TABLE 3.
Antimicrobial drugs in the clinical pipeline as of February 2020a
| Drug name | Drug class | Drug target | Development stage | Company | Pathogen target | Applicationb | Information of noteb |
|---|---|---|---|---|---|---|---|
| Plazomicin (Zemdri) | Aminoglycoside | 30S subunit of bacterial ribosome | U.S. FDA approved on 26 June 2018 | Achaogen Inc. | E. coli, K. pneumoniae, Proteus mirabilis, E. cloacae, and CRE | cUTI including acute pyelonephritis | Nephrotoxicity has been reported |
| Cefiderocol (Fetroja) | Siderophore–β-lactam (cephalosporin) | PBP | U.S. FDA approved on 14 November 2019 | Shionogi & Co. Ltd. | CRE, CRAB, and CRPA | cUTI | |
| Imipenem + cilastatin + relebactam (Recarbrio) | β-Lactam (carbapenem) + β-lactamase inhibitor (diazabicyclooctane) | PBP, β-lactamase | U.S. FDA approved on 17 July 2019; E.U. EMA approved on 13 February 2020 | Merck & Co., Inc. | CRE and CRPA | cUTI including pyelonephritis, cIAI, and HA and VA bacterial pneumonia | |
| Meropenem- vaborbactam (Vabomere/Vaborem) | β-Lactam (carbapenem) + β-lactamase inhibitor (cyclic boronate) | PBP, β-lactamase | U.S. FDA approved on 30 August 2017; E.U. EMA approved on 20 November 2018 | Rempex Pharmaceuticals Inc. (wholly owned subsidiary of The Medicines Co.) | E. coli, K. pneumoniae, E. cloacae species complex, and CRE | cUTI including pyelonephritis | Anaphylactic and central nervous system reactions have been reported |
| Cefepime + zidebactam (WCK 5222) | β-Lactam (cephalosporin) + β-lactamase inhibitor (diazabicyclooctane) | PBP, β-lactamase | Phase I | Wockhardt Ltd. | ESKAPE pathogens, pneumococci, and streptococci | cUTI and HA and VA bacterial pneumonia | Highly broad-spectrum antimicrobial |
| ETX0282 + cefpodoxime + proxetil (ETX0282CPDP) | β-Lactam (cephalosporin) + β-lactamase inhibitor (diazabicyclooctane) | PBP, β-lactamase | Phase I | Entasis Therapeutics Inc. | MDR A. baumannii and CRAB | UTI | Designated a QIDP by U.S. FDA and awarded fast-track review |
| Meropenem + nacubactam OP0595/RG6080) | β-Lactam (carbapenem) + β-lactamase inhibitor (diazabicyclooctane) | PBP, β-lactamase, PBP2 | Phase I | Meiji Seika Pharma Co. Ltd./Fedora Pharmaceuticals Inc. (Roche licensee) | CRE, CRPA | Bacterial infections | |
| Cefepime + AAI101 | β-Lactam (cephalosporin) + β-lactamase inhibitor (β-lactam) | PBP, β-lactamase | Phase III | Allecra | CRE | cUTI including pyelonephritis, cIAI, and HA and VA bacterial pneumonia | Designated a QIDP by U.S. FDA and awarded fast-track review |
| Cefepime + taniborbactam (VNRX-5133) | β-Lactam (cephalosporin) + β-lactamase inhibitor (cyclic boronate) | PBP, β-lactamase | Phase III | VenatoRx Pharmaceuticals Inc. | MDR enteric organisms and ESBL-, KPC-, OXA-, and NDM-, VIM-producing P. aeruginosa | cIAI and cUTI | Designated a QIDP by U.S. FDA and awarded fast-track review |
| Sulbactam-durlobactam (ETX2514SUL) | β-Lactam (sulbactam) + β-lactamase inhibitor (diazabicyclooctane) | PBP, β-lactamase | Phase III | Entasis Therapeutics Inc. | CRAB | A. baumannii infections | |
| BOS-228 (LYS228) | β-Lactam (monobactam) | PBP | Phase II | Boston Pharmaceuticals (licensed from Novartis AG) | CRE | cUTI and cIAI | May be used in combination with other β-lactam antibiotics |
| Ceftobiprole (Zeftera) | β-Lactam (cephalosporin) | PBP | Phase III; E.U. EMA approved via decentralized procedure; Australian TGA approved for HA and CA pneumonia on 8 February 2016; Health Canada approved for HA and CA pneumonia on 12 October 2015; Health Canada approved for ABSSSI in June 2008 | Basilea Pharmaceutica | S. aureus | ABSSSI and CA and HA bacterial pneumonia | |
| Tebipenem-pivoxil (SPR994/SPR859) | β-Lactam (carbapenem) | PBP | Phase III; Japanese PMDA approved on 22 April 2009 | Spero Therapeutics Inc. | ESBL-producing E. coli and K. pneumoniae | CA bacterial pneumonia and complicated UTI | Oral administration for home-based care |
| Sulopenem/sulopenem-etzadroxil | β-Lactam (carbapenem) | PBP | Phase III | Iterum Therapeutics Ltd. | MDR Gram-negative pathogens | cUTI, uncomplicated UTI, and cIAI | Available as oral and intravenous preparations |
