Making a New Medicine Part 1: Discovery and Development

The discovery and development of a new medicine is a complex and lengthy process. Many founders begin searching for a new therapy without understanding these details. In my experience, most of the public views drug development as “the news reports that scientists show it works in a mouse, so my doctor will be able to write a prescription next week.” In an educational effort for summer break, I offer this four-part series describing the different stages of drug development, which are applicable in all regulatory jurisdictions.

The process of finding a new medicine starts with discovery research. The aim of these studies is to clearly identify the hypothetical mechanisms for the target disease state, develop relevant mechanistic models for testing potential therapeutics, and find active drugs (either chemical or biological) in the model. This is the most challenging part of pharmaceutical research. The proposed mechanism for drug action must be understood well enough to create a model system that demonstrates a direct connection between the presence of a drug and a relevant change in the system. This system change is often referred to as the target, and increased confidence in a target is established when multiple model systems (for example, published studies supporting the mechanism, cell lines expressing a receptor, animal models, or measurable genetic variants) support the mechanism. Once a target has been defined, active drugs must be found by various screening methods (sampling in an existing compound library, computer modeling of the molecular target, or brute force measurements of many compound structures), which frequently evaluate thousands of individual compounds before finding a ‘hit’ which shows the desired activity in the target. Many programs fail to find a hit with sufficient activity for development and unique enough to permit filing a patent even after screening thousands of compounds. When a hit is found, analog compounds are created and screened to find a lead compound and at least one backup acceptable for preclinical development. Compounds are also frequently screened in parallel for properties that are known to make them easier to develop as a medicine. These are often referred to as ‘druggable’ properties. The entire process can take years and occurs before the clock starts on patent exclusivity for a medicine.

Learn More

Readers interested in more details on discovery research will find this 2011 review article published by Hughes et al. in the British Journal of Pharmacology, which presents an accessible explanation of the drug discovery process. [1] More details on preclinical development may be found in this 2009 article by Steinmetz and Speck, which focuses on therapies in neurodegenerative diseases. [2]

Part 2 of this series provides an overview of the clinical trial process and a closer look at the first two trial phases.

As always, contact me any time if you have questions.

References

[1] Hughes, J. P., Rees, S., Kalindjian, S. B., & Philpott, K. L. (2011). Principles of early drug discovery.?British journal of pharmacology,?162(6), 1239–1249. https://doi.org/10.1111/j.1476-5381.2010.01127.x

[2] Steinmetz, K. L., & Spack, E. G. (2009). The basics of preclinical drug development for neurodegenerative disease indications. BMC Neurology, 9(1), S2. doi:10.1186/1471-2377-9-S1-S2?