Antibiotic Development Pipeline Running Thin, WHO Warns

As more deadly pathogens develop resistance to antibiotics, a new World Health Organization (WHO) report warns that the current clinical pipeline of antibiotics in development is insufficient to combat the threat.

The report focuses on the development pipeline for potential new antibiotics to fight against critical and high-priority pathogens which are increasingly becoming resistant, including Mycobacterium tuberculosis, which causes tuberculosis (TB), and Clostridium difficile, which leads to C. diff infection.

“Antimicrobial resistance is a global health emergency that will seriously jeopardize progress in modern medicine,” said Tedros Adhanom Ghebreyesus, PhD, director-general of WHO, in a press release announcing the report. “There is an urgent need for more investment in research and development for antibiotic-resistant infections including TB, otherwise we will be forced back to a time when people feared common infections and risked their lives from minor surgery.”

According to the report, there are 51 new antibiotics in development, including combinations, and 11 biologic products meant to complement, not replace, antibiotics. There are 7 new agents for TB in clinical trials, and 9 in development for C. difficile.

However, there are relatively few innovative agents that represent a new chemical class, are not cross-resistant to existing antibiotics, or have a novel target or mechanism of action. Just 5 of the 32 new chemical antibiotics developed for use against priority pathogens represent a new chemical class, and only 8 priority agents meet at least 1 of the 4 requirements to be considered innovative.

The report authors concluded that the current pipeline is “insufficient” against WHO-designated priority pathogens and TB. They attributed some of this lagging development to the scientific difficulty of developing new chemical classes with novel binding sites. However, they also implied that some pathogens that mainly affect the poor do not represent a profitable target for drug developers.

For instance, there are no agents in development against resistant Salmonella typhi, which commonly causes typhoid fever in developing countries. TB also mainly affects low-income populations, so “there is very little commercial incentive to invest in developing new treatments,” the report stated.

Economic incentives play a role in determining the type of drugs developed, not just the pathogens they are developed to target. The report noted the scarcity of oral drugs in the pipeline, which “are required in countries with high resistance rates in community-treated infections such as urinary tract infections,” particularly in low- and middle-income countries.

“More investment is needed in basic science, drug discovery and clinical development,” the report concluded, particularly for drugs to combat the critical priority resistant pathogens.

Development may be encouraged through regulatory support and partnerships between pharmaceutical companies and research institutions. However, a more robust antibiotic development pipeline must be accompanied by efforts to promote responsible stewardship of existing antibiotics, which will be detailed in a set of guidelines forthcoming from the WHO.