Tolerability, Pharmacokinetics and Efficacy of LMB763 in Patients With NASH (clinicaltrials.gov) - P2; N=122; Terminated; Sponsor: Novartis Pharmaceuticals; N=192 ➔ 122; Trial completion date: Dec 2019 ➔ Sep 2018; Active, not recruiting ➔ Terminated; Trial primary completion date: Dec 2019 ➔ Aug 2018

Enrollment change • Trial completion date • Trial primary completion date • Trial termination

Safety, tolerability and efficacy of LMB763 in patients with diabetic nephropathy (clinicaltrialsregister.eu) - P2; N=116; Ongoing; Sponsor: Novartis Pharma AG

Clinical • New P2 trial

Safety, Tolerability, Pharmacokinetics and Efficacy of LMB763 in Patients With NASH (clinicaltrials.gov) - P2; N=192; Active, not recruiting; Sponsor: Novartis Pharmaceuticals; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

Safety, Tolerability and Efficacy of LMB763 in Patients With Diabetic Nephropathy (clinicaltrials.gov) - P2; N=100; Recruiting; Sponsor: Novartis Pharmaceuticals

Clinical • New P2 trial