Drug development is like climbing a well-defined heavily regulated “ladder”. This ladder has and will always rightly hold the safety of patients subjected to experimental therapies as its number one priority. Each of the steps are clearly defined, and whilst some may intertwine generally include:
- Pre-clinical development,comprisingex-vivo experiments designed to test a scientific hypothesis and chemical product characteristics, as well as in-vivo studies to characterize toxicity, pharmacology, and possible clinical efficacy
- Clinical studies, including initial safety assessment (phase 1), dose and regimen determination as well as directional efficacy (phase 2), as well as conclusive proof of safety and efficacy (phase 3)
The overall process of developing a new medication takes many years and all too often above a decade.
The Covid-19 pandemic renders drug development resembling a ladder with a rung missing.
Initially and despite an evident absence of preclinical models for the new disease, the drug development world fractured into two schools of thinking:
- A “classical” school, that was expecting several years to pass until a new vaccine could be developed, in the traditional way going from candidate identification and pre-clinical development over staged-gated testing in humans
- A “pragmatic” school, that advocated exploring the possible benefit of products developed for another purpose against the new disease
When the global public discussion about Covid-19 emerged earlier this year and policy, research and industry set out on an unprecedentedly urgent quest to resolve what would become the most economically impactful disease in modern history, the “pragmatic” school was broadly deemed a rogue way of thinking.
Now, months later, the world has witnessed the US regulatory authority’s emergency use authorization for a product developed the latter way, Gilead’s remdesivir which initially aimed at Ebola and Marburg virus infections but was never actually approved – however, had shown some indications of efficacy against a range of RNA viruses and a characterized safety profile that led to its investigation in Covid-19 patients.
In a situation of crisis and urgency, established processes and thinking need rapid, forceful and, ideally, structured considerate adaptation. Whilst certainly remaining within the boundaries of safety and ethicality, the pragmatism and vigor in which Covid-19 treatments are now being developed may forever change the rungs of the “ladder” that constitutes the development of therapeutics.