User login
Photo courtesy of Pfizer
and Bristol-Myers Squibb
The US Food and Drug Administration (FDA) has issued a complete response letter regarding the biologics license application for andexanet alfa (AndexXa™).
Andexanet alfa is being developed as a reversal agent for the factor Xa inhibitors apixaban, rivaroxaban, edoxaban, and enoxaparin.
The agent is intended to be used when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.
In the complete response letter, the FDA requested that Portola Pharmaceuticals Inc., the company developing andexanet alfa, provide additional information related to manufacturing.
Portola said it could not provide many details on this request but stressed that the FDA did not question the company’s ability to manufacture the drug.
The FDA also asked Portola for additional data to support the inclusion of edoxaban and enoxaparin on andexanet alfa’s label.
The completed phase 3 studies of andexanet alfa were designed to assess the drug’s ability to reverse the effects of apixaban and rivaroxaban—but not edoxaban or enoxaparin—in healthy volunteers. Andexanet alfa’s effects on edoxaban and enoxaparin have been investigated in phase 2 studies, however.
Portola had assumed these studies would be sufficient because, overall, the research suggests andexanet alfa has broad activity against factor Xa inhibitors, according to Bill Lis, chief executive officer of Portola.
Lis also noted that the primary use of andexanet alfa, once approved, would be in patients receiving rivaroxaban or apixaban because fewer patients take edoxaban and enoxaparin.
The final issue the FDA mentioned in the complete response letter was the need to finalize its review of the clinical amendments to Portola’s post-marketing commitments.
“Because AndexXa addresses an urgent unmet medical need, we and the FDA are committed to resolving the outstanding questions and determining appropriate next steps,” Lis said.
“Portola’s goal is to define the most expedient path to approval so we can meet the needs of these patients who have no alternative. We plan to meet with the FDA as soon as possible.”
About andexanet alfa
Andexanet alfa is a modified human factor Xa molecule that acts as a decoy to target and sequester both oral and injectable factor Xa inhibitors in the blood. Once bound, the factor Xa inhibitors are unable to bind to and inhibit native factor Xa, thus potentially allowing for the restoration of normal hemostatic processes.
The FDA granted andexanet alfa orphan drug designation last year and breakthrough therapy designation in 2013.
Portola’s biologics license application for andexanet alfa was based on data from a pair of phase 3 studies of healthy volunteers—ANNEXA-A and ANNEXA-R.
In the ANNEXA-R trial, andexanet alfa successfully reversed the anticoagulant activity of rivaroxaban. In the ANNEXA-A trial, andexanet alfa reversed the anticoagulant activity of apixaban.
Results from these studies were published in NEJM last year.
The biologics license application also included limited adjudicated efficacy and safety data from initial patients enrolled in the ongoing ANNEXA-4 study.
In this phase 3b/4 study, researchers are evaluating andexanet alfa in patients receiving apixaban, rivaroxaban, edoxaban, or enoxaparin who present with an acute major bleed. 
Photo courtesy of Pfizer
and Bristol-Myers Squibb
The US Food and Drug Administration (FDA) has issued a complete response letter regarding the biologics license application for andexanet alfa (AndexXa™).
Andexanet alfa is being developed as a reversal agent for the factor Xa inhibitors apixaban, rivaroxaban, edoxaban, and enoxaparin.
The agent is intended to be used when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.
In the complete response letter, the FDA requested that Portola Pharmaceuticals Inc., the company developing andexanet alfa, provide additional information related to manufacturing.
Portola said it could not provide many details on this request but stressed that the FDA did not question the company’s ability to manufacture the drug.
The FDA also asked Portola for additional data to support the inclusion of edoxaban and enoxaparin on andexanet alfa’s label.
The completed phase 3 studies of andexanet alfa were designed to assess the drug’s ability to reverse the effects of apixaban and rivaroxaban—but not edoxaban or enoxaparin—in healthy volunteers. Andexanet alfa’s effects on edoxaban and enoxaparin have been investigated in phase 2 studies, however.
Portola had assumed these studies would be sufficient because, overall, the research suggests andexanet alfa has broad activity against factor Xa inhibitors, according to Bill Lis, chief executive officer of Portola.
