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

CCR2/CCR5 Signaling Defines a Pathogenic Interstitial Macrophage Subset That Drives Severe Asthma. (PubMed, Clin Transl Allergy) - "Lyve1loMHCIIhi IMs orchestrate airway inflammation in severe asthma. Dual CCR2/CCR5 antagonism inhibits their recruitment, restores macrophage balance, and halts disease progression, highlighting this pathway as a promising therapeutic target."

Journal • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CCR2 • CCR5

Dual CCR2/CCR5 Antagonism with Cenicriviroc Alleviates Nerve Injury-Induced Hypersensitivity and Prevents Morphine Tolerancevia Modulation of Neuroimmune Signaling. (PubMed, Cell Mol Neurobiol) - "Furthermore, on Day 8, cenicriviroc increased the level of Akt/STAT3, and decreased pp38/pERK and pronociceptive CCL2/3/5. The obtained results indicate that simultaneous targeting of CCR2/5 by cenicriviroc may have great potential for neuropathic pain therapies, especially since the drug is already in clinical trials for other conditions."

Journal • Immunology • Neuralgia • Pain • CCL2 • CCR2 • IL10 • IL1B • STAT3 • TNFA

Shared immune-inflammatory gene networks and drug prediction in polycystic ovary syndrome and type 2 diabetes mellitus: a bioinformatics and experimental validation study. (PubMed, Front Endocrinol (Lausanne)) - "Moreover, maraviroc, cenicriviroc, PF-04634817 (targeting CCR5), butein (targeting ITGB2), dimethyl sulfoxide (targeting ITGAM), and rovelizumab (targeting both ITGB2 and ITGAM) are potential therapeutic drugs. However, these findings require validation through further clinical and experimental studies."

Journal • Diabetes • Infectious Disease • Inflammation • Metabolic Disorders • Pertussis • Polycystic Ovary Syndrome • Respiratory Diseases • Type 2 Diabetes Mellitus • AIF1 • C1QB • IRF8 • ITGAM • ITGB2 • SPI1

The central role of macrophages in skeletal muscle regeneration: Phenotypic Polarization, metabolic reprogramming, and therapeutic prospects. (PubMed, Biochem Pharmacol) - "A key feature is the integration of molecular docking analyses, revealing structural interactions between compounds (e.g., AICAR, Cenicriviroc) and targets like AMPK, PPARγ, CCR2, and CCR5. This provides a structural pharmacology foundation for developing targeted immunometabolic therapies to restore muscle regeneration in injury and degenerative diseases."

Journal • Review • Duchenne Muscular Dystrophy • Fibrosis • Genetic Disorders • Immunology • Inflammation • Muscular Dystrophy • AMPK • CCR2

I-SPY_COVID: I-SPY COVID-19 TRIAL: An Adaptive Platform Trial for Critically Ill Patients (clinicaltrials.gov) - P2 | N=1500 | Active, not recruiting | Sponsor: QuantumLeap Healthcare Collaborative | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Novel Coronavirus Disease

CCR2/CCR5 antagonism with cenicriviroc relieves neuropathic pain induced by sciatic nerve injury and delays morphine tolerance in mice. (PubMed, Biochem Pharmacol) - "Cenicriviroc exerts sustained analgesia by simultaneously blocking CCR2 and CCR5 - particularly CCR2 signaling in neurons and glia - which appears to be key to its efficacy. These findings highlight cenicriviroc as a promising, translational candidate for neuropathic pain therapy."

Journal • Preclinical • Immunology • Neuralgia • Pain • CCR2 • FAP • GFAP

A Randomized, Multi-Center, Double-Blind, Placebo-Controlled ACTG Study to Evaluate the Effects of Cenicriviroc on Arterial Inflammation in People with HIV (EACS 2025) - "As expected, the CCR2 ligand MCP-1 increased 4.7-fold and the CCR5 ligand MIP-1β increased 1.65-fold with CVC compared to placebo (p<0.001 for both). Conclusions : In a rigorous RCT with good participant retention and adherence, when compared to placebo, blockade of CCR2 and CCR5 with cenicriviroc for 24 weeks did not reduce imaging markers of arterial inflammation or circulating biomarkers of inflammation in people with ART-controlled HIV."

Clinical • Human Immunodeficiency Virus • Infectious Disease • CCL4 • CCR2 • CRP • IL6

Chemokine receptor type-5: a key regulator of immunity, disease pathogenesis, and emerging therapeutic target. (PubMed, Inflammopharmacology) - "With therapeutic inhibition of CCR5 gaining attention, Maraviroc is approved for HIV treatment, while monoclonal antibodies such as leronlimab, genetic strategies (CRISPR), and dual CCR2/CCR5 antagonists such as cenicriviroc are under investigation for broader applications. Blocking CCR5 has shown efficacy in reducing metastasis and improving chemotherapy outcomes, reinforcing its therapeutic potential. Along with CCR5's role in disease pathogenesis, emphasizing its involvement in immune regulation and inflammatory processes, this review explores the multifaceted role of CCR5 in immunity, its contribution to disease pathogenesis, and innovative therapeutic interventions targeting CCR5 to modulate immune responses and treat diseases."

Journal • Review • Atherosclerosis • Breast Cancer • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • HER2 Breast Cancer • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammatory Arthritis • Inflammatory Bowel Disease • Oncology • Rheumatoid Arthritis • Rheumatology • Solid Tumor • CCL3 • CCR2 • CCR5 • HER-2

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