cenicriviroc (TBR-652) / Dong-A, Takeda, AbbVie - LARVOL DELTA

Fibrogenic Gene Signature as Early Prediction for the Efficacy of Pharmacological Interventions for MASH-Associated Fibrosis. (PubMed, FASEB J) - "Mice were subsequently treated for 4 weeks with various therapeutics with established efficacy (obeticholic acid) or lack of efficacy (cenicriviroc and pioglitazone) to study their anti-fibrotic potential. This study highlights the potential of using short-term studies and applying a fibrogenic gene signature as an early screening tool to investigate the efficacy of investigative drugs on MASH-associated fibrosis. This signature, which is based on the active fibrosis processes in humans, may allow rapid screening of therapeutics, or combinations thereof, when used in a translational mouse model."

Gene Signature • Journal • Fibrosis • Genetic Disorders • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

Understanding residual risk of cardiovascular disease in people with HIV. (PubMed, Curr Opin HIV AIDS) - "Despite antiretroviral and statin therapy, residual ASCVD risk in PWH underscores the need for targeted interventions. Anti-inflammatory therapies, including IL-6 and IL-1β inhibitors, CCR5 antagonists (e.g., maraviroc, cenicriviroc mesylate), and immunomodulatory agents like methotrexate and colchicine, are being explored. Understanding HIV-driven immune dysregulation may lead to novel strategies to mitigate cardiovascular risk in this population."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Hematological Disorders • Human Immunodeficiency Virus • Infectious Disease • Inflammation • APOA1 • CASP1 • CD14 • CRP • IL10 • IL1B • IL6

LEADS - a comprehensive human liver-on-a-chip for non-alcoholic steatohepatitis (NASH) drug testing. (PubMed, Lab Chip) - "Notably, treatment with saroglitazar, pioglitazone, cenicriviroc (CVC), obeticholic acid (OCA) and resmetirom produced responses similar to those observed in clinical trials. Taken together, our LEADS model is the first model developed using patient-derived hepatic stem cells which recapitulated all key features used for comprehensive drug testing, with results matching to clinical responses."

Journal • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Oncology • Solid Tumor

SARS-CoV-2 N protein and anti-spike serologies: insights into COVID-19 disease severity and mortality-a secondary analysis of the ACTIV-1 trial. (PubMed, Ther Adv Infect Dis) - "N protein levels could provide insights into COVID-19 disease progression and prognosis. Further research is needed to explore the clinical implications of these findings to optimize patient care and enhance outcomes."

Clinical • Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Resource Use in the Randomized Master Protocol for Immune Modulators for Treating COVID-19 (ACTIV-1 IM): A Secondary Data Analysis. (PubMed, CHEST Crit Care) - P3 | "Examine if a single dose of infliximab or abatacept, in addition to remdesivir and steroids, decreased resource utilization among participants hospitalized with COVID-19 pneumonia. Accelerating COVID-19 Therapeutic Interventions and Vaccines Immunomodulator (ACTIV-1 IM) master protocol was a randomized, placebo-controlled trial examining the potential benefit in time to recovery and mortality of immunomodulators infliximab, abatacept, and cenicriviroc...Infliximab and abatacept use were associated with decreased use of healthcare resources over 28 days compared to placebo, but the absolute differences were small. www.clinicaltrials.gov (NCT04593940)."

Journal • Critical care • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Effects of anti-inflammatory drugs on distinct endotypes of chronic rhinosinusitis without nasal polyps: comparison using an ex-vivo model. (PubMed, Eur Rev Med Pharmacol Sci) - "Medications used to treat CRS may have different effects on distinct CRS endotypes."

Clinical • Journal • Preclinical • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis • CCL4 • IFNG • IL17A • IL5 • RETN

Evaluating the Impact of Cenicriviroc in Metabolic Dysfunction-Associated Steatohepatitis (MASH): A Systematic Review (ACG 2024) - "Three trials, including 2234 patients, were reviewed. Two studies were randomized control trials and one an open label rollover. The mean age and BMI of all participants was 55.49 ± 10.72 and 35.07 ± 6.87 kg/m², respectively."

Review • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

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

CCL2-CCR2 AXIS INHIBITION REDUCES LIVER FIBROSIS BY RESTORING THE IMMUNE CELL LANDSCAPE (AASLD 2024) - "Cenicriviroc (CVC) was administrated to fibrotic mice in prevention and treatment models... In summary, activation of the angiocrine signal CCL2 in injured LSECs recruits CCR2+ monocyte-derived macrophages to the liver, leading to liver fibrosis. CVC restores the hepatic immune cell landscape by inhibiting profibrotic gene transcription via the CCR2-STAT1/NFκB/ERK signaling pathways."

