Victor L Serebruany1. 1. HeartDrug™ Research Laboratories, Johns Hopkins University, Towson, MD 21204, USA. heartdrug@aol.com
Abstract
CONTEXT: On July 20, 2011, the Food and Drug Administration (FDA) approved ticagrelor (Brilinta™) for use during acute coronary syndromes. The drug labeling includes a 'black box' warning for bleeding risks, conventional for antithrombotics, and a unique warning that higher than 100 mg/daily maintenance treatment with aspirin may reduce ticagrelor effectiveness. The approval was granted following ticagrelor secondary reviews, and review of complete response by FDA officials. OBJECTIVE: To summarize the recommendations of different FDA reviewers, and their impact on drug approval. DESIGN, SETTING, AND PATIENTS: Review of the Platelet Inhibition and Clinical Outcomes (PLATO) trial comparing the efficacy of ticagrelor versus standard care treatment with clopidogrel. Patients (n = 18,624) with moderate- to high-risk acute coronary syndromes undergoing coronary intervention or being medically managed were randomized to ticagrelor (180-mg loading dose followed by 90 mg twice daily thereafter) or clopidogrel (300-600-mg loading dose followed by 75 mg once daily) for 6-12 months. RESULTS: The facts outlined in official reviews suggest that ticagrelor has been approved despite objections from both clinical primary reviewers assessing drug efficacy and safety. In addition, the statistical reviewer and cross-discipline team leader also recommended against approval. The putative grounds for their concerns were retrieved from the public FDA records and are briefly outlined here.
CONTEXT: On July 20, 2011, the Food and Drug Administration (FDA) approved ticagrelor (Brilinta™) for use during acute coronary syndromes. The drug labeling includes a 'black box' warning for bleeding risks, conventional for antithrombotics, and a unique warning that higher than 100 mg/daily maintenance treatment with aspirin may reduce ticagrelor effectiveness. The approval was granted following ticagrelor secondary reviews, and review of complete response by FDA officials. OBJECTIVE: To summarize the recommendations of different FDA reviewers, and their impact on drug approval. DESIGN, SETTING, AND PATIENTS: Review of the Platelet Inhibition and Clinical Outcomes (PLATO) trial comparing the efficacy of ticagrelor versus standard care treatment with clopidogrel. Patients (n = 18,624) with moderate- to high-risk acute coronary syndromes undergoing coronary intervention or being medically managed were randomized to ticagrelor (180-mg loading dose followed by 90 mg twice daily thereafter) or clopidogrel (300-600-mg loading dose followed by 75 mg once daily) for 6-12 months. RESULTS: The facts outlined in official reviews suggest that ticagrelor has been approved despite objections from both clinical primary reviewers assessing drug efficacy and safety. In addition, the statistical reviewer and cross-discipline team leader also recommended against approval. The putative grounds for their concerns were retrieved from the public FDA records and are briefly outlined here.
Authors: Nishank Jain; Bradley C Martin; Junqiang Dai; Milind A Phadnis; Layth Al-Hindi; Theresa I Shireman; S Susan Hedayati; Rafia S Rasu; Jawahar L Mehta Journal: Kidney360 Date: 2022-05-18