The Antibiotic Pipeline: How “New” is New

In a recent ‘Viewpoint’ article, Dr. Fauci, Director of NIAID, mentioned that “industry has expanded the pipeline of new antibacterial drugs…with 14-agents currently in phase 3 clinical trials”.[1]

Regarding the number of drugs in late development, his statement may be correct but many of these drugs are anything but new.  Reviewing information from various public sources, [2] [3], there are no antibacterials with a novel mode of action (MoA) in Phase 3 development.

In development are:  new combination B-lactam/B-lactamase inhibitors, modified quinolones, glycopeptides, tetracyclines and oxazolidinones.   Based on recent tallies of the antibacterial pipeline, subtracting drugs for topical use, for inhalation or for C. difficile infection, here the status:

PHASE 3        Status: 6/15/2014
PLEASE BE PATIENT – THIS WILL BE UPDATED SHORTLY
 [table “6” not found /]

All in all, there are 10 drugs from well-known drug classes.  With ceftobiprole’s fate somewhat uncertain in the US, and oritavancin and tedizolid expected to gain approval shortly, we are left with seven (7) late-stage candidates.  They promise to bring small incremental benefits, but benefits nonetheless.  History has shown that progress in this area often comes in small steps.  Certainly, the extended activity B-lactam + BL-inhibitors will prove useful in places where ESBL and MDR pathogens have become resistant to penems antibiotics.

The Phase 2 pipeline is quite a bit more interesting.  In addition to existing drug classes, there are also pleuromutilins, defensins, Fabl- and PDF inhibitors.

PHASE 2        Status: 6/15/2014
PLEASE BE PATIENT – THIS WILL BE UPDATED SHORTLY
 [table “5” not found /]

The pleuromutilin class of drugs are already widely used in veterinary medicine and considered safe for animals.  Nonetheless, more data confirming safety in humans is needed.

PDF inhibitors have a checkered history as resistance develops rather fast.  There are also concerns about toxicities.  Likewise, quinolones had problems with rapid development of MRSA resistance in the clinic. Presumably, the preclinical data packages are addressing these issues and support development of both drug classes.

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References

[1] A. Fauci.  JAMA 2014; 311: 1853
[2] http://www.pewhealth.org/other-resource/antibiotics-currently-in-clinical-development-85899541594
[3] M. Pucci  Microbe 2014; 9: 147

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