Benefit-risk assessment for brincidofovir for the treatment of smallpox: U.S. Food and Drug Administration's Evaluation

Kirk Chan-Tack; Patrick Harrington; Timothy Bensman; Su-Young Choi; Eric Donaldson; Julian O'Rear; David McMillan; Laine Myers; Mark Seaton; Hanan Ghantous; Yu Cao; Thamban Valappil; Debra Birnkrant; Kimberly Struble

doi:10.1016/j.antiviral.2021.105182

Benefit-risk assessment for brincidofovir for the treatment of smallpox: U.S. Food and Drug Administration's Evaluation

Antiviral Res. 2021 Nov:195:105182. doi: 10.1016/j.antiviral.2021.105182. Epub 2021 Sep 25.

Authors

Affiliations

¹ Division of Antivirals, Office of Infectious Diseases, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. Electronic address: Kirk.Chan-Tack@fda.hhs.gov.
² Division of Antivirals, Office of Infectious Diseases, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
³ Office of Translational Sciences, Office of Clinical Pharmacology, Division of Clinical Pharmacology IV, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
⁴ Division of Pharmacology/Toxicology for Infectious Diseases, Office of Infectious Diseases, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
⁵ Division of Biometrics IV, Office of Biostatistics, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.

PMID: 34582915
DOI: 10.1016/j.antiviral.2021.105182

Abstract

The development and approval of brincidofovir for the treatment of smallpox, a disease that was eradicated from the world over 40 years ago, has resulted in the second antiviral approved via the Medical Countermeasure Initiative (MCMi) to combat this disease. Approval of brincidofovir required a unique regulatory approach based on the FDA Animal Rule, and development was supported by many years of research and collaboration among academic investigators, the pharmaceutical industry and multiple government agencies. This article summarizes the FDA regulatory pathway and describes the challenges involved.

Keywords: Animal rule; Antiviral; Smallpox; Variola virus.

Published by Elsevier B.V.

Publication types

Review

MeSH terms

Animals
Antiviral Agents / therapeutic use*
Cytosine / analogs & derivatives*
Cytosine / therapeutic use
Disease Eradication
Disease Models, Animal
Drug Approval*
Humans
Organophosphonates / therapeutic use*
Risk Assessment
Smallpox / drug therapy*
Treatment Outcome
United States
United States Food and Drug Administration

Substances

Antiviral Agents
Organophosphonates
brincidofovir
Cytosine