TABLE 3.
Traditional antibacterial agents and combinations in NDA and phase 3 clinical development against WHO priority pathogens
| Name (synonym) | Phase | Antibacterial class | Route of administration | Developer | Expected activity against priority pathogensa |
Innovationb |
||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CRAB | CRPA | CRE | OPP | NCR | CC | T | MoA | |||||
| Solithromycin (T-4288) | NDAc | Macrolide | i.v. & oral | iFUJIFILM Toyama Chemical | NA | NA | NA | ●d | — | — | — | — |
| Sulopenem, Sulopenem etzadroxil/probenecid | NDAe | β-Lactam (penem) | i.v. & oral | Iterum | ○ | ○ | ○f | NA | — | — | — | — |
| Durlobactam (ETX-2514) + sulbactam | 3 | DBO-BLI/PBP2 binder + β-lactam-BLI/PBP1,3 binder | i.v. | Entasis | ● | ○ | ○ | NA | — | — | — | — |
| Taniborbactam (VNRX-5133) + cefepime | 3 | Boronate BLI + β-lactam (cephalosporin) | i.v. | VenatoRx/GARDP | ○ | ● | ● | NA | ? | ✓ | — | — |
| Enmetazobactam (AAI-101) + cefepime | 3 | BLI + β-lactam (cephalosporin) | i.v. | Allecra | ○ | ○ | ○g | NA | — | — | — | — |
| Zoliflodacin | 3 | Spiropyrimidenetrione (topoisomerase inhibitor) | Oral | Entasis/GARDP | NA | NA | NA | ●d | ✓ | ✓ | — | ✓ |
| Gepotidacin | 3 | Triazaacenaphthylene (topoisomerase inhibitor) | i.v. & oral | GSK | NA | NA | NA | ●d | ? | ✓/?h | — | ✓ |
| Nafithromycin (WCK-4873) | 3 | Macrolide | Oral | Wockhardt | NA | NA | NA | ●d | — | — | — | — |
| Benapenem | 2/3 | β-Lactam (carbapenem) | i.v. | Sichuan Pharmaceutical | ○ | ○ | ○ | NA | — | — | — | — |
Pathogen activity: ●, active; ?, possibly active; ○, not or insufficiently active; NA, activity not assessed, as the antibiotic is focused and developed for only either Gram-positive cocci or Gram-negative rods. Agents not active against critical-priority pathogens were assessed for activity against OPP, which includes the high and medium WHO priority pathogens.
Innovation assessment: ✓, criterion fulfilled; ?, inconclusive data; —, criterion not fulfilled. CC, chemical class; MOA, new mode of action; NCR, no cross-resistance; T, new target.
Solithromycin NDA for otorhinolaryngological infections submitted in Japan in April 2019.
OPP target pathogens: solithromycin, S. pneumoniae; nafithromycin, S. aureus and S. pneumoniae; gepotidacin, N. gonorrhoeae and E. coli; zoliflodacin, N. gonorrhoeae.
Sulopenem etzadroxil NDA submitted in USA for uncomplicated UTI (uUTI) in November 2020.
Active against ESBL-producing cephalosporin-resistant but not carbapenem-resistant Enterobacterales.
Active against ESBL-producing cephalosporin-resistant and some KPC-producing CRE.
Gepotidacin is being tested in two distinct phase 3 programs: gonorrhea (NCR ✓) and uUTI (NCR ?).