Immune cell • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • CCL2 • CCR2 • Fascin • FSCN1 • IL1B • XAF1

TREATMENT WITH THE CCR2/CCR5 ANTAGONIST CENICRIVIROC DOES NOT AFFECT MASH AND FIBROSIS DEVELOPMENT IN LDLR-/-.LEIDEN MICE, TRANSLATIONAL TO CLINICAL PHASE 3 TRIALRESULTS (AASLD 2024) - "While many preclinical models have shown efficacy of CVC that contrasts clinical observations, CVC treatment (at a translational dose that did show efficacy in other preclinical models) in the HFD-fed Ldlr-/-.Leiden mouse did not reduce hepatic fibrosis – in line with the outcome of the phase 3 AURORA trial. These findings underline the importance for validation of preclinical MASH models not only with treatments that have been found to have clinical efficacy, but also with treatments that have failed clinically."

P3 data • Preclinical • Dyslipidemia • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • CCR2 • TIMP1

Pipeline of New Drug Treatment for Non-alcoholic Fatty Liver Disease/Metabolic Dysfunction-associated Steatotic Liver Disease. (PubMed, J Clin Transl Hepatol) - "Agents in this group include peroxisome proliferator-activated receptor agonists (e.g., pioglitazone, elafibranor, saroglitazar), bile acid-farnesoid X receptor axis regulators (obeticholic acid), de novo lipogenesis inhibitors (aramchol, NDI-010976), and fibroblast growth factor 21/19 analogs...Agents in this group include antioxidants (vitamin E), tumor necrosis factor α pathway regulators (emricasan, pentoxifylline, ZSP1601), and immune modulators (cenicriviroc, belapectin). The final group targets the gut (IMM-124e, solithromycin). Combination therapies targeting different pathogenetic pathways may provide an alternative to MASLD treatment with higher efficacy and fewer side effects. This review aimed to provide an update on these medications."

Journal • Review • Diabetes • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Type 2 Diabetes Mellitus • FGF21 • TNFA

CCL2-CCR2 axis inhibition reduces liver fibrosis by restoring the immune cell landscape (IDDF 2024) - "Cenicriviroc (CVC) was administrated to fibrotic mice in prevention and treatment models... In summary, activation of the angiocrine signal CCL2 in injured LSECs recruits CCR2+ monocyte-derived macrophages to the liver, leading to liver fibrosis. CVC restores the hepatic immune cell landscape by inhibiting profibrotic gene transcription via the CCR2-STAT1/NFkB/ERK signaling pathways."

Immune cell • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • CCL2 • CCR2 • Fascin • FSCN1 • IL1B • XAF1

Current strategies for nonalcoholic fatty liver disease treatment (Review). (PubMed, Int J Mol Med) - "The present review summarized the methods and mechanisms to treat NAFLD, including the Mediterranean diet, physical activity and exercise, bariatric surgery and specific therapeutic agents, including statins, peroxisome proliferator‑activated receptor agonists, cenicriviroc and farnesoid X receptor agonists...Considering their different mechanisms of action, combining some of them may prove an efficacious treatment for NAFLD. In this light, the present review describes recent progress and future prospects in treating NAFLD."

Journal • Review • Hepatology • Inflammation • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Current status of the small molecule anti-HIV drugs in the pipeline or recently approved. (PubMed, Bioorg Med Chem) - "These compounds include analogues of nucleoside reverse transcriptase inhibitors (NRTIs) - islatravir and censavudine; non-nucleoside reverse transcriptase inhibitors (NNRTIs) - Rilpivirine, elsulfavirine and doravirine; integrase inhibitors namely cabotegravir and dolutegravir and chemokine coreceptors 5 and 2 (CC5/CCR2) antagonists for example cenicriviroc. Also, fostemsavir is being developed as an attachment inhibitor while lenacapavir, VH4004280 and VH4011499 are capsid inhibitors. Others are maturation inhibitors such as GSK-254, GSK3532795, GSK3739937, GSK2838232, and other compounds labelled as miscellaneous (do not belong to the classical groups of anti-HIV drugs or to the newer classes) such as obefazimod and BIT225. There is a considerable progress in the development of new anti-HIV drugs and the effort will continue since HIV infections has no cure or vaccine till now. Efforts are needed to reduce the toxicity of available drugs or discover new drugs with new..."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease • CCR2

Inhibition of intrahepatic monocyte recruitment by Cenicriviroc and extracellular matrix degradation by MMP1 synergistically attenuate liver inflammation and fibrogenesis in vivo. (PubMed, Sci Rep) - "MMP1 + CVC also ameliorated liver fibrogenesis via inhibiting HSCs activation as assessed by collagen-I staining and collagen-I and α-SMA mRNA expression. In conclusion, we demonstrated that a combination therapeutic approach by combining CVC and MMP1 to inhibit intrahepatic monocyte recruitment and increasing collagen degradation respectively ameliorate liver inflammation and fibrosis."

Journal • Preclinical • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Liver Failure • CCL2 • CCR2 • ITGAM • MMP1 • TGFB1 • TNFA

Efficacy of Infliximab, Abatacept, and Cenicriviroc for the Treatment of Adults Hospitalized with COVID-19 Pneumonia. (PubMed, Int J Infect Dis) - "There was also evidence for the benefit of abatacept. There was no evidence for the benefit of cenicriviroc."

