FDA Advisory Committee Meeting

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel supported approval of cangrelor, a short-acting, intravenous antiplatelet drug, for use in patients undergoing percutaneous coronary intervention, with precautions that it not be used widely or indiscriminately.

At a meeting on April 15, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 9-2, with one abstention, that cangrelor should be approved as an adjunct to PCI “for reducing the periprocedural thrombotic events, such as MI, stent thrombosis, and ischemia-driven revascularization.” The proposed indication includes the statement that use is for patients undergoing PCI “who have not received an oral P2Y₁₂ inhibitor prior to the PCI procedure and in whom oral therapy with P2Y₁₂ inhibitors is not feasible or desirable.”

Cangrelor, a P2Y₁₂ receptor inhibitor, has a half-life of 3-6 minutes, and platelet function completely returns to normal within 1 hour of stopping the infusion, according to the product’s sponsor, the Medicines Company.

The vote was based on analyses of revised endpoints of the data from the CHAMPION PHOENIX study, which compared cangrelor to clopidogrel in more than 11,000 patients undergoing PCI. The same panel voted 7-2 against approval in February 2014, for reasons that included doubts about the clinical consequences of some of the endpoints of the trial.

At the request of the FDA, the company reanalyzed the data, dropping intraprocedural stent thrombosis and MIs that did not meet the SCAI (Society for Cardiovascular Angiography Interventions) criteria for a clinically relevant MI from the primary endpoint. At 48 hours, 1.4% of those in the cangrelor arm met this revised endpoint, vs. 2.1% of those in the clopidogrel arm, for an odds ratio of 0.69 (P = .011). Most of the panel agreed that these analyses showed the drug had a beneficial effect.

Deaths and serious adverse events were similar between cangrelor and clopidogrel, but bleeding events were more common among patients treated with cangrelor, according to the company. A risk-benefit analysis, which took into account bleeding events, provided by the FDA concluded that the “benefit of cangrelor is small, but the risk is smaller.”

“There’s a great responsibility that this gets used appropriately and [is] not overused,” said Dr. James de Lemos, who voted against approval at the last meeting but voted for approval at this meeting. Dr. de Lemos, distinguished chair in cardiology and professor of medicine at the University of Texas Southwestern Medical Center, Dallas, said that his concerns about the robustness of the primary endpoint that had been “mostly addressed” by the FDA’s and company’s analyses.

However, he added that he remained concerned by the very narrow clinical benefit of the drug "relative to the risks and relative to what I worry will be the potential use of the drug.”

”What I would hope is that this drug is used very selectively and very narrowly in circumstances where P2Y₁₂ inhibitors cannot be used appropriately,” he commented. “If it is used broadly and indiscriminately, it will not only be expensive but it [also] will expose low-risk patients to unnecessary bleeding, some of which can be quite substantial.”

The FDA usually follows the recommendations of its advisory panels. The members of the panel had no relevant disclosures.

[email protected]

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel supported approval of cangrelor, a short-acting, intravenous antiplatelet drug, for use in patients undergoing percutaneous coronary intervention, with precautions that it not be used widely or indiscriminately.

At a meeting on April 15, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 9-2, with one abstention, that cangrelor should be approved as an adjunct to PCI “for reducing the periprocedural thrombotic events, such as MI, stent thrombosis, and ischemia-driven revascularization.” The proposed indication includes the statement that use is for patients undergoing PCI “who have not received an oral P2Y₁₂ inhibitor prior to the PCI procedure and in whom oral therapy with P2Y₁₂ inhibitors is not feasible or desirable.”

Cangrelor, a P2Y₁₂ receptor inhibitor, has a half-life of 3-6 minutes, and platelet function completely returns to normal within 1 hour of stopping the infusion, according to the product’s sponsor, the Medicines Company.

The vote was based on analyses of revised endpoints of the data from the CHAMPION PHOENIX study, which compared cangrelor to clopidogrel in more than 11,000 patients undergoing PCI. The same panel voted 7-2 against approval in February 2014, for reasons that included doubts about the clinical consequences of some of the endpoints of the trial.

At the request of the FDA, the company reanalyzed the data, dropping intraprocedural stent thrombosis and MIs that did not meet the SCAI (Society for Cardiovascular Angiography Interventions) criteria for a clinically relevant MI from the primary endpoint. At 48 hours, 1.4% of those in the cangrelor arm met this revised endpoint, vs. 2.1% of those in the clopidogrel arm, for an odds ratio of 0.69 (P = .011). Most of the panel agreed that these analyses showed the drug had a beneficial effect.

