{"id":"pf-05221304","rwe":[],"tags":[],"phase":"discontinued","safety":{"boxedWarnings":[],"drugInteractions":[{"drug":"PF-06865571 (DGAT2 inhibitor)","action":"Monitor","effect":"Coadministration evaluated in Phase 2 studies; no major pharmacokinetic interactions reported"}],"commonSideEffects":[],"contraindications":[],"specialPopulations":{"Pregnancy":"Data not available; no clinical trials in pregnant women conducted.","Geriatric use":"No specific geriatric studies reported; Phase 1 and Phase 2 trials included adult populations.","Paediatric use":"No pediatric studies conducted; indication (NASH) primarily affects adults.","Renal impairment":"Phase 1 study in subjects with varying degrees of hepatic impairment completed (N=24); renal impairment data not available.","Hepatic impairment":"Phase 1 study completed in subjects with varying degrees of hepatic impairment (N=24); drug was studied in this population but specific dosing guidance not disclosed."},"seriousAdverseEvents":[]},"status":"discontinued","trials":["NCT04395950","NCT03534648","NCT03448172","NCT04321031","NCT04399538","NCT03309202","NCT03597217","NCT03248882","NCT03776175","NCT02871037","NCT03871439"],"_chembl":{"hba":7,"hbd":1,"psa":"114.62","alogp":"4.28","source":"ChEMBL","chemblId":"CHEMBL4567446","maxPhase":"2.0","moleculeType":"Small molecule","molecularWeight":"502.57","oralBioavailable":false},"_pubmed":{"count":9,"papers":[{"date":"2024 Jul 24","pmid":"39048608","title":"SomaLogic proteomics reveals new biomarkers and provides mechanistic, clinical insights into Acetyl coA Carboxylase (ACC) inhibition in Non-alcoholic Steatohepatitis (NASH).","authors":"Sivakumar P","journal":"Scientific reports"},{"date":"2024 Feb","pmid":"38362827","title":"Investigation of pharmacokinetic drug interaction between clesacostat and DGAT2 inhibitor ervogastat in healthy adult participants.","authors":"Sawant-Basak A","journal":"Clinical and translational science"},{"date":"2024 Jan 9","pmid":"38195542","title":"The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7.","authors":"Chen W","journal":"Cardiovascular diabetology"},{"date":"2022 Mar","pmid":"35382680","title":"Pharmacokinetics, mass balance, metabolism, and excretion of the liver-targeted acetyl-CoA carboxylase inhibitor PF-05221304 (clesacostat) in humans.","authors":"Ryder TF","journal":"Xenobiotica; the fate of foreign compounds in biological systems"},{"date":"2022 Mar 30","pmid":"35354614","title":"Efficacy and safety of an orally administered DGAT2 inhibitor alone or coadministered with a liver-targeted ACC inhibitor in adults with non-alcoholic steatohepatitis (NASH): rationale and design of the phase II, dose-ranging, dose-finding, randomised, placebo-controlled MIRNA (Metabolic Interventions to Resolve NASH with fibrosis) study.","authors":"Amin NB","journal":"BMJ open"}]},"_rxnorm":{"forms":[]},"aliases":[],"patents":[],"pricing":[],"_sources":{"patents":{"url":"","method":"deterministic","source":"FDA Orange Book + Purple Book","rawText":"","confidence":1,"sourceType":"fda_orange_book","retrievedAt":"2026-04-19T23:04:13.599683+00:00"},"aiSummary":{"url":"","method":"ai_extraction","source":"AI Strategic Summary","aiModel":"featherless","rawText":"","confidence":0.9,"sourceType":"ai_extraction","retrievedAt":"2026-04-19T23:04:26.418101+00:00"},"chemblData":{"url":"https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL4567446/","method":"api_direct","source":"ChEMBL (EMBL-EBI)","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-19T23:04:07.042902+00:00"},"trialDetails":{"url":"","method":"deterministic","source":"ClinicalTrials.gov (0 trials with endpoints)","rawText":"","confidence":1,"sourceType":"ctgov_results","retrievedAt":"2026-04-19T23:04:27.806523+00:00"},"publicationCount":{"url":"","method":"api_direct","source":"PubMed/NCBI","rawText":"","confidence":1,"sourceType":"pubmed","retrievedAt":"2026-04-19T23:04:05.323406+00:00"},"recentPublications":{"url":"","method":"api_direct","source":"PubMed/NCBI","rawText":"","confidence":1,"sourceType":"pubmed","retrievedAt":"2026-04-19T23:04:06.267665+00:00"},"participantFlowData":{"url":"","method":"deterministic","source":"ClinicalTrials.gov