The process of drug discovery and the Yin/Yang of small-molecule/biotech option

Abstract

Until the mid 90ties of last century, talking about drug discovery and development was essentially referred to the process of discovery and development of small-molecule chemical entities. All the language, common procedures and technicalities were inherent to this setting; concepts such as drug design, hit and lead compounds, high-throughput screening were referring to the typical mode of investigating and selecting small-molecule candidates through pre-clinical development. At that time, the arrival of the first biotech drugs has markedly changed the landscape, requiring a completely new approach to pre-clinical development. Issues related to drug-receptor interaction or to the selection from a huge number of candidates were obviously simplified to a minimum compared to the small-molecule setting. Conversely, the pharmaceutical development of biotech drugs showed far higher complexity, and the overall high complexity of industrial production initially represented a major issue to justify the high costs of biotech drugs.Besides, the technical impossibility to make ‘generics’ of biotech drugs was another strong reason driving Pharma companies toward the development of biotech drugs. Thus, in the beginning the early development phases of small-molecules or biotech drugs really stood as two distant planets. However, by the time such initial distances have been progressively reduced. From the biotech site, the technique of phage-display library scanning and similar approaches made the selection of biotech lead compounds resembling more closely what happens with small molecules; also the complexities and high costs of pharmaceutical production have progressively reduced their impact. On the other site, the impressive progresses of basic knowledge on the human kinome and other relevant fields of molecular and cellular biology made possible that today we have small-molecule drugs targeting the same pathologies once specifically targeted by biotech drugs, MoAbs in particular.Another factor (albeit not related to drug development) with an important role in reducing distances between small-molecule and biotech drugs has been the novel approach to estimate the value of drugs, and therefore their prices. Since nowadays the major drive fixing the value (and costs) of new drugs is the added value for human health, any difference related to the costs of production has been greatly reduced, and we have today several high-cost small molecules along with their sibling biotech drugs.Last but not least, biotech drugs can be ‘copied’ as well, since we now have biosimilar drugs, although the pathway to develop copies of biotech drugs remains steeper compared to that leading to the equivalents of small-molecule drugs.