title: Widening the path and window of opportunity for FDA approval of non-vitamin K oral anticoagulant specific antidotes and reversal agents.
abstract: There remains a need for safe, immediately effective, and easy to administer antidotes for patients taking novel oral anticoagulants (NOACs) in the settings of major bleeding, need for emergency surgery, and accidental overdose. We review considerations for the successful safety and effectiveness evaluation of potential antidotes currently under development. These compounds are in expedited regulatory approval programs aimed at accelerating the preclinical and clinical evaluation and approval processes for treatments of serious conditions. We review the features of these expedited programs as well as the FDA's efforts to broadly advance the efficiency of drug development and increase the number of new compounds brought to market. The critical path initiative and regulatory science initiative have resulted in numerous successful programs to address current challenges such as a paucity of validated biomarkers and surrogate endpoints as well as unreliable animal models of toxicity. The FDA has also advocated for increased use of pharmacokinetic/pharmacodynamic modeling and adaptive trial design. These efforts foster collaboration between academia, industry and the public sector across interdisciplinary sciences and may continue to widen the pathway for NOAC-specific reversal agents and other novel compounds.
authors.affiliation: University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA. patel2sy@mail.uc.edu.
authors.forename: Sunny
authors.initials: S
authors.lastname: Patel
authors.affiliation: University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA. Dylan.Steen@uc.edu.|Division of CV Health and Disease, UC Heart, Lung, and Vascular Institute, Cardiovascular Center, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Rm 3923, Cincinnati, OH, 45267, USA. Dylan.Steen@uc.edu.
authors.forename: Dylan
authors.initials: D
authors.lastname: Steen
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000931:Antidotes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D015415:Biomarkers; D017277:Drug Approval / Q000331:legislation & jurisprudence / Q000379:methods; D006801:Humans; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000925:Anticoagulants; D000931:Antidotes; D015415:Biomarkers
keywords: Antidote; Drug approval; Novel oral anticoagulant; Reversal agent