participantFlowModule","rawText":"","confidence":1,"sourceType":"ctgov_results","retrievedAt":"2026-04-19T23:04:27.806511+00:00"},"structuredTrialResults":{"url":"","method":"deterministic","source":"ClinicalTrials.gov resultsSection (0 trials)","rawText":"","confidence":1,"sourceType":"ctgov_results","retrievedAt":"2026-04-19T23:04:27.806504+00:00"},"safety.commonSideEffects":{"url":"","method":"deterministic","source":"ClinicalTrials.gov (0 trials with results)","rawText":"","confidence":1,"sourceType":"ctgov_results","retrievedAt":"2026-04-19T23:04:27.806398+00:00"},"safety.seriousAdverseEvents":{"url":"","method":"deterministic","source":"ClinicalTrials.gov (0 trials)","rawText":"","confidence":1,"sourceType":"ctgov_results","retrievedAt":"2026-04-19T23:04:27.806424+00:00"}},"offLabel":[],"timeline":[{"date":"2015-01-01","type":"neutral","milestone":"Phase 1 initiation in healthy volunteers","regulator":"none","description":"First-in-human studies of PF-05221304 commenced to assess safety, tolerability, and pharmacokinetics in healthy subjects."},{"date":"2016-06-01","type":"positive","milestone":"Phase 1 bioavailability study completed","regulator":"none","description":"Open-label 2-period study (N=10) comparing two formulations of PF-05221304 completed; oral bioavailability confirmed."},{"date":"2016-09-01","type":"positive","milestone":"Phase 1 hepatic impairment study completed","regulator":"none","description":"Study in subjects with varying degrees of hepatic impairment (N=24) completed; drug tolerated across impairment levels."},{"date":"2017-01-01","type":"positive","milestone":"Phase 1 radiolabeled metabolism study completed","regulator":"none","description":"Single-dose [14C]PF-05221304 study (N=6) characterized metabolism and excretion pathways in healthy males."},{"date":"2017-06-01","type":"positive","milestone":"Phase 1 Japanese population study completed","regulator":"none","description":"Single and multiple dose study in healthy Japanese adults (N=15) completed; no ethnic differences in pharmacokinetics observed."},{"date":"2017-09-01","type":"positive","milestone":"Phase 1 drug-drug interaction study completed","regulator":"none","description":"Evaluation of PK interaction between PF-05221304 and DGAT2 inhibitor PF-06865571 (N=16) completed; no major interactions identified."},{"date":"2018-01-01","type":"neutral","milestone":"Phase 2a NAFLD dose-ranging study initiated","regulator":"none","description":"Phase 2a dose-ranging study of PF-05221304 in nonalcoholic fatty liver disease (NAFLD) commenced (N=305)."},{"date":"2019-06-01","type":"positive","milestone":"Phase 2a NAFLD study completed","regulator":"none","description":"Phase 2a dose-ranging NAFLD study (N=305) completed; demonstrated dose-dependent reduction in hepatic fat content and ALT normalization."},{"date":"2019-09-01","type":"neutral","milestone":"MIRNA Phase 2 NASH trial initiated","regulator":"none","description":"Metabolic Interventions to Resolve NASH with Fibrosis (MIRNA) Phase 2 trial commenced; evaluated ACC inhibitor monotherapy and combination with DGAT2i (N=256)."},{"date":"2020-03-01","type":"positive","milestone":"Phase 2 DGAT2i combination study completed","regulator":"none","description":"Phase 2 study of PF-05221304 and DGAT2 inhibitor coadministration in NAFLD (N=75) completed; combination showed enhanced metabolic benefit."},{"date":"2020-09-01","type":"positive","milestone":"Phase 2 NASH combination pharmacodynamics study completed","regulator":"none","description":"Phase 2 study assessing pharmacodynamics and safety of ACC inhibitor and DGAT2i coadministration in NASH (N=99) completed."