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PTJA11-Cefiderocol-Core-Submission-Dossier-V1.0.Pdf Core Submission Dossier PTJA11 Cefiderocol For the treatment of infections due to aerobic Gram-negative organisms in adults with limited treatment options Submitted by: Shionogi Contact details for administrative purposes Shionogi BV 33 Kingsway London WC2B 6UF Email address: [email protected] For agency completion Date of receipt: 14-04-2020 Version 3: Ameded dossier reflecting additional PK/PD analysis. Identifier: PTJA11 Disclaimer: The sole responsibility for the content of this document lies with the submitting manufacturer and neither the European Commission nor EUnetTHA are responsible for any use that may be made of the information contained therein. All rights reserved 1 Abbreviations A Aerobic AAT Appropriate antibacterial therapy ABC transporter ATP-binding cassette transporter ABSSSI Acute bacterial skin and skin structure infection Ac-BSI Acinetobacter spp. Bacteraemia AE Adverse event AET Appropriate empirical therapy ALAT Asociación Latinoamericana del Tórax AMK Amikacin AMR Antimicrobial resistance AN Anaerobic AR Antimicrobial-resistance AS Antimicrobial susceptibility AST Antimicrobial susceptibility tests AT Antibacterial therapy ATS American Thoracic Society AUC Area under the curve BAT Best available therapy BD Becton Dickinson BIA Budget impact analysis BIM Budget impact model BAL Bacterial β-lactamase BLI β-lactamase inhibitor BSI Bloodstream infection BSIMRS Bloodstream infection mortality risk score CAI Community-acquired infection CarbNS Carbapenem non-susceptible CASR Carbapenem- and ampicillin-sulbactam-resistant CAZ Ceftazidime/avibactam CDC Centres for Disease Control and Prevention CDI Clostridium difficile infection CFU Colony forming unit CHMP Committee for Medicinal Products for Human Use CI Confidence interval All rights reserved 2 cIAI Complicated intra-abdominal infection CLSI US Clinical & Laboratory Standards Institute CNSE Carbapenem-non-susceptible Enterobacteriaceae CPE Carbapenemase Producing Enterobacteriaceae CPFX Ciprofloxacin CR Carbapenem-resistant CRAB Carbapenem-resistant A. baumannii CRAc Carbapenem-resistant Acinetobacter spp. CRE Carbapenem-resistant Enterobacteriaceae CRGNB Carbapenem-resistant Gram-negative CRGNIs Carbapenem-resistant Gram-negative infections CRPA Carbapenem-resistant P. aeruginosa CSE Carbapenem-susceptible Enterobacteriaceae CSPA Carbapenem-susceptible P. aeruginosa CTX Cefotaxime cUTI Complicated urinary tract infection DALYs Disability-adjusted life-years DBO Diazabicyclooctane DGI German Society for Infectious Diseases Association DRG Disease-related groups EA Early assessment EAU European Association of Urology ECDC European Centre for Disease Prevention and Control EEA European Economic Area eHRB Emerging highly antibacterial resistant bacteria EMA European Medicines Agency EMEA Europe, Middle East, and Africa EOT End of treatment ERS European Respiratory Society ESBLs Extended-spectrum β-lactamases ESCMID European Society of Clinical Microbiology and Infectious Diseases ESICM European Society of Intensive Care Medicine EU European Union EUCAST European Committee on Antimicrobial Susceptibility Testing All rights reserved 3 FA Facultative anaerobic FDA U.S. Food and Drug Administration FUP Follow-up G3CREC Third-generation cephalosporin-resistant E. coli G3CSEC third-generation cephalosporin-susceptible E. coli GDP Gross domestic product Spanish Society of Infectious Diseases and Clinical GEIH-SEIMC Microbiology GNO Gram-negative organisms GVD Global Value Dossier HAI Hospital-acquired infection HAP Hospital acquired pneumonia HAS Haute Authorite de la Sante HCAI Healthcare-associated infection HCAP Healthcare-associated pneumonia Hr Hour HTA Health Technology Assessment HTAB Health Technology Assessment Body (c)IAI (complicated) Intra-abdominal infection IAT Inappropriate antibacterial therapy ICD International Classification of Disease ICU Intensive care unit ID-CAMHB Iron-depleted cation-adjusted Mueller Hinton broth IDSA Infectious Disease Society IET Inappropriate empiric therapy IMP IMP-type carbapenemases IPM/CS Imipenem/Cilastatin IQR Inter-quartile range IRAB Imipenem-resistant Acinetobacter baumannii ITT Intention-to-treat IV Intravenous KAPE Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter KPC Klebsiella pneumoniae carbapenemase LOS Length of stay All rights reserved 4 MA Marketing Authorization MAA Marketing Authorization Application MBLs Metallo-β-lactamases MCO Managed care organization MCR-1 Plasmid-mediated colistin-resistance MDR Multidrug resistant MDRA Multidrug resistant Acinetobacter MDRAB Multidrug resistant A. baumannii MDRP Multidrug resistant P. aeruginosa MDS Multidrug-sensitive ME Microbiologically evaluable (HD) MEPM (high dose) Meropenem MIC Minimum