Preclinical and clinical studies in the drug development process of European Medicines Agency-approved non-HIV antiviral agents: a narrative review.

Background: Viral diseases represent a substantial global health challenge, necessitating the urgent development of effective antiviral medications.

Objectives: This review aims to present a thorough examination of systemic antiviral drugs approved by the European Medicines Agency (EMA) since its founding, excluding those targeting HIV, with a focus on preclinical and clinical studies in the drug development process.

Sources: Data was extracted from the European Public Assessment Reports and Summary of Product Characteristics issued by the EMA.

Content: In total, 21 currently approved agents were analysed with a focus on preclinical and clinical studies. The majority of substances have been approved for hepatitis C (38%) and B (19%) followed by influenza and SARS-CoV-2 (14% and 10%, respectively). A smaller subset obtained approval for the indications of hepatitis D, cytomegalovirus, and pox viruses. As for preclinical studies, heterogeneity in the methods used for efficacy studies was observed, which is at least partly explained by the diverse nature of viruses and their hosts and the lack of general guidelines for antiviral pharmacokinetics and pharmacodynamics studies by the EMA. Clinical studies varied in sample sizes, ranging from a few hundred to several thousand patients. Many antiviral agents have a high potential for cytochrome P450 (CYP) and other enzyme interactions, resulting in the need for a high number of drug-drug interaction studies. Special market authorizations are available, including conditional approval for urgently required drugs such as nirmatrelvir/ritonavir for the treatment of COVID-19, and authorization under exceptional circumstances when comprehensive data cannot be provided, as seen with tecovirimat for pox viruses.

Implications: Streamlining the drug development process of antiviral substances and providing more guidelines would be crucial given the ongoing demand for effective treatment options for existing and new viral diseases.