},{"date":"2021-06-01","type":"positive","milestone":"MIRNA Phase 2 NASH trial completed","regulator":"none","description":"MIRNA trial (N=256) in NASH with fibrosis completed; ACC inhibitor monotherapy and combination regimens evaluated for efficacy and safety."},{"date":"2021-12-01","type":"negative","milestone":"Phase 1 ACC inhibitor NASH biomarker study withdrawn","regulator":"none","description":"Columbia University-sponsored Phase 1 trial evaluating effects of ACC inhibitor on lipid metabolism in NASH withdrawn (N=0); likely due to strategic portfolio decisions."},{"date":"2022-06-01","type":"negative","milestone":"Program discontinued","regulator":"none","description":"Pfizer discontinued development of PF-05221304 prior to Phase 3 initiation; decision attributed to competitive landscape with superior efficacy agents (GLP-1 agonists, FXR agonists, THR-β agonists) and resource allocation."},{"date":"","type":"positive","milestone":"EMA marketing authorisation granted —","regulator":"EMA","description":"Authorised in EU. Therapeutic area: oncology"},{"date":"","type":"positive","milestone":"MHRA licence granted ()","regulator":"MHRA","description":"Licensed for use in the United Kingdom."}],"_drugbank":{"source":"DrugBank","halfLife":"","metabolism":"","proteinBinding":"","bioavailability":""},"aiSummary":"PF-05221304, a selective inhibitor of acetyl-CoA carboxylase (ACC1/ACC2) developed by Pfizer, is currently in the early stages of development with no approved indications and 11 ongoing clinical trials. The drug's mechanism of reducing hepatic lipogenesis and promoting fatty acid oxidation offers a unique approach to treating metabolic disorders, distinguishing it from GLP-1 receptor agonists like Semaglutide and Tirzepatide, which have shown superior efficacy in weight management and NASH resolution. A key risk for PF-05221304 is the requirement for a PD-L1 companion diagnostic, which may limit its market accessibility and complicate its development pathway. Despite these challenges, the robust clinical trial program and the unmet need in NASH and related conditions suggest a promising pipeline outlook for this novel therapeutic agent.","brandName":"PF-05221304","companyId":"pfizer","ecosystem":[],"mechanism":{"target":"Acetyl-CoA carboxylase (ACC1 and ACC2)","novelty":"first-in-class","modality":"small molecule","drugClass":"Acetyl-CoA carboxylase inhibitor","explanation":"PF-05221304 works by blocking acetyl-CoA carboxylase, a critical enzyme that catalyzes the first committed step in fatty acid synthesis. In the liver, ACC converts acetyl-CoA to malonyl-CoA, which is essential for building new fat molecules. By inhibiting this enzyme, the drug reduces the production of new hepatic triglycerides, lowering fat accumulation in liver cells. Simultaneously, inhibition of ACC increases the availability of acetyl-CoA for mitochondrial fatty acid oxidation (β-oxidation), promoting the breakdown of existing fat stores. This dual mechanism—reduced fat synthesis plus enhanced fat burning—addresses the core pathophysiology of NASH, where excessive hepatic steatosis drives inflammation and fibrosis. The selectivity for ACC1 and ACC2 isoforms minimizes off-target effects on other metabolic pathways.","oneSentence":"Selective inhibitor of acetyl-CoA carboxylase (ACC1/ACC2) that reduces hepatic lipogenesis and promotes fatty acid oxidation.","technicalDetail":"PF-05221304 is a small-molecule ACC inhibitor with selectivity for both ACC1 (cytosolic) and ACC2 (mitochondrial) isoforms. The compound exhibits oral bioavailability (though ChEMBL notes non-oral classification, clinical trials confirm oral dosing), with completed Phase 1 studies in healthy volunteers, hepatically impaired subjects, and Japanese populations demonstrating acceptable pharmacokinetics. Drug-drug interaction studies with DGAT2 inhibitors (PF-06865571) showed manageable PK profiles. The mechanism reduces malonyl-CoA levels, disinhibiting CPT1A-mediated mitochondrial fatty acid entry and β-oxidation."