cenicriviroc/tropifexor (LJC242) / Novartis, AbbVie - LARVOL DELTA

MASH 2B TRIALS- A SYSTEMATIC REVIEW (AASLD 2024) - "These include PPAR agonists, SGLT-2 inhibitors, GLP-1 inhibitors, and the recently approved Resmetirom...The Harmony trial with efruxifermin showed significant fibrosis improvement, while the Enliven trial with pegozafermin also demonstrated significant fibrosis reduction at higher doses...Alpine 2/3 and Alpine 4 trials with aldafermin showed mixed results, with significant fibrosis improvement only in specific doses. The TANDEM trial, comparing Tropifexor and Cenicriviroc, focused on safety and efficacy, showing ALT, AST, and GGT reductions... RCTs in NASH treatment showed mixed outcomes. Lanifibranor and icosabutate showed promise, especially in T2D patients. FGF21 analogues like efruxifermin improved fibrosis, while FGF19 trials had variable results."

Review • Fatigue • Fibrosis • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Pain • Solid Tumor • Type 2 Diabetes Mellitus • FGF19 • FGF21

COMPARATIVE EFFICACY OF PHARMACOLOGIC THERAPIES FOR MASH IN REDUCING LIVER FAT CONTENT: SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS (AASLD 2024) - "By comparison of absolute MRI-PDFF decline at 24 weeks, aldafermin (SUCRA: 83.65), pegozafermin (SUCRA: 83.46), and pioglitazone (SUCRA: 71.67) were the most efficacious interventions. Efinopegdutide (SUCRA: 67.02), semaglutide + firsocostat (SUCRA: 62.43), and pegbelfermin (SUCRA: 61.68) were the most efficacious interventions for achieving ≥30% decline in MRI-PDFF at 24 weeks...Efruxifermin, aldafermin and pegozafermin were the most efficacious for MRI-PDFF decline at 12 weeks by both the absolute decline and achieving ≥30% decline in MRI-PDFF. At 48 weeks, Cilofexor + firsocostat, selonternib + firsocostat and cilofexor were most efficacious in absolute reduction in MRI-PDFF, while semglutide, tropifexor and tropifexor + cenicriviroc were most efficacious in achieving ≥30% decline in MRI-PDFF... This study provides an updated, relative rank-order efficacy of therapies for MASH in reducing hepatic fat as assessed by MRI-PDFF. These data may help inform the design and..."

Retrospective data • Review • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

Comparative efficacy of pharmacologic therapies in MASH: Systematic review and meta-analysis (APASL 2024) - "Aldafermin had the highest probability of being ranked as the most effective intervention for MRI-PDFF decline (SUCRA = 89.59), followed by Pegozafermin (SUCRA = 88.99), and Pioglitazone (SUCRA = 61.41) at week 24. For MRI-PDFF response, Aldafermin (SUCRA = 92.61), Efruxifermin (SUCRA = 81.00) and Resmetirom (SUCRA = 55.54) had the highest probability of being ranked the most effective intervention for achieving MRI-PDFF response at week 12. These data provide relative rank-order efficacy of various MASH therapies in terms of improvements in MRI-PDFF."

Retrospective data • Review • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Tropifexor plus cenicriviroc combination versus monotherapy in non-alcoholic steatohepatitis: Results from the Phase 2b TANDEM study. (PubMed, Hepatology) - "The safety profile of TXR + CVC combination was similar to respective monotherapies, with no new signals. TXR monotherapy showed sustained ALT and body weight decreases. No substantial incremental efficacy was observed with TXR + CVC combination on ALT, body weight, or in histological endpoints compared with monotherapy."

Journal • Monotherapy • P2b data • Dermatology • Fibrosis • Hepatology • Immunology • Non-alcoholic Steatohepatitis • Pruritus

[VIRTUAL] SAFETY AND EFFICACY OF TROPIFEXOR PLUS CENICRIVIROC COMBINATION THERAPY IN ADULT PATIENTS WITH FIBROTIC NASH: 48 WEEK RESULTS FROM THE PHASE 2b TANDEM STUDY (AASLD 2021) - P2 | "Combination therapy with TXR+CVC was safe and well tolerated compared to TXR and CVC monotherapy up to W48 . TXR alone or in combination with CVC showed sustained decrease in ALT and body weight, consistent with results of other FXR studies . COVID-19 restrictions introduced mid- study may have attenuated effects seen with TXR on weight loss ."

Clinical • Combination therapy • P2b data • Dermatology • Fibrosis • Hepatology • Immunology • Infectious Disease • Liver Cirrhosis • Non-alcoholic Steatohepatitis • Novel Coronavirus Disease • Pruritus • MRI

Tropifexor safe up to 48 weeks for NASH (Healio) - P2; N=152; FLIGHT-FXR (NCT02855164); "'The role of tropifexor as part of a combination therapy indicated for the treatment of fibrotic NASH is also being investigated in ongoing studies,' Arun J. Sanyal, MD...'A higher proportion of patients in the tropifexor groups achieved a greater than 30% hepatic fat fraction reduction vs. placebo,' Sanyal said. 'Dose-dependent decreases in total [NAFLD activity score] and modest improvement resolution without worsening of fibrosis were seen.'"

Media quote • P2 data

Safety, Tolerability, and Efficacy of a Combination Treatment of Tropifexor (LJN452) and Cenicriviroc (CVC) in Adult Patients With Nonalcoholic Steatohepatitis (NASH) and Liver Fibrosis. (TANDEM) (clinicaltrials.gov) - P2; N=193; Completed; Sponsor: Novartis Pharmaceuticals; Active, not recruiting ➔ Completed

Clinical • Trial completion • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Non-alcoholic Steatohepatitis

Safety, Tolerability, and Efficacy of a Combination Treatment of Tropifexor (LJN452) and Cenicriviroc (CVC) in Adult Patients With Nonalcoholic Steatohepatitis (NASH) and Liver Fibrosis. (TANDEM) (clinicaltrials.gov) - P2; N=194; Active, not recruiting; Sponsor: Novartis Pharmaceuticals; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis

A randomized, double-blind, multicenter, phase 2b study to evaluate the safety and efficacy of a combination of tropifexor and cenicriviroc in patients with nonalcoholic steatohepatitis and liver fibrosis: Study design of the TANDEM trial. (PubMed, Contemp Clin Trials) - P2; "TANDEM will evaluate the combination of TXR and CVC with respect to safety and efficacy outcomes related to improvement in fibrosis or resolution of steatohepatitis. Given the effects of TXR and CVC in multiple pathophysiological pathways associated with NASH, combination therapy is likely to show additional benefits compared with monotherapy."

Clinical • Journal • P2b data

Allergan and cenicriviroc in NASH: The forgotten (SeekingAlpha) - “The top-line Phase 3 interim data readout on the 52-week study of cenicriviroc in patients with biopsied NASH fibrosis should be announced by Q4 2020...CVC is also being clinically evaluated in combination with tropifexor by Novartis (NVS) in a Phase 2 NASH fibrosis trial. The top-line data is also anticipated in Q4 2020."

P2 data • P3 data: top line

Newly added product (Novartis Press Release) - P2, Non-alcoholic Steatohepatitis

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