Ticagrelor Okayed, But With High-Dose Aspirin Warning

The Food and Drug Administration has approved Brilinta (ticagrelor), but the antiplatelet drug will carry a boxed warning that taking the agent with more than 100 mg/day of aspirin decreases its effectiveness, thus ending the saga of the poor performing North American subgroup in the PLATO trial.

The approval had previously been held up by the mysteriously poor performance of North American patients in PLATO (A Comparison of AZD6140 and Clopidogrel in Patients With Acute Coronary Syndrome), the 43-country, 18,624-patient pivotal trial. The subgroup experienced a nonsignificant 27% increased risk, whereas non-U.S. results showed a significant 19% risk reduction. The company has laid the discrepancy to the difference in aspirin prescribing practice, but FDA reviewers, although swayed by the efficacy of the drug, didn’t buy into this theory and asked for additional analyses of PLATO in a December 2010 "complete response" letter.

The FDA announced its approval of the blood thinner late on July 20. Brilinta, manufactured by AstraZeneca, is cleared to reduce cardiovascular death and heart attack in patients with acute coronary syndromes.

In clinical trials, Brilinta was more effective than Bristol-Myers Squibb/Sanofi’s Plavix (clopidogrel), "but that advantage was seen with aspirin maintenance doses of 75 to 100 mg once daily," Dr. Norman Stockbridge, director of the Center for Drug Evaluation and Research’s Cardiovascular and Renal Products Division, pointed out in the agency’s announcement.

The distinction between the maintenance dose and the limitation in the labeling is an important one. In the United States, physicians tend to prescribe high-dose aspirin more often than low-dose aspirin. That challenge will be partially addressed through the REMS (Risk Evaluation and Mitigation Strategy) that the FDA attached to the approval. The REMS requires the company to conduct educational outreach to alert physicians about the risk of using higher doses of aspirin, as well as provide a MedGuide to inform patients.

The educational efforts will be key to avoiding bleeding, which is already a known hazard of the class. It may also give physicians a reason not to switch their patients.

AstraZeneca said that in most cases, it expects 81 mg aspirin to be used. The company said it will focus for the next 12 months on the process of working with hospital formularies, protocol committees, and government and managed care reimbursement bodies, all of which are necessary steps to ensure that Brilinta will be adopted.

With this approval, ticagrelor is now available in 39 countries and is reimbursed in 7, AstraZeneca noted.

This coverage is provided courtesy of "The Pink Sheet." Elsevier Global Medical News and "The Pink Sheet" are owned by Elsevier.

The Food and Drug Administration has approved Brilinta (ticagrelor), but the antiplatelet drug will carry a boxed warning that taking the agent with more than 100 mg/day of aspirin decreases its effectiveness, thus ending the saga of the poor performing North American subgroup in the PLATO trial.

The approval had previously been held up by the mysteriously poor performance of North American patients in PLATO (A Comparison of AZD6140 and Clopidogrel in Patients With Acute Coronary Syndrome), the 43-country, 18,624-patient pivotal trial. The subgroup experienced a nonsignificant 27% increased risk, whereas non-U.S. results showed a significant 19% risk reduction. The company has laid the discrepancy to the difference in aspirin prescribing practice, but FDA reviewers, although swayed by the efficacy of the drug, didn’t buy into this theory and asked for additional analyses of PLATO in a December 2010 "complete response" letter.

The FDA announced its approval of the blood thinner late on July 20. Brilinta, manufactured by AstraZeneca, is cleared to reduce cardiovascular death and heart attack in patients with acute coronary syndromes.

In clinical trials, Brilinta was more effective than Bristol-Myers Squibb/Sanofi’s Plavix (clopidogrel), "but that advantage was seen with aspirin maintenance doses of 75 to 100 mg once daily," Dr. Norman Stockbridge, director of the Center for Drug Evaluation and Research’s Cardiovascular and Renal Products Division, pointed out in the agency’s announcement.

The distinction between the maintenance dose and the limitation in the labeling is an important one. In the United States, physicians tend to prescribe high-dose aspirin more often than low-dose aspirin. That challenge will be partially addressed through the REMS (Risk Evaluation and Mitigation Strategy) that the FDA attached to the approval. The REMS requires the company to conduct educational outreach to alert physicians about the risk of using higher doses of aspirin, as well as provide a MedGuide to inform patients.

The educational efforts will be key to avoiding bleeding, which is already a known hazard of the class. It may also give physicians a reason not to switch their patients.

AstraZeneca said that in most cases, it expects 81 mg aspirin to be used. The company said it will focus for the next 12 months on the process of working with hospital formularies, protocol committees, and government and managed care reimbursement bodies, all of which are necessary steps to ensure that Brilinta will be adopted.

With this approval, ticagrelor is now available in 39 countries and is reimbursed in 7, AstraZeneca noted.

This coverage is provided courtesy of "The Pink Sheet." Elsevier Global Medical News and "The Pink Sheet" are owned by Elsevier.

The Food and Drug Administration has approved Brilinta (ticagrelor), but the antiplatelet drug will carry a boxed warning that taking the agent with more than 100 mg/day of aspirin decreases its effectiveness, thus ending the saga of the poor performing North American subgroup in the PLATO trial.

The approval had previously been held up by the mysteriously poor performance of North American patients in PLATO (A Comparison of AZD6140 and Clopidogrel in Patients With Acute Coronary Syndrome), the 43-country, 18,624-patient pivotal trial. The subgroup experienced a nonsignificant 27% increased risk, whereas non-U.S. results showed a significant 19% risk reduction. The company has laid the discrepancy to the difference in aspirin prescribing practice, but FDA reviewers, although swayed by the efficacy of the drug, didn’t buy into this theory and asked for additional analyses of PLATO in a December 2010 "complete response" letter.

The FDA announced its approval of the blood thinner late on July 20. Brilinta, manufactured by AstraZeneca, is cleared to reduce cardiovascular death and heart attack in patients with acute coronary syndromes.

In clinical trials, Brilinta was more effective than Bristol-Myers Squibb/Sanofi’s Plavix (clopidogrel), "but that advantage was seen with aspirin maintenance doses of 75 to 100 mg once daily," Dr. Norman Stockbridge, director of the Center for Drug Evaluation and Research’s Cardiovascular and Renal Products Division, pointed out in the agency’s announcement.

The distinction between the maintenance dose and the limitation in the labeling is an important one. In the United States, physicians tend to prescribe high-dose aspirin more often than low-dose aspirin. That challenge will be partially addressed through the REMS (Risk Evaluation and Mitigation Strategy) that the FDA attached to the approval. The REMS requires the company to conduct educational outreach to alert physicians about the risk of using higher doses of aspirin, as well as provide a MedGuide to inform patients.

The educational efforts will be key to avoiding bleeding, which is already a known hazard of the class. It may also give physicians a reason not to switch their patients.

AstraZeneca said that in most cases, it expects 81 mg aspirin to be used. The company said it will focus for the next 12 months on the process of working with hospital formularies, protocol committees, and government and managed care reimbursement bodies, all of which are necessary steps to ensure that Brilinta will be adopted.

With this approval, ticagrelor is now available in 39 countries and is reimbursed in 7, AstraZeneca noted.

This coverage is provided courtesy of "The Pink Sheet." Elsevier Global Medical News and "The Pink Sheet" are owned by Elsevier.