EUnetHTA Joint Action 3 WP4 Relative effectiveness assessment of pharmaceutical technologies CEFIDEROCOL (FETCROJA®) FOR THE TREATMENT OF INFECTIONS DUE TO AEROBIC GRAM-NEGATIVE ORGANISMS IN ADULTS WITH LIMITED TREATMENT OPTIONS Project ID: PTJA11 Version 1.0, 16/06/2020 Template version 2.1, April 2020 This Joint Assessment is part of the project / joint action ‘724130 / EUnetHTA JA3’ which has received funding from the European Union’s Health Programme (2014-2020) Dec2015 ©EUnetHTA, 2015. Reproduction is authorised provided EUnetHTA is explicitly acknowledged 1 Cefiderocol for the treatment of infections due to aerobic Gram-negative bacteria in adult patients DOCUMENT HISTORY AND CONTRIBUTORS Version Date Description V0.1 01/05/2020 First draft V0.2 01/06/2020 Input from dedicated reviewers has been processed V0.3 05/06/2020 Input from medical editor and manufacturer(s) has been processed V1.0 16/06/2020 Final assessment report Disclaimer The content of this Assessment Report represents a consolidated view based on the consensus within the Authoring Team; it cannot be considered to reflect the views of the European Network for Health Technology Assessment (EUnetHTA), EUnetHTA’s participating institutions, the European Commission and/or the Consumers, Health, Agriculture and Food Executive Agency or any other body of the European Union. The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains. Assessment team Author(s) Norwegian Medicines Agency, NOMA, Norway Co-Author(s) Zorginstituut Nederland, ZIN, The Netherlands Dedicated Agencia Española de Medicamentos y Productos Sanitarios, AEMPS, Spain Reviewer(s) French National Authority for Health, HAS, France Other Institute for Quality and Efficiency in Health Care, IQWiG, Germany - IQWiG provided high contributor(s) level comments on an early version of the assessment report Due to the impact of the COVID-19 measures, a change in the Authoring Team and in the timelines was necessary. The EUnetHTA response to COVID-19 can be found here. As presented in the PTJA11 Project Plan, the AIFA team (Italy) had to withdraw from its authoring role in the Joint Assessment of cefiderocol due to the COVID-19 outbreak and its involvement in the management of this emergency. EUnetHTA would like to acknowledge the contribution of the Italian team in the entire scoping phase, including the elaboration of the PICO, and finalisation of the project plan. ZIN (the Netherlands) stepped up as co-author, but they were not involved in the scoping phase of the project. Further contributors External experts Simone Lanini MD, MSc Answered specific questions during the scoping phase of the Specialist in Infectious Disease assessment. Epidemiology and Preclinical Research Department INMI Lazzaro Spallanzani IRCCS Rome Italy Dr. Annie Navarro Rolon Hospital Universitario Mútua de Terrassa Manufacturer(s) [v0.2] Shionogi Completion of the Submission Dossier Factual accuracy check Medical editor [v0.2] Nextgenediting Medical editing of the report Patient(s) / patient organisation(s) / citizens NA No patient or consumer organisation replied to the open call for patient input Project Management Zorginstituut Nederland (ZIN), Coordination between involved parties throughout the assessment Netherlands June 2020 EUnetHTA Joint Action 3 WP4 2 Cefiderocol for the treatment of infections due to aerobic Gram-negative bacteria in adult patients Copyright EUnetHTA assessments are published under a “CC/BY/NC” Creative Commons Licence. How to cite this assessment Please cite this assessment as follows: EUnetHTA PTJA11. Authoring Team. CEFIDEROCOL (FETCROJA®) FOR THE TREATMENT OF INFECTIONS DUE TO AEROBIC GRAM-NEGATIVE ORGANISMS IN ADULTS WITH LIMITED TREATMENT OPTIONS. Joint Assessment. Diemen (The Netherlands): EUnetHTA; 2020. [date of citation]. 122 pages. Report No.: PTJA11. Available from: https://www.eunethta.eu. Enquiries about this assessment should be made to the EUnetHTA Secretariat ([email protected]). June 2020 EUnetHTA Joint Action 3 WP4 3 Cefiderocol for the treatment of infections due to aerobic Gram-negative bacteria in adult patients TABLE OF CONTENTS EXECUTIVE SUMMARY OF THE ASSESSMENT OF CEFIDEROCOL ........................................ 9 INTRODUCTION .............................................................................................................................. 9 OBJECTIVE AND SCOPE .................................................................................................................. 9 METHODS ................................................................................................................................... 10 RESULTS .................................................................................................................................... 10 DISCUSSION ................................................................................................................................ 13 CONCLUSION .............................................................................................................................. 14 1 BACKGROUND ........................................................................................................................ 15 1.1 OVERVIEW OF THE DISEASE OR HEALTH CONDITION ................................................................. 15 1.2 CURRENT CLINICAL PRACTICE ................................................................................................ 15 1.3 FEATURES OF THE INTERVENTION .......................................................................................... 16 2 OBJECTIVE AND SCOPE ....................................................................................................... 17 3 METHODS ................................................................................................................................ 20 3.1 INFORMATION RETRIEVAL ....................................................................................................... 20 3.2 DATA EXTRACTION ................................................................................................................ 21 3.3 RISK OF BIAS ASSESSMENT .................................................................................................... 21 3.4 RESULTS AND ANALYSES OF INCLUDED STUDIES ..................................................................... 22 3.5 PATIENT INVOLVEMENT .......................................................................................................... 23 4 RESULTS ................................................................................................................................. 24 4.1 INFORMATION RETRIEVAL ....................................................................................................... 24 4.2 STUDIES INCLUDED IN THE ASSESSMENT................................................................................. 24 4.3 EXCLUDED STUDIES .............................................................................................................. 27 4.4 CHARACTERISTICS OF THE INCLUDED STUDIES ........................................................................ 28 4.5 OUTCOMES OF INCLUDED STUDIES ......................................................................................... 34 4.6 RISK OF BIAS OF INCLUDED STUDIES ....................................................................................... 34 4.7 EXTERNAL VALIDITY OF INCLUDED STUDIES ............................................................................. 35 4.8 RESULTS ON CLINICAL EFFECTIVENESS AND SAFETY ................................................................ 36 5 PATIENT INVOLVEMENT ........................................................................................................ 63 6 DISCUSSION ............................................................................................................................ 64 6.1 ASSESSMENT OF PICO POPULATION 1 ................................................................................... 64 6.2 ASSESSMENT OF PICO POPULATION 2 ................................................................................... 65 6.3 OTHER SHORTCOMINGS IN THE DOCUMENTATION .................................................................... 66 6.4 SUPPORTIVE EVIDENCE (IN VITRO, PK/PD, CLINICAL PHARMACOLOGY, NMA) .......................... 66 7 CONCLUSION .......................................................................................................................... 68 8 REFERENCES ......................................................................................................................... 69 APPENDIX 1: GUIDELINES FOR DIAGNOSIS AND MANAGEMENT ........................................ 74 APPENDIX 2: FEATURES OF THE TECHNOLOGIES ................................................................. 87 APPENDIX 3: OUTCOMES DEFINITIONS .................................................................................... 96 APPENDIX 4: NMA ...................................................................................................................... 102 APPENDIX 5: OTHER EVIDENCE .............................................................................................. 113 CHARACTERISTICS OF IN VITRO SURVEILLANCE STUDIES ............................................................. 113 RESULTS OF IN VITRO SURVEILLANCE STUDIES ............................................................................ 113 CHARACTERISTICS