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By: Vishnu dutt sharma

Rapid emervishnu-sharma-headshotgence of antimicrobial resistance poses a serious concern to the efficacy of classical antimicrobial therapies. The resistant bugs have infected up to 2 million Americans and killed at least 23,000 each year. Adding insult to an injury, stringent regulatory requirements are making the new drug development process extensive as well as expensive. On an average, pharma companies invest $5 billion in research and development for each drug. Therefore, the pharma industries are losing interest in developing new antibiotics. For instance, Pfizer was a leader of antibiotic development for manufacturing penicillin, but it had to close their antibiotic research facility in Connecticut for financial reasons. The World Health Organization has described the situation as “a race against time.” Lawmakers are trying to allure pharmaceutical companies with incentives to address a major drought in antibiotic discovery. One major step was the enactment of Generating Antibiotic Incentives Now (GAIN) Act in 2012, which extends drug-patent exclusivity for an additional five years and expedites the drug approval process. Thanks to the GAIN act, 50 new anti-infective therapies have already been approved since 2012.

There is an urgent need to develop new antibiotics that exploit newer pathways to avoid early drug resistance, and to pursue smart approaches such as dose combinations to conserve the efficacy of currently available antibiotics. In this context, the field of pharmacometrics using quantitative model-based techniques has emerged as a powerful tool for accelerating their drug development. The “model-based” drug development helps in exploring various dosing strategies, better trial designs, and thus improves the trial success rate. Recent approval of ceftazidime-avibactam combination based on phase 2 results before the availability of phase 3 data highlights the role of population modeling in bringing the drug to market. Consequently, pharmacometrics is currently being used for major therapeutic areas in all larger pharmaceutical companies.

Regulatory agencies have also advocated the use of pharmacometrics to rationalize drug development and to support decision making. For instance, the Food and Drug Administration in the Critical Path Initiative  has recommended the quantitative model-based approaches to accelerate the drug development process while minimizing the cost. Similarly, the European Medicines Agency has endorsed modeling-based strategies for thorough investigation of pharmacology of antimicrobials. Consequently, modeling and simulation is currently being used for major therapeutic areas in all larger pharmaceutical companies.

However, pharmacometrics is still not being fully explored. The reason is the lack of skilled personnel to meet the demand in this relatively new area, which requires the background of pharmacy, statistics, and computer programming. Also, there is a need for active collaboration among the scientific groups to advance this field. One such attempt is the Drug Disease Model Resources consortium, whose objective is share knowledge of pharmacometrics worldwide. Lastly, pharmacometrics should be applied in the clinical care segment as it would constitute an important step forward to personalized medicine.

Vishnu Dutt Sharma, Ph.D., is a postdoctoral research associate at the Center for Pharmacometrics and Systems Pharmacology at the University of Florida, Orlando. His research focuses on the development and application of quantitative model-based platforms in the area of antibiotics, obesity, and cardiovascular safety. He completed his Ph.D. in Pharmaceutical Sciences in 2014 from Temple University, where he also served as the chair of their AAPS student chapter.