Clinical • Journal • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Innate immune memory after brain injury drives inflammatory cardiac dysfunction. (PubMed, Cell) - "By neutralizing post-stroke IL-1β or blocking pro-inflammatory monocyte trafficking with a CCR2/5 inhibitor, we prevented post-stroke cardiac dysfunction. Such immune-targeted therapies could potentially prevent various IL-1β-mediated comorbidities, offering a framework for secondary prevention immunotherapy."

Journal • Cardiovascular • CNS Disorders • Fibrosis • Immunology • Inflammation • Transplantation • Vascular Neurology • CCR2 • IL1B

A New Application for Cenicriviroc, a Dual CCR2/CCR5 Antagonist, in the Treatment of Painful Diabetic Neuropathy in a Mouse Model. (PubMed, Int J Mol Sci) - "Moreover, repeated coadministration of cenicriviroc with morphine delays the development of opioid tolerance, while the best and longest-lasting analgesic effect is achieved by repeated administration of cenicriviroc alone, which reduces pain hypersensitivity in STZ-exposed mice, and unlike morphine, no tolerance to the analgesic effects of CVC is observed until Day 15 of treatment. Based on these results, we suggest that targeting CCR2 and CCR5 with CVC is a potent therapeutic option for novel pain treatments in diabetic neuropathy patients."

Journal • Preclinical • Diabetes • Diabetic Neuropathy • Immunology • Metabolic Disorders • Neuralgia • Pain • CCL2 • CCL8 • CCR2

Identification of ibuprofen targeting CXCR family members to alleviate metabolic disturbance in lipodystrophy based on bioinformatics and in vivo experimental verification. (PubMed, Front Endocrinol (Lausanne)) - "Eventually, the drug-gene network included ibuprofen-CXCR1, ibuprofen-CXCR1, cenicriviroc-CCR2, fenofibrate-JUN, and other relationship pairs. Ibuprofen treatment was also validated to downregulate CXCR1 and CXCR2 in peripheral blood mononuclear cells (PBMCs) and improve glucose tolerance, hypertriglyceridemia, hepatic steatosis, and liver inflammation in lipodystrophy mice. Eight biomarkers, namely, CXCR2, TNFSF10, NLRC4, CCR2, CEACAM3, TLR10, TNFAIP3, and JUN, were identified through bioinformatic analyses, and ibuprofen targeting CXCR1 and CXCR2 in PBMCs was shown to improve metabolic disturbance in lipodystrophy, contributing to studies related to the diagnosis and treatment of lipodystrophy."

Biomarker • Journal • Preclinical • Diabetes • Dyslipidemia • Hepatology • Hypertriglyceridemia • Inflammation • Lipodystrophy • Metabolic Disorders • Rare Diseases • CCR2 • CXCR1 • CXCR2 • TLR1 • TNFAIP3 • TNFSF10

A Study to Evaluate the Effects of Cenicriviroc Mesylate on Arterial Inflammation in People Living With HIV (clinicaltrials.gov) - P2 | N=110 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease • Inflammation • CD4 • CRP

Cenicriviroc suppresses and reverses steatohepatitis by regulating macrophage infiltration and M2 polarization in mice. (PubMed, Endocrinology) - "Lastly, CVC reversed insulin resistance as well as steatosis, inflammation, and fibrosis of the liver in mice with pre-existing NASH. In conclusion CVC prevented and reversed hepatic steatosis, insulin resistance, inflammation, and fibrogenesis in the livers of NASH mice via M2 macrophage polarization."

Journal • Preclinical • Fibrosis • Hepatitis B • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • CCR2 • IL4

Treatment with the CCR2/CCR5 antagonist Cenicriviroc does not affect MASH and fibrosis development in Ldlr-/-.Leiden mice, translational to clinical phase 3 trial results (EASL-ILC 2024) - "While many preclinical models have shown efficacy of CVC that contrasts clinical observations, CVC treatment (at a translational dose that did show efficacy in other preclinical models) in the HFD-fed Ldlr-/-.Leiden mouse did not reduce hepatic fibrosis – in line with the outcome of the phase 3 AURORA trial. These findings underline the importance for validation of preclinical MASH models not only with treatments that have been found to have clinical efficacy, but also with treatments that have failed clinically."

P3 data • Preclinical • Dyslipidemia • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • CCR2 • TIMP1

Fatty liver disease: time to target CCR5? (PubMed, Expert Opin Ther Targets) - No abstract available

Journal • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

CCR2/CCR5 antagonist cenicriviroc reduces colonic inflammation and fibrosis in experimental colitis. (PubMed, J Gastroenterol Hepatol) - "CVC significantly inhibited inflammation through CCL5/CCR5 signaling without damaging vital organs and suppressed fibrotic activation in chronic colitis, suggesting its great potential to relieve colonic inflammation and fibrosis."

Journal • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • CCL2 • CCL5 • CCR2 • CTGF • CX3CL1 • MMP9 • TGFB1 • TNFA