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Andexanet alfa, the first agent shown to reverse the anticoagulant effects of rivaroxaban and apixaban, has been approved by the FDA, according to a May 3 statement from Portola Pharmaceuticals.

It is approved for use in patients treated with these factor Xa inhibitors when reversal of anticoagulation is needed because of life-threatening or uncontrolled bleeding, according to the company.

Mitchel L. Zoler/MDedge News
Dr. Stuart J. Connolly

Andexanet alfa (Andexxa, Portola) received both U.S. Orphan Drug and FDA Breakthrough Therapy designations and was approved under the FDA’s Accelerated Approval pathway.

“Today’s approval represents a significant step forward in patient care and one that the medical community has been eagerly anticipating,” said Stuart J. Connolly, MD, professor of medicine and an electrophysiologist at McMaster University in Hamilton, Ont., who is chair of the ANNEXA-4 executive committee. “Andexxa’s rapid reversal of the anticoagulating effects of rivaroxaban and apixaban will help clinicians treat life-threatening bleeds, where every minute counts,” he added in the statement.

The approval was supported by two phase 3 trials in the ANNEXA series, which showed acceptable change from baseline in anti-Factor Xa activity in healthy volunteers. But the strongest data came from interim results from ANNEXA-4, a single-arm cohort study with 227 patients who were receiving a factor Xa inhibitor and were experiencing an acute major bleeding event.

Clinicians administered andexanet alfa as a bolus followed by a 2-hour continuous infusion, with hemostatic efficacy assessed 12 hours after the start of treatment. The results showed that factor Xa inhibition fell by a median 90% for rivaroxaban and 93% for apixaban.

Andexanet alfa is a factor Xa “decoy” molecule that acts by latching onto the inhibitor molecules and thereby preventing them from interacting with actual factor Xa, but andexanet also has a short half life and hence the effect quickly reduces once treatment stops, Dr. Connelly reported at the American College of Cardiology annual meeting in March when presenting ANNEXA-4.

 

 


He noted at the time the results placed andexanet in the same ballpark for efficacy and safety as idarucizumab (Praxbind) approved in 2015 for reversing the anticoagulant dabigatran (Pradaxa)

“The expansion of available reversal agents for people prescribed newer oral anticoagulant therapies is crucial,” Randy Fenninger, chief executive officer of the National Blood Clot Alliance, said in the Portola statement. “The availability now of a reversal agent specific to rivaroxaban and apixaban expands choice and enables patients and providers to consider these treatment options with greater confidence.”

The prescribing information for andexanet states that treated patients should be monitored for signs and symptoms of arterial and venous thromboembolic events, ischemic events, and cardiac arrest. Further, anticoagulant therapy should be resumed as soon as medically appropriate following andexanet treatment to reduce thromboembolic risk.

The most common adverse reactions, occurring in at least 5% of patients, were urinary tract infections and pneumonia.

Portola intends to bring Andexxa to limited markets in early June; a broader commercial launch is anticipated in early 2019.*

The FDA is requiring a postmarketing clinical trial that randomizes patients to either andexanet or usual care. The study is scheduled to begin in 2019 and report outcomes in 2023.

*This article was updated on May 7, 2018.

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Andexanet alfa, the first agent shown to reverse the anticoagulant effects of rivaroxaban and apixaban, has been approved by the FDA, according to a May 3 statement from Portola Pharmaceuticals.

It is approved for use in patients treated with these factor Xa inhibitors when reversal of anticoagulation is needed because of life-threatening or uncontrolled bleeding, according to the company.

Mitchel L. Zoler/MDedge News
Dr. Stuart J. Connolly

Andexanet alfa (Andexxa, Portola) received both U.S. Orphan Drug and FDA Breakthrough Therapy designations and was approved under the FDA’s Accelerated Approval pathway.

“Today’s approval represents a significant step forward in patient care and one that the medical community has been eagerly anticipating,” said Stuart J. Connolly, MD, professor of medicine and an electrophysiologist at McMaster University in Hamilton, Ont., who is chair of the ANNEXA-4 executive committee. “Andexxa’s rapid reversal of the anticoagulating effects of rivaroxaban and apixaban will help clinicians treat life-threatening bleeds, where every minute counts,” he added in the statement.

The approval was supported by two phase 3 trials in the ANNEXA series, which showed acceptable change from baseline in anti-Factor Xa activity in healthy volunteers. But the strongest data came from interim results from ANNEXA-4, a single-arm cohort study with 227 patients who were receiving a factor Xa inhibitor and were experiencing an acute major bleeding event.

Clinicians administered andexanet alfa as a bolus followed by a 2-hour continuous infusion, with hemostatic efficacy assessed 12 hours after the start of treatment. The results showed that factor Xa inhibition fell by a median 90% for rivaroxaban and 93% for apixaban.

