FDA News

Antidote for certain direct oral anticoagulants receives FDA approval

Stuart J. Connolly

Portola Pharmaceuticals announced the FDA approved andexanet alfa, the first antidote indicated for patients treated with rivaroxaban and apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

According to a press release from Portola, the approval of andexanet alfa (Andexxa) follows the results of the phase 3 ANNEXA studies, recently published in The New England Journal of Medicine.

As previously reported by Cardiology Today, the ANNEXA studies reported the highest rate of hemostatic efficacy for any anticoagulant reversal agent to date.

The antidote is approved for reversal of the effects of two Factor Xa inhibitors, apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) and rivaroxaban (Xarelto, Janssen), which are often prescribed to patients with nonvalvular atrial fibrillation requiring stroke protection and to patients at risk for venous thromboembolism.

“The unmet medical need and number of patients admitted to the hospital with Factor Xa-related bleeding is significant and it continues to grow,” Bill Lis, CEO of Portola, said during a telebriefing. “[There were] more than 117,000 hospital admissions in 2016 alone.”

According to a press release from Portola, Andexxa received both U.S. Orphan Drug and FDA Breakthrough Therapy designations and was approved under the FDA's Accelerated Approval pathway based on the change from baseline in anti-Factor Xa activity in healthy volunteers.

The continued approval for the indication of andexanet alfa is contingent upon post-marketing study results to demonstrate an improvement in hemostasis in patients. Additionally, there is a postmarketing commitment requirement to conduct a clinical trial randomly assigning patients to receive andexanet alfa or usual care, which is scheduled to be initiated in 2019 and to be reported in 2023, according to Lis.

Lis stated that the Generation 1 supply is limited as Portola prepares for transition to Generation 2 product. Initially, andexanet alfa will be offered to a very limited number of hospitals, through the early supply program. This is a dedicated program for about 30 to 40 hospitals that are predominantly ANNEXA-4 clinical trial sites, and a limited number of level 1 trauma and stroke centers. Limited launch starts in June and will expand later upon Generation 2 approval.

Stuart J. Connolly, MD, chairman of the ANNEXA-4 executive committee and professor in the department of medicine of the Faculty of Health Sciences at McMaster University in Hamilton, Ontario, Canada, said in the telebriefing that current evidence supports use of the drug.

“The evidence is already strong that we have a very effective drug,” he said. “The need for the [randomized controlled trial] is not going to affect how people use this drug in the present time. There’s a lot of evidence supporting its use. Patients with [intracranial hemorrhage], in particular, are at a huge risk if they continue to bleed, so physicians are going to want to use the drug.”

Lis said the company will continue to pursue indications for andexanet alfa to reverse the effects of Factor Xa inhibitors betrixaban (BevyxXa, Portola), edoxaban (Savaysa, Daiichi Sankyo) and enoxaparin, and for andexanet alfa to be used during urgent surgery.

Andexanet alfa is the second agent approved by the FDA for reversal of a direct oral anticoagulant. In 2015, idarucizumab (Praxbind, Boehringer Ingelheim) received contingent approval for reversal of the effects of dabigatran (Pradaxa, Boehringer Ingelheim). It received full approval in April.

Boehringer Ingelheim announced that idarucizumab is now stocked in 3,200 hospitals in all 50 U.S. states.

Disclosures: Connolly reports he is a consultant for or receives honoraria from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Portola and Sanofi-Aventis. Lis is an employee of Portola.

 

Stuart J. Connolly

Portola Pharmaceuticals announced the FDA approved andexanet alfa, the first antidote indicated for patients treated with rivaroxaban and apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

According to a press release from Portola, the approval of andexanet alfa (Andexxa) follows the results of the phase 3 ANNEXA studies, recently published in The New England Journal of Medicine.

As previously reported by Cardiology Today, the ANNEXA studies reported the highest rate of hemostatic efficacy for any anticoagulant reversal agent to date.

The antidote is approved for reversal of the effects of two Factor Xa inhibitors, apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) and rivaroxaban (Xarelto, Janssen), which are often prescribed to patients with nonvalvular atrial fibrillation requiring stroke protection and to patients at risk for venous thromboembolism.

“The unmet medical need and number of patients admitted to the hospital with Factor Xa-related bleeding is significant and it continues to grow,” Bill Lis, CEO of Portola, said during a telebriefing. “[There were] more than 117,000 hospital admissions in 2016 alone.”

According to a press release from Portola, Andexxa received both U.S. Orphan Drug and FDA Breakthrough Therapy designations and was approved under the FDA's Accelerated Approval pathway based on the change from baseline in anti-Factor Xa activity in healthy volunteers.

The continued approval for the indication of andexanet alfa is contingent upon post-marketing study results to demonstrate an improvement in hemostasis in patients. Additionally, there is a postmarketing commitment requirement to conduct a clinical trial randomly assigning patients to receive andexanet alfa or usual care, which is scheduled to be initiated in 2019 and to be reported in 2023, according to Lis.

Lis stated that the Generation 1 supply is limited as Portola prepares for transition to Generation 2 product. Initially, andexanet alfa will be offered to a very limited number of hospitals, through the early supply program. This is a dedicated program for about 30 to 40 hospitals that are predominantly ANNEXA-4 clinical trial sites, and a limited number of level 1 trauma and stroke centers. Limited launch starts in June and will expand later upon Generation 2 approval.

Stuart J. Connolly, MD, chairman of the ANNEXA-4 executive committee and professor in the department of medicine of the Faculty of Health Sciences at McMaster University in Hamilton, Ontario, Canada, said in the telebriefing that current evidence supports use of the drug.

“The evidence is already strong that we have a very effective drug,” he said. “The need for the [randomized controlled trial] is not going to affect how people use this drug in the present time. There’s a lot of evidence supporting its use. Patients with [intracranial hemorrhage], in particular, are at a huge risk if they continue to bleed, so physicians are going to want to use the drug.”

Lis said the company will continue to pursue indications for andexanet alfa to reverse the effects of Factor Xa inhibitors betrixaban (BevyxXa, Portola), edoxaban (Savaysa, Daiichi Sankyo) and enoxaparin, and for andexanet alfa to be used during urgent surgery.

Andexanet alfa is the second agent approved by the FDA for reversal of a direct oral anticoagulant. In 2015, idarucizumab (Praxbind, Boehringer Ingelheim) received contingent approval for reversal of the effects of dabigatran (Pradaxa, Boehringer Ingelheim). It received full approval in April.

Boehringer Ingelheim announced that idarucizumab is now stocked in 3,200 hospitals in all 50 U.S. states.

Disclosures: Connolly reports he is a consultant for or receives honoraria from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Portola and Sanofi-Aventis. Lis is an employee of Portola.