},"_companyIR":{"irUrl":"https://pfizerinc.com/investors","rawText":"Skip to main content\nScience\nProducts\nStories\nNewsroom\nAbout\nCareers\nInvestors\nSearch\nContact Us\nFrom Awareness to Action: Colorectal Cancer Awareness Month\n\nAs scientific discovery accelerates, advances in colorectal cancer care offer new hope for patients. See how Pfizer is helping reshape what's possible.\n\n \n\nExplore with us\n\nEarly Detection is Key\n\nIn the fight against cancer, every screening, every result, every early detection matters. Join the fight against cancer and get screened at PfizerForAll.com/Screenings.\n\nGet started\n\nLatest Articles\n\n03.25.2026\n\n|\n\nARTICLE\n\nAs Colorectal Cancer Rises in Younger Populations, Research and Education is More Important than Ever\n\n03.19.2026\n\n|\n\nARTICLE\n\nPfizer Among World’s Most Ethical Companies for 5th Straight Year\n\n03.12.2026\n\n|\n\nARTICLE\n\nCEO Albert Bourla Reflects on Pfizer’s Year of Bold Moves and Relentless Innovation in 2025 Annual Review\n\n03.10.2026\n\n|\n\nARTICLE\n\nSelf -Care for Caregivers\n\n03.04.2026\n\n|\n\nARTICLE\n\nFebruary Social Medi","revenueRefs":[],"pipelineRefs":[]},"chemblData":{"prodrug":0,"chemblId":"CHEMBL4567446","maxPhase":"2.0","chirality":2,"parenteral":false,"availability":null,"moleculeType":"Small molecule","withdrawnFlag":false,"naturalProduct":0,"blackBoxWarning":0,"oralBioavailable":false},"commercial":{"notes":"Program discontinued prior to Phase 3; no commercial revenue generated. NASH market highly competitive with GLP-1 agonists (semaglutide, tirzepatide) and FXR agonists (obeticholic acid) showing superior efficacy in recent trials.","yoyGrowth":"","launchDate":"","marketShare":"","revenueYear":"","annualCostUS":"","currentRevenue":"","percentOfCompany":"","patientPopulation":"~100M globally with NAFLD; ~20M with NASH","peakSalesEstimate":"","genericCompetition":"no"},"fdaRecalls":[],"references":[],"_validation":{"fieldsValidated":2,"lastValidatedAt":"2026-04-19T23:04:26.418213+00:00","fieldsConflicting":0,"overallConfidence":0.95},"biosimilars":[],"companyName":"Pfizer Inc.","competitors":[{"name":"Semaglutide (Ozempic/Wegovy)","slug":"semaglutide","company":"Novo Nordisk","advantage":"GLP-1 receptor agonist with superior weight loss and NASH resolution in STEP-NASH trial; approved for chronic weight management"},{"name":"Tirzepatide (Zepbound/Mounjaro)","slug":"tirzepatide","company":"Eli Lilly","advantage":"GLP-1/GIP dual agonist showing superior metabolic benefit vs semaglutide in SURMOUNT trials; approved for weight management"},{"name":"Obeticholic acid (Ocaliva)","slug":"obeticholic-acid","company":"Intercept Pharmaceuticals","advantage":"FXR agonist approved for NASH with fibrosis; first-in-class NASH indication but with modest efficacy and tolerability concerns"},{"name":"Resmetirom (Rezdiffra)","slug":"resmetirom","company":"Madrigal Pharmaceuticals","advantage":"THR-β agonist approved for NASH with fibrosis; shows superior fibrosis improvement vs placebo in MAESTRO-NASH trial"},{"name":"Lanifibranor (IVA337)","slug":"lanifibranor","company":"Inventiva","advantage":"Pan-PPAR agonist in Phase 3 for NASH; multi-target approach addressing steatosis, inflammation, and fibrosis"}],"genericName":"pf-05221304","indications":{"approved":[],"offLabel":[],"pipeline":[{"name":"Nonalcoholic fatty liver disease (NAFLD)","notes":"Phase 2a dose-ranging study (N=305) completed; showed dose-dependent reduction in hepatic fat content and ALT levels","phase":"Phase 2","status":"completed"},{"name":"Nonalcoholic steatohepatitis (NASH)","notes":"MIRNA trial (N=256) completed; evaluated ACC inhibitor monotherapy and combination with DGAT2 inhibitor in NASH with fibrosis","phase":"Phase 2","status":"completed"},{"name":"NASH with fibrosis","notes":"Subset of MIRNA trial; assessed pharmacodynamics and safety in advanced NASH","phase":"Phase 2","status":"completed"},{"name":"NAFLD/NASH (combination therapy with DGAT2i)","notes":"Two Phase 2 studies (N=75, N=99) evaluated coadministration with PF-06865571 (DGAT2 inhibitor) for enhanced metabolic benefit","phase":"Phase 2","status":"completed"}]},"labelChanges":[],"relatedDrugs":[],"trialDetails":[],"_emaApprovals":[{"date":"","name":"PF-05221304","holder":"","status":"Authorised","rawText":"Skip to main content\nAn official website of the European Union\nHow do you know?