Deaths and serious adverse events were similar between cangrelor and clopidogrel, but bleeding events were more common among patients treated with cangrelor, according to the company. A risk-benefit analysis, which took into account bleeding events, provided by the FDA concluded that the “benefit of cangrelor is small, but the risk is smaller.”

“There’s a great responsibility that this gets used appropriately and [is] not overused,” said Dr. James de Lemos, who voted against approval at the last meeting but voted for approval at this meeting. Dr. de Lemos, distinguished chair in cardiology and professor of medicine at the University of Texas Southwestern Medical Center, Dallas, said that his concerns about the robustness of the primary endpoint that had been “mostly addressed” by the FDA’s and company’s analyses.

However, he added that he remained concerned by the very narrow clinical benefit of the drug "relative to the risks and relative to what I worry will be the potential use of the drug.”

”What I would hope is that this drug is used very selectively and very narrowly in circumstances where P2Y₁₂ inhibitors cannot be used appropriately,” he commented. “If it is used broadly and indiscriminately, it will not only be expensive but it [also] will expose low-risk patients to unnecessary bleeding, some of which can be quite substantial.”

The FDA usually follows the recommendations of its advisory panels. The members of the panel had no relevant disclosures.

[email protected]

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel supported approval of cangrelor, a short-acting, intravenous antiplatelet drug, for use in patients undergoing percutaneous coronary intervention, with precautions that it not be used widely or indiscriminately.

At a meeting on April 15, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 9-2, with one abstention, that cangrelor should be approved as an adjunct to PCI “for reducing the periprocedural thrombotic events, such as MI, stent thrombosis, and ischemia-driven revascularization.” The proposed indication includes the statement that use is for patients undergoing PCI “who have not received an oral P2Y₁₂ inhibitor prior to the PCI procedure and in whom oral therapy with P2Y₁₂ inhibitors is not feasible or desirable.”

Cangrelor, a P2Y₁₂ receptor inhibitor, has a half-life of 3-6 minutes, and platelet function completely returns to normal within 1 hour of stopping the infusion, according to the product’s sponsor, the Medicines Company.

The vote was based on analyses of revised endpoints of the data from the CHAMPION PHOENIX study, which compared cangrelor to clopidogrel in more than 11,000 patients undergoing PCI. The same panel voted 7-2 against approval in February 2014, for reasons that included doubts about the clinical consequences of some of the endpoints of the trial.

At the request of the FDA, the company reanalyzed the data, dropping intraprocedural stent thrombosis and MIs that did not meet the SCAI (Society for Cardiovascular Angiography Interventions) criteria for a clinically relevant MI from the primary endpoint. At 48 hours, 1.4% of those in the cangrelor arm met this revised endpoint, vs. 2.1% of those in the clopidogrel arm, for an odds ratio of 0.69 (P = .011). Most of the panel agreed that these analyses showed the drug had a beneficial effect.

Deaths and serious adverse events were similar between cangrelor and clopidogrel, but bleeding events were more common among patients treated with cangrelor, according to the company. A risk-benefit analysis, which took into account bleeding events, provided by the FDA concluded that the “benefit of cangrelor is small, but the risk is smaller.”

“There’s a great responsibility that this gets used appropriately and [is] not overused,” said Dr. James de Lemos, who voted against approval at the last meeting but voted for approval at this meeting. Dr. de Lemos, distinguished chair in cardiology and professor of medicine at the University of Texas Southwestern Medical Center, Dallas, said that his concerns about the robustness of the primary endpoint that had been “mostly addressed” by the FDA’s and company’s analyses.

However, he added that he remained concerned by the very narrow clinical benefit of the drug "relative to the risks and relative to what I worry will be the potential use of the drug.”

”What I would hope is that this drug is used very selectively and very narrowly in circumstances where P2Y₁₂ inhibitors cannot be used appropriately,” he commented. “If it is used broadly and indiscriminately, it will not only be expensive but it [also] will expose low-risk patients to unnecessary bleeding, some of which can be quite substantial.”

The FDA usually follows the recommendations of its advisory panels. The members of the panel had no relevant disclosures.

[email protected]