| Cefilavancin (TD-1792) | Glycopeptide–β-lactam (cephalosporin) hybrid | PG chain elongation, PBP | Phase III | R-Pharm/Theravance Biopharma Inc. | ABSSSI | ||
| Delafloxacin (Baxdela/Quofenix) | Fluoroquinolone | Bacterial type II topoisomerase | U.S. FDA approved on 19 June 2017; E.U. EMA approved on 16 December 2019 | Melinta Therapeutics Inc. | ESKAPE pathogens except A. baumannii | ABSSSI | Serious adverse reactions, including tendinitis, tendon rupture, and neuropathy |
| Lascufloxacin (Lasvic) | Fluoroquinolone | Bacterial type II topoisomerase | Japanese PMDA approved on 20 September 2019 | Kyorin Pharmaceutical Co. Ltd. | Klebsiella spp, Enterobacter spp., MRSA, and S. pneumoniae | CA bacterial pneumonia | Activity against MRSA comparable to that of linezolid and vancomycin |
| Alalevonadifloxacin + levonadifloxacin (WCK 771/WCK 2349) | Fluoroquinolone | Bacterial type II topoisomerase | Phase III | Wockhardt Ltd. | MRSA, VRSA, and MDR pneumococci, E. coli, and K. pneumoniae | ABSSSI and HA bacterial pneumonia | Active against MSRA biofilm |
| OPS-2071 | Quinolone | Bacterial type II topoisomerase | Phase II | Otsuka Pharmaceutical Co. Ltd. | C. difficile | C. difficile infection | |
| Nemonoxacin (Tiagexyn) | Quinolone | Bacterial type II topoisomerase | Phase II; approved in Taiwan, Russia, Turkey, China, and Latin America during 2016 | TaiGen Biotechnology Co. Ltd. | S. aureus | CA bacterial pneumonia, diabetic foot infection, and ABSSSI | Designated a QIDP by U.S. FDA and awarded fast-track review |
| Zoliflodacin (ETX0914) | Spiropyrimidinetrione | Bacterial type II topoisomerase | Phase III | Entasis Therapeutics Inc. | N. gonorrhoeae | Uncomplicated N. gonorrhoeae infection | Designated a QIDP by U.S. FDA and awarded fast-track review |
| ACX-362E | DNA polymerase IIIC inhibitor | DNA polymerase IIIC | Phase 1 | Acurx Pharmaceuticals LLC | C. difficile | C. difficile infections | Potential to be applied against all ESKAPE pathogens |
| MGB-BP-3 | Distamycin | DNA minor groove binder | Phase II | MGB Biopharma Ltd. | C. difficile | C. difficile-associated diarrhea | Targets C. difficile in vegetative state before it sporulates |
| Sodium fusidate (ARV-1801) | Fusidane | Elongation factor G | Phase III; approved (for dosing regimens as an alternative to what is currently being tested in clinical trials) for ABSSSI in South Korea, Japan, Canada, the European Union, Australia, New Zealand, Thailand, India, and Taiwan | Arrevus Ltd. | MRSA | ABSSSI and prosthetic joint infections | Granted orphan drug designation by U.S. FDA |
| Omadacycline (Nuzyra) | Tetracycline | 30S subunit of bacterial ribosome | U.S. FDA approved on 2 October 2018; E.U. EMA considered granting marketing authorization | Paratek Pharmaceuticals Inc. | ESKAPE pathogens | CA bacterial pneumonia and ABSSSI | Favorable oral and/or intravenous administration; Paratek Pharmaceuticals withdrew from E.U. EMA marketing authorization approval on 9 October 2019 due to commercial feasibility issues |
| Eravacycline (Xerava) | Tetracycline | 30S subunit of bacterial ribosome | U.S. FDA approved on 27 August 2018; E.U. EMA approved on 9 September 2018 | Tetraphase Pharmaceuticals Inc. | ESKAPE pathogens, including CRE and CRAB | cIAI | Not indicated for treatment of complicated UTI |
| KBP-7072 | Tetracycline | 30S subunit of bacterial ribosome | Phase I | KBP BioSciences Pharmaceutical Technical Co. Ltd. | CA bacterial pneumonia | Designated a QIDP by U.S. FDA and awarded fast-track review | |
| TP-271 | Tetracycline | 30S subunit of bacterial ribosome | Phase I | Tetraphase Pharmaceuticals Inc. | Respiratory pathogens | CA bacterial pneumonia | Designated a QIDP by U.S. FDA and awarded fast-track review |
| TP-6076 | Tetracycline | 30S subunit of bacterial ribosome | Phase I | Tetraphase Pharmaceuticals Inc. | CRE and CRAB | Bacterial infections | CARB-X funded ($4 million) |