Andexanet alfa is a factor Xa “decoy” molecule that acts by latching onto the inhibitor molecules and thereby preventing them from interacting with actual factor Xa, but andexanet also has a short half life and hence the effect quickly reduces once treatment stops, Dr. Connelly reported at the American College of Cardiology annual meeting in March when presenting ANNEXA-4.

 

 


He noted at the time the results placed andexanet in the same ballpark for efficacy and safety as idarucizumab (Praxbind) approved in 2015 for reversing the anticoagulant dabigatran (Pradaxa)

“The expansion of available reversal agents for people prescribed newer oral anticoagulant therapies is crucial,” Randy Fenninger, chief executive officer of the National Blood Clot Alliance, said in the Portola statement. “The availability now of a reversal agent specific to rivaroxaban and apixaban expands choice and enables patients and providers to consider these treatment options with greater confidence.”

The prescribing information for andexanet states that treated patients should be monitored for signs and symptoms of arterial and venous thromboembolic events, ischemic events, and cardiac arrest. Further, anticoagulant therapy should be resumed as soon as medically appropriate following andexanet treatment to reduce thromboembolic risk.

The most common adverse reactions, occurring in at least 5% of patients, were urinary tract infections and pneumonia.

Portola intends to bring Andexxa to limited markets in early June; a broader commercial launch is anticipated in early 2019.*

The FDA is requiring a postmarketing clinical trial that randomizes patients to either andexanet or usual care. The study is scheduled to begin in 2019 and report outcomes in 2023.

*This article was updated on May 7, 2018.

Andexanet alfa, the first agent shown to reverse the anticoagulant effects of rivaroxaban and apixaban, has been approved by the FDA, according to a May 3 statement from Portola Pharmaceuticals.

It is approved for use in patients treated with these factor Xa inhibitors when reversal of anticoagulation is needed because of life-threatening or uncontrolled bleeding, according to the company.

Mitchel L. Zoler/MDedge News
Dr. Stuart J. Connolly

Andexanet alfa (Andexxa, Portola) received both U.S. Orphan Drug and FDA Breakthrough Therapy designations and was approved under the FDA’s Accelerated Approval pathway.

“Today’s approval represents a significant step forward in patient care and one that the medical community has been eagerly anticipating,” said Stuart J. Connolly, MD, professor of medicine and an electrophysiologist at McMaster University in Hamilton, Ont., who is chair of the ANNEXA-4 executive committee. “Andexxa’s rapid reversal of the anticoagulating effects of rivaroxaban and apixaban will help clinicians treat life-threatening bleeds, where every minute counts,” he added in the statement.

The approval was supported by two phase 3 trials in the ANNEXA series, which showed acceptable change from baseline in anti-Factor Xa activity in healthy volunteers. But the strongest data came from interim results from ANNEXA-4, a single-arm cohort study with 227 patients who were receiving a factor Xa inhibitor and were experiencing an acute major bleeding event.

Clinicians administered andexanet alfa as a bolus followed by a 2-hour continuous infusion, with hemostatic efficacy assessed 12 hours after the start of treatment. The results showed that factor Xa inhibition fell by a median 90% for rivaroxaban and 93% for apixaban.

Andexanet alfa is a factor Xa “decoy” molecule that acts by latching onto the inhibitor molecules and thereby preventing them from interacting with actual factor Xa, but andexanet also has a short half life and hence the effect quickly reduces once treatment stops, Dr. Connelly reported at the American College of Cardiology annual meeting in March when presenting ANNEXA-4.

 

 


He noted at the time the results placed andexanet in the same ballpark for efficacy and safety as idarucizumab (Praxbind) approved in 2015 for reversing the anticoagulant dabigatran (Pradaxa)

“The expansion of available reversal agents for people prescribed newer oral anticoagulant therapies is crucial,” Randy Fenninger, chief executive officer of the National Blood Clot Alliance, said in the Portola statement. “The availability now of a reversal agent specific to rivaroxaban and apixaban expands choice and enables patients and providers to consider these treatment options with greater confidence.”

The prescribing information for andexanet states that treated patients should be monitored for signs and symptoms of arterial and venous thromboembolic events, ischemic events, and cardiac arrest. Further, anticoagulant therapy should be resumed as soon as medically appropriate following andexanet treatment to reduce thromboembolic risk.

The most common adverse reactions, occurring in at least 5% of patients, were urinary tract infections and pneumonia.

Portola intends to bring Andexxa to limited markets in early June; a broader commercial launch is anticipated in early 2019.*

The FDA is requiring a postmarketing clinical trial that randomizes patients to either andexanet or usual care. The study is scheduled to begin in 2019 and report outcomes in 2023.

*This article was updated on May 7, 2018.

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