Plenge Lab
Date posted: July 28, 2016 | Author: | No Comments »

Categories: Drug Discovery

I know it may seem strange that I am commenting on my own commentary. While writing the Science Translational Medicine (STM) article (here, here), I wanted to focus on a clear vision for improving R&D productivity via integrating human biology, therapeutic modulation, pharmacodynamics biomarkers, and proof-of-concept clinical trials (see Figure 1 of the manuscript, also above). Too often, these four key concepts get lost amongst the many steps in drug development.  I won’t revisit these concepts here, as I encourage you to read the article itself.

However, there is much more to R&D productivity than just these four concepts, and the purpose of this blog is to broaden the perspective piece a bit.

[Disclaimer: I am a Merck/MSD employee. The opinions I am expressing are my own and do not necessarily represent the position of my employer.]

1. Drug discovery should always start with the patient. Every drug discovery journey must begin with a clear definition of the unmet medical need. As a former practicing rheumatologist, I always try to keep in mind the questions that a patient would ask me: “Why did I develop this disease?” “Will I respond to this medication?” “What is my prognosis?” “Will I ever be cured?“

These questions are also important in the context of the translational medicine model proposed in the STM article.…

Read full article...


Date posted: July 24, 2016 | Author: | No Comments »

Categories: Drug Discovery Embedded Genomics

Here are my thoughts on the Discussion Paper by Bernard H. Munos and John J. Orloff, “Disruptive Innovation and Transformation of the Drug Discovery and Development Enterprise” (download pdf here). This blog won’t make much sense if read out-of-context. Thus, I recommend reading the Discussion Paper itself, and using this blog as a companion guide at the completion of each section.

[Disclaimer: I am a Merck/MSD employee. The opinions I am expressing are my own and do not necessarily represent the position of my employer.]

STRENGTHS AND WEAKNESSES OF THE CURRENT INDUSTRY MODEL

In the near-term (10-years), I suspect that the pharma model of late development and commercialization will likely persist, as the cost and complexity of getting a drug approved is difficult by other mechanisms. Over time, however, new ways of performing late-stage trials will likely evolve. Drugs that are today in the early R&D pipeline will drive this evolution. If drugs look like they do today, dominated by small molecules and biologics with high probability of failure in Phase II/III, then the current model will likely continue with incremental improvements in efficiency. However, if new therapeutic modalities emerge (CRISPR, mRNA, microbiome, etc) and/or the probability of success in Phase II/III improves substantially, then the model of late development and commercialization will be forced to evolve, too.…

Read full article...