by Ric Slauter, PhD, DABT
Suppose a baseball team had a player whose batting average was a mere 0.0001. We can safely assume that player won’t last long.
Yet that average is the reality of drug development. Whereas 10,000 compounds might enter the discovery stage, only one is likely to survive to become a marketed medication, according to the Pharmaceutical Research and Manufacturers Association. And that’s after an investment of up to 15 years and more than $1 billion. This reality is devastating drug development pipelines and dashing hopes for patients.
With attrition rates as high as 40 percent due to drug metabolism and pharmacokinetic (DMPK) issues alone, drug developers are looking to integrate high-quality DMPK studies early in the development process. Using sophisticated technologies, these studies allow developers to accurately scale results to humans and better predict therapeutic outcomes in the clinic — meaning less attrition, lower costs, and better quality candidates moving through the pipeline.
Biopharmaceutical and biotech companies are realizing that early attention to quality DMPK efforts is a good investment. In fact, an article in Nature Reviews Drug Discovery noted the potential to reduce clinical failure rates to as low as 10 percent.
Whether DMPK studies are done in-house or by a CRO, the right expertise is crucial to ensure a successful IND submission and clinical success. The knowledge and skillset of the scientists on your team must align with the four categories where DMPK data aggregate.
- Physiochemical properties, like solubility, pKa and logP, which are the basic “what” and “how” of a compound
- Kinetics of movement through tissues and fluids
- Dynamics of interaction between the compound and proteins, nucleic acids, other drugs, and various cellular elements that result in physiologic effects
- How the drug is changed through metabolism of the drug in the body, both qualitatively and quantitatively, and how that process impacts the body
While not every step requires unique skills or technologies, many are make-or-break in the cause of lowering later-stage attrition. These include identifying metabolites in safety testing (MIST), ascertaining liability concerns, detecting production of reactive metabolites, identifying full metabolite structure, and determining covalent binding of metabolites. Done poorly, and the results of such studies might allow a compound to move forward when it shouldn’t, only to fail at a later stage after even more time and money has been wasted on a development candidate that is going nowhere.
No baseball team allows a player’s batting average to sink to drug development lows; it applies its expertise and training skill to lift the player’s performance. Likewise, successful drug developers know that applying high DMPK standards early across these four categories will improve their R&D achievements. That’s how you hit a home run in the quest for new treatments and cures.
Ric Slauter, PhD, DABT, is Senior Director of Drug Metabolism/Pharmacokinetics and Senior Principal Study Director at MPI Research. To find out how early DMPK studies can improve your success rate in drug development, contact us at firstname.lastname@example.org.