COVID-19 drug development is the research process to develop preventative therapeutic prescription drugs that would alleviate the severity of coronavirus disease 2019 (COVID-19). From early 2020 through 2021, several hundred drug companies, biotechnology firms, university research groups, and health organizations were developing therapeutic candidates for COVID-19 disease in various stages of preclinical or clinical research (506 total candidates in April 2021), with 419 potential COVID-19 drugs in clinical trials, as of April 2021.
As early as March 2020, the World Health Organization (WHO), European Medicines Agency (EMA), US Food and Drug Administration (FDA), and the Chinese government and drug manufacturers were coordinating with academic and industry researchers to speed development of vaccines, antiviral drugs, and post-infection therapies. The International Clinical Trials Registry Platform of the WHO recorded 536 clinical studies to develop post-infection therapies for COVID-19 infections, with numerous established antiviral compounds for treating other infections under clinical research to be repurposed.
In March 2020, the WHO initiated the "SOLIDARITY Trial" in 10 countries, enrolling thousands of people infected with COVID-19 to assess treatment effects of four existing antiviral compounds with the most promise of efficacy. A dynamic, systematic review was established in April 2020 to track the progress of registered clinical trials for COVID-19 vaccine and therapeutic drug candidates.
Drug development is a multistep process, typically requiring more than five years to assure safety and efficacy of the new compound. Several national regulatory agencies, such as the EMA and the FDA, approved procedures to expedite clinical testing. By June 2021, dozens of potential post-infection therapies were in the final stage of human testing – phase III–IV clinical trials.
Background
Drug development is the process of bringing a new infectious disease vaccine or therapeutic drug to the market once a lead compound has been identified through the process of drug discovery. It includes laboratory research on microorganisms and animals, filing for regulatory status, such as via the FDA, for an investigational new drug to initiate clinical trials on humans, and may include the step of obtaining regulatory approval with a new drug application to market the drug. The entire process – from concept through preclinical testing in the laboratory to clinical trial development, including Phase I–III trials – to approved vaccine or drug normally takes more than a decade.
The term "preclinical research" is defined by laboratory studies in vitro and in vivo, indicating a beginning stage for development of a preventative vaccine, antiviral or other post-infection therapies, such as experiments to determine effective doses and toxicity in animals, before a candidate compound is advanced for safety and efficacy evaluation in humans. To complete the preclinical stage of drug development – then be tested for safety and efficacy in an adequate number of people infected with COVID-19 (hundreds to thousands in different countries) – is a process likely to require 1–2 years for COVID-19 therapies, according to several reports in early 2020. Despite these efforts, the success rate for drug candidates to reach eventual regulatory approval through the entire drug development process for treating infectious diseases is only 19%.
Phase I trials test primarily for safety and preliminary dosing in a few dozen healthy subjects, while Phase II trials – following success in Phase I – evaluate therapeutic efficacy against the COVID-19 disease at ascending dose levels (efficacy based on biomarkers), while closely evaluating possible adverse effects of the candidate therapy (or combined therapies), typically in hundreds of people. A common trial design for Phase II studies of possible COVID-19 drugs is randomized, placebo-controlled, blinded, and conducted at multiple sites, while determining more precise, effective doses and monitoring for adverse effects.
The success rate for Phase II trials to advance to Phase III (for all diseases) is about 31%, and for infectious diseases specifically, about 43%. Depending on its duration (longer more expensive) – typically a period of several months to two years – an average-length Phase II trial costs million (2013 dollars, including preclinical and Phase I costs). Successful completion of a Phase II trial does not reliably forecast that a candidate drug will be successful in Phase III research.