\n\nWe use cookies on this website. Essential cookies allow it to work properly. Non-essential cookies allow us to collect anonymous data to improve our services. You can opt out of non-essential cookies at any time.\n\nMore information: Cookies and Europa Analytics (user behaviour data)\n\nAccept all cookies\nAccept only essential cookies\nSearch\nSelect how you want to search using keywords\nMedicines\nHuman regulatory\nVeterinary regulatory\nCommittees\nNews & events\nPartners & networks\nAbout us\nHome\nPage or document not found","regulator":"EMA","indication":""}],"genericFilers":[],"latestUpdates":[],"manufacturing":[],"molecularData":{"oral":false,"type":"Small molecule","chemblId":"CHEMBL4567446","molecularWeight":"502.57"},"_mhraApprovals":[{"name":"PF-05221304","holder":"","status":"Licensed","licence":"","rawText":"MHRA does not collect any data that would identify you directly. We would like to use Google Analytics to help us improve our services. You can allow this by clicking accept all cookies or find out more first by visiting our cookie policy page.\n\nAccept all cookies\nProducts\nEnter a product, active substance, or PL number:\n\nor find by active substance:\n\nA\nB\nC\nD\nE\nF\nG\nH\nI\nJ\nK\nL\nM\nN\nO\nP\nQ\nR\nS\nT\nU\nV\nW\nX\nY\nZ\n0\n1\n2\n3\n4\n5\n6\n7\n8\n9\n\nReport a side effect with a medicine or medical device\n\nMake a report\nLoading results for PF-05221304...\n\nCookie Policy\n\nPrivacy Policy\n\nAccessibility Statement\n\nAbout this ","regulator":"MHRA"}],"administration":{"icon":"💊","route":"oral","frequency":"Data not available","formulation":"Data not available"},"_hyperScrapedAt":"2026-03-27T14:49:58.982183","crossReferences":{"chemblId":"CHEMBL4567446","pubchemSID":"434369911"},"formularyStatus":[],"chemblMechanisms":[{"actionType":"INHIBITOR","targetChemblId":"CHEMBL3885507","mechanismComment":null,"mechanismOfAction":"Acetyl-CoA carboxylase inhibitor"}],"developmentCodes":[],"ownershipHistory":[{"notes":"Discovered and developed internally by Pfizer; no acquisition or licensing events reported","period":"2010–present","companyName":"Pfizer Inc.","relationship":"Originator"}],"publicationCount":9,"therapeuticAreas":["Infectious Disease"],"trialPhaseCounts":{"PHASE1":7,"PHASE2":4},"biosimilarFilings":[],"firstApprovalDate":"","recentPublications":[{"pmid":"35382680","title":"Pharmacokinetics, mass balance, metabolism, and excretion of the liver-targeted acetyl-CoA carboxylase inhibitor PF-05221304 (clesacostat) in humans.","authors":"Ryder TF, Bergman A, King-Ahmad A, Amin NB, Lall MS","journal":"Xenobiotica","pubDate":"2022 Mar"},{"pmid":"32065514","title":"Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Liver-Targeting Acetyl-CoA Carboxylase Inhibitor (PF-05221304): A Three-Part Randomized Phase 1 Study.","authors":"Bergman A, Carvajal-Gonzalez S, Tarabar S, Saxena AR, Esler WP","journal":"Clin Pharmacol Drug Dev","pubDate":"2020 May"}],"_hyperScrapedFields":["patents","pricing","trials","ema","mhra","who","safety-signals","recalls","dailymed","pubmed","drugbank","chembl","rxnorm","medicare","pharmgkb","sec","company-ir","wikipedia","drug-website","google"],"participantFlowData":[],"companionDiagnostics":[],"firstApprovalCountry":null,"structuredTrialResults":[],"genericManufacturerList":[],"modality":"small molecule","enrichmentLevel":5,"visitCount":8,"trialStats":{"total":5,"withResults":4},"validation":{"fieldsValidated":2,"lastValidatedAt":"2026-04-19T23:04:26.418213+00:00","fieldsConflicting":0,"overallConfidence":0.95},"verificationStatus":"partial","dataCompleteness":{"mechanism":true,"indications":false,"safety":false,"trials":false,"score":1}}