Table 7 Compounds discontinued or likely to have been discontinued from clinical development since 2018 or the previous review [23]
From: Antibiotics in the clinical pipeline as of December 2022
Name (synonym) [References] | Compound class (lead source); mode of action | Last known status and indication |
|---|---|---|
iclaprim [374] | trimethoprim (S); dihydrofolate reductase (DHFR) | NDA, IV/po; ABSSSI (Motif Bio) – FDA required an additional phase-III trial and development was halted |
“ethambutol analog” (S); mycolic acid transporter inhibitor (cell wall) | po; TB (Sequella) – a Russian phase II/III trial was completed in 2017 by Infectex [362, 363]; funding for further development is being sought by Sequella (Rockville, MD, USA) | |
bis-benzimidazole (S) [potential new class]; cell division inhibitor | Phase-III; po topical; CDI (Summit) – ridinilazole was non-superior compared to vancomycin in terms of clinical response, and an additional phase-III trial would have been required [374] | |
monobactam (NP); PBP (cell wall) | IV; cUTI and cIAI (Boston Pharmaceuticals) – licensed by Novartis to Boston Pharmaceuticals (Cambridge, MA, USA) in July 2018, but there has been no further development | |
fluoroquinolone (S); DNA gyrase | po topical; CDI (Otsuka) – discontinued in 2020 for CDI and Crohn’s Disease | |
tetracycline (NP); protein synthesis inhibition | IV; G-ve (Tetraphase) – phase-I trial (NCT03691584) was completed in December 2019 and there has been no further development; Tetraphase was acquired by La Jolla Pharmaceutical in July 2020, who are now part of Innoviva (Burlingame, CA, USA) | |
tetracycline (NP); protein synthesis inhibition | IV/po; G+ve/ G-ve (Tetraphase) – phase-I trials (e.g., NCT03024034) completed in 2018 and there has been no further development; Tetraphase was acquired by La Jolla Pharmaceutical in July 2020, who are now part of Innoviva (Burlingame, CA, USA) | |
polymyxin (NP); membrane permeabilizer (cell wall) | IV; G-ve (Spero) – phase-I trials (NCT03022175 and NCT03376529) completed in 2017 and development was discontinued in 2020 | |
cephalosporin siderophore (NP); PBP (cell wall) | IV (Geom) – phase I trial (ACTRN12618001980224) started in March 2019 but was halted due to safety concerns | |
BCM-0184 | not disclosed | po (& topical); G+ve (Biocidium) – phase-I trial was not registered and there has been no update |
niclosamide (ATx201) [396] | salicylanilide (S); oxidative phosphorylation; quorum sensing | topical; H. pylori; impetigo (Union Therapeutics) – phase-II trials (NCT03009734 and NCT03429595) finished in 2018; only listed in their pipeline for COVID-19 prophylaxis (NCT04932915) |
auranofin [236] | auranofin (S); thiol-redox homeostasis | po; TB (The Aurum Institute) – phase-II trial (NCT02968927) has not been updated since January 2019 |
mAb rifamycin conjugate (ADC); RNA synthesis | IV; G+ve (Genentech) – phase-I trial (NCT03162250) completed in January 2020 but DSTA4637S is not listed on their pipeline |