| Lefamulin (Xelenta) | Pleuromutilin | 50S subunit of bacterial ribosome | U.S. FDA approved on 19 August 2019; E.U. EMA marketing authorization application submitted in May 2019 (now accepted); Chinese NMPA granted clinical trial application approval on 13 June 2019 | Nabriva Therapeutics AG | MRSA | ABSSSI and CA and HA bacterial pneumonia | Low toxicity profile; available as both intravenous and oral treatments |
| Delpazolid (LCB01-0371) | Oxazolidinone | 50S subunit of bacterial ribosome | Phase II | LegoChem Biosciences Inc. | Bacterial infections and tuberculosis | Granted orphan drug designation, a QIDP, and fast-track review by U.S. FDA | |
| DNV3837 (MCB3837) | Oxazolidinone-quinolone hybrid | 50S subunit of bacterial ribosome, bacterial type II topoisomerase | Phase I | Deinove SA (formerly Morphochem AG) | C. difficile | C. difficile infections | Narrow spectrum for C. difficile, which may reduce gut dysbiosis; designated a QIDP by U.S. FDA and awarded fast-track review |
| Contezolid (MRX-I/MRX-415) | Oxazolidinone | 50S subunit of bacterial ribosome | Phase III | MicuRx Pharmaceuticals Inc. | MRSA and S. pneumoniae | ABSSSI | |
| Nafithromycin (WCK 4873) | Macrolide | 50S subunit of bacterial ribosome | Phase II | Wockhardt Ltd. | MDR pneumococci | CA bacterial pneumonia | High level of lung and alveolar macrophage penetration; low hepatic toxicity |
| SPR206 | Polymyxin | Cell membrane | Phase I | Spero Therapeutics Inc. | CRE, CRPA, CRAB, and XDR strains | cUTI and HA and VA bacterial pneumonia | Reduced nephrotoxicity |
| SPR741 | Polymyxin | Cell membrane | Phase I | Spero Therapeutics Inc. | Gram-negative ESKAPE pathogens | Bacterial infections | Potentiator with reduced nephrotoxicity; antibiotic paring is yet to be announced |
| Afabicin (Debio 1450) | Benzofuran naphthyridine | FabI | Phase II | Debiopharm International SA | Staphylococcus sp. | ABSSI | Low propensity for resistance development |
| CG-549 | Benzyl pyridinone | FabI | Phase II | Crystal Genomics Inc. | MRSA and VRSA | ABSSSI | |
| Iclaprim | 2,4-Diaminopyrimidine | Dihydrofolate reductase | Complete response letter to Investigational New Drug application (U.S. FDA) | Motif Bio PLC | Gram-positive bacteria, including MRSA | ABSSSI and HA and VA bacterial pneumonia | Granted orphan status and designated a QIDP by U.S. FDA; low propensity for resistance development |
| CRS3123 | Diaryldiamine | Methionyl-tRNA synthetase | Phase I | Crestone Inc. | C. difficile | C. difficile infections | Narrow spectrum for C. difficile, which may reduce gut dysbiosis |
| Brilacidin | Defensin mimetic | Cell membrane | Phase II | Innovation Pharmaceuticals Inc. | ABSSSI | New class of antibiotic; designated a QIDP by U.S. FDA and awarded fast-track review | |
| Murepavadin (POL7080) | Antimicrobial peptide mimetic | LptD | Phase III | Polyphor Ltd. | CRPA | HA and VA bacterial pneumonia (caused by P. aeruginosa) | Designated a QIDP by U.S. FDA and awarded fast-track review |
| Ridinilazole (SMT 19969) | Bis-benzimidazole | Inhibition of cell division and reduction of toxin production | Phase III | Summit Therapeutics PLC | C. difficile | C. difficile infection | Narrow spectrum for C. difficile, which may reduce gut dysbiosis; designated a QIDP by U.S. FDA and awarded fast-track review |
a
The table includes data from reference 390. Abbreviations: CA, community acquired; HA, hospital acquired; VA, ventilator associated; UTI, urinary tract infection; cUTI, complicated UTI; cIAI, complicated intra-abdominal infection; ABSSSI, acute bacterial skin and skin structure infection; QIDP, qualified infectious disease product; U.S. FDA, U.S. Food and Drug Administration; E.U. EMA, European Union European Medicines Agency; Australian TGA, Australian Therapeutic Goods Administration; Chinese NMPA, Chinese National Medical Products Administration; Japanese PMDA, Japanese Pharmaceutical and Medical Devices Agency; BARDA, U.S. Biomedical Advanced Research and Development Authority; PBP, penicillin-binding protein; PG, peptidoglycan; MRSA, methicillin-resistant S. aureus; CRE, carbapenem-resistant Enterobacterales; CRAB, carbapenem-resistant A. baumannii; CRPA, carbapenem-resistant P. aeruginosa; XDR, extremely drug resistant.
b
As defined by the company website.