Novel medicines in the R&D pipeline that offer a much lower risk of resistance
Amplyx, Debiopharm, Entasis, GSK, Nabriva, Otsuka, Scynexis and Summit
Eight companies have clinical-stage medicines that qualify as ‘novel’ - meaning they are more likely to remain effective for longer against resistant pathogens.
As antimicrobial resistance increases, we increasingly need new antibacterials and antifungals that work in novel ways to remain effective against bacteria and fungi for as long as possible. Novel compounds offer the best chance for new antibacterials and antifungals to remain effective for longer because the compound is different enough from existing agents to minimise the risk of cross-resistance.
How does the Benchmark define 'novelty'?
The Benchmark uses four criteria defined by the World Health Organization to determine whether an antibacterial or antifungal medicine in the pipeline is novel. These criteria are:
1. New chemical class;
2. New target;
3. New mode of action;
4. Absence of cross-resistance.
Eight companies in scope of the Benchmark have projects in the clinical stages of development that are considered novel according to the WHO criteria. Collectively, the eight companies are developing nine novel projects: seven target bacterial agents; and two target fungi.
Five companies have clinical medicines that qualify as novel
Five projects meet all criteria for novelty
Five companies have projects that meet all criteria for novelty: Amplyx, Debiopharm, GSK, Otsuka and Summit. For example, Summit is developing ridinilazole, a bisbenzimidazole to treat infection from Clostridioides difficile – one of the most common causes of hospital-acquired infections. The worldwide increased incidence of Clostridioides difficile has been attributed to an increase in resistance to fluoroquinolones. Amplyx has fosmanogepix, an antifungal with broad in vitro activity against fungal pathogens, including Candida spp., as well as Aspergillus, Cryptococcus, coccidioidomycosis, and rare mould infections caused by Scedosporium spp., Fusarium spp., and Mucorales fungi.
What other novel medicines are showing promise?
The remaining novel projects by Entasis, GSK, Nabriva and Scynexis, meet at least one criterion. Both Entasis' zoliflodacin and GSK's gepotidacin aim to treat Neisseria gonorrhoeae. This pathogen has the potential to rapidly develop resistance, and experts have warned that it could become resistant to all currently available antibiotics in the future. As novel medicines, both zoliflodacin and gepotidacin have important differences from existing medicines, which may help to preserve its effectiveness.
Further, Nabriva’s lefamulin (Xenleta™) is the first antibiotic in the pleuromutilin class to be indicated for the treatment of community-acquired bacterial pneumonia (CABP). Approved by the FDA in August 2019, this is the first antibiotic with a novel mechanism of action in nearly 20 years; its mechanism results in a low propensity for the development of resistance, and lack of cross-resistance. Nabriva has designed lefamulin (Xenleta™) to be administered in two formulations (oral and intravenous). For adults with CABP, it is an important new single-drug treatment option.