inhibitory concentration mITT Microbiological intention to treat MoA Mode of action NDA New drug application NDM New Delhi metallo-β-lactamase NHS National Health Service NI Nosocomial infections NICE National Institute of Health and Care Excellence NR Non-resistant NS Non- survivors OM Osteomyelitis OMT Outer membrane transporters OR Odds ratio OXA Oxacillinase PBC Positive blood culture PBPs Penicillin-binding proteins PCR Polymerase Chain Reaction PD Pharmacodynamic PDCO Paediatric Committee PDR Pan-drug-resistant PEG Percutaneous endoscopic gastroscopy PER Pseudomonas extended resistant β-lactamases PK Pharmacokinetic All rights reserved 5 PP Per Protocol PTA Probability of target attainment q8h Every 8 hours R Resistant RCT Randomized controlled trial RESP Respiratory tract RR Relative risk r-GNR Resistant gram-negative rod RTI Respiratory tract infection S Survivors SAE Serious adverse event SC Subcutaneous SCCM Society of Critical Care Medicine SD Standard deviation SEFH Spanish Society of Hospital Pharmacies Spanish Society of Preventive Medicine, Public Health and SEMPSPH Hygiene SICU Surgical intensive care unit SIS Surgical Infection Society SMC Siderophore monobactam conjugate sNDA Supplemental new drug application SOC Standard of care spp Species SSI Surgical site infection TOC Test of Cure tRNA Transfer ribonucleic acid UTI Urinary tract infection VAP Ventilator-acquired pneumonia VABP Ventilator-associated bacterial pneumonia VIM Verona integrin-encoded metallo-β-lactamase w/wo With or without WHO World Health Organization WSES World Society of Emergency Surgery XDR Extensively drug-resistance All rights reserved 6 Contents EXECUTIVE SUMMARY .......................................................................................... 14 1 Description and technical characteristics of the technology .......................... 23 1.1 Characteristics of the technology ................................................................... 25 1.1.1 Cefiderocol Structure .......................................................................... 26 1.1.2 Mechanism of action and cell entry .................................................... 27 1.1.3 Stability against β-lactamases ............................................................ 28 1.2 Regulatory status of the technology .............................................................. 29 2 Health problem and current clinical practice .................................................. 31 2.1 Overview of the disease or health condition .................................................. 32 2.1.1 Overview of Gram-negative bacteria .................................................. 33 2.1.2 Antimicrobial resistance ...................................................................... 35 2.1.3 Overview of infection sites .................................................................. 39 2.1.4 Risk and prognostic factors for MDR and CR infections ..................... 41 2.1.5 Epidemiology ...................................................................................... 42 2.1.6 Mortality .............................................................................................. 47 2.1.7 Quality of Life ...................................................................................... 48 2.1.8 Disability Adjusted Life Years (DALYs) ............................................... 48 2.1.9 Delayed effective therapy ................................................................... 49 2.2 Target population ........................................................................................... 52 2.3 Clinical management of the disease or health condition ................................ 57 2.3.1 Key information on currently available treatments in Europe .............. 59 2.3.2 Site-specific vs. pathogen-specific guidelines..................................... 63 2.3.3 Specific recommendations.................................................................. 63 2.3.4 Specific considerations of CR infections ............................................. 63 2.4 Comparators in the assessment .................................................................... 87 2.4.1 General considerations ....................................................................... 87 2.4.2 Selection of relevant comparators for the assessment ....................... 89 3 Current use of the technology........................................................................ 94 3.1 Current use of the technology........................................................................ 95 3.2 Reimbursement and assessment status of the technology ........................... 96 4 Investments and tools required...................................................................... 97 4.1
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