Lis also noted that the primary use of andexanet alfa, once approved, would be in patients receiving rivaroxaban or apixaban because fewer patients take edoxaban and enoxaparin.
The final issue the FDA mentioned in the complete response letter was the need to finalize its review of the clinical amendments to Portola’s post-marketing commitments.
“Because AndexXa addresses an urgent unmet medical need, we and the FDA are committed to resolving the outstanding questions and determining appropriate next steps,” Lis said.
“Portola’s goal is to define the most expedient path to approval so we can meet the needs of these patients who have no alternative. We plan to meet with the FDA as soon as possible.”
About andexanet alfa
Andexanet alfa is a modified human factor Xa molecule that acts as a decoy to target and sequester both oral and injectable factor Xa inhibitors in the blood. Once bound, the factor Xa inhibitors are unable to bind to and inhibit native factor Xa, thus potentially allowing for the restoration of normal hemostatic processes.
The FDA granted andexanet alfa orphan drug designation last year and breakthrough therapy designation in 2013.
Portola’s biologics license application for andexanet alfa was based on data from a pair of phase 3 studies of healthy volunteers—ANNEXA-A and ANNEXA-R.
In the ANNEXA-R trial, andexanet alfa successfully reversed the anticoagulant activity of rivaroxaban. In the ANNEXA-A trial, andexanet alfa reversed the anticoagulant activity of apixaban.
Results from these studies were published in NEJM last year.
The biologics license application also included limited adjudicated efficacy and safety data from initial patients enrolled in the ongoing ANNEXA-4 study.
In this phase 3b/4 study, researchers are evaluating andexanet alfa in patients receiving apixaban, rivaroxaban, edoxaban, or enoxaparin who present with an acute major bleed.
Photo courtesy of Pfizer
and Bristol-Myers Squibb
The US Food and Drug Administration (FDA) has issued a complete response letter regarding the biologics license application for andexanet alfa (AndexXa™).
Andexanet alfa is being developed as a reversal agent for the factor Xa inhibitors apixaban, rivaroxaban, edoxaban, and enoxaparin.
The agent is intended to be used when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.
In the complete response letter, the FDA requested that Portola Pharmaceuticals Inc., the company developing andexanet alfa, provide additional information related to manufacturing.
Portola said it could not provide many details on this request but stressed that the FDA did not question the company’s ability to manufacture the drug.
The FDA also asked Portola for additional data to support the inclusion of edoxaban and enoxaparin on andexanet alfa’s label.
The completed phase 3 studies of andexanet alfa were designed to assess the drug’s ability to reverse the effects of apixaban and rivaroxaban—but not edoxaban or enoxaparin—in healthy volunteers. Andexanet alfa’s effects on edoxaban and enoxaparin have been investigated in phase 2 studies, however.
Portola had assumed these studies would be sufficient because, overall, the research suggests andexanet alfa has broad activity against factor Xa inhibitors, according to Bill Lis, chief executive officer of Portola.
Lis also noted that the primary use of andexanet alfa, once approved, would be in patients receiving rivaroxaban or apixaban because fewer patients take edoxaban and enoxaparin.
The final issue the FDA mentioned in the complete response letter was the need to finalize its review of the clinical amendments to Portola’s post-marketing commitments.
“Because AndexXa addresses an urgent unmet medical need, we and the FDA are committed to resolving the outstanding questions and determining appropriate next steps,” Lis said.
“Portola’s goal is to define the most expedient path to approval so we can meet the needs of these patients who have no alternative. We plan to meet with the FDA as soon as possible.”
About andexanet alfa
Andexanet alfa is a modified human factor Xa molecule that acts as a decoy to target and sequester both oral and injectable factor Xa inhibitors in the blood. Once bound, the factor Xa inhibitors are unable to bind to and inhibit native factor Xa, thus potentially allowing for the restoration of normal hemostatic processes.
The FDA granted andexanet alfa orphan drug designation last year and breakthrough therapy designation in 2013.
Portola’s biologics license application for andexanet alfa was based on data from a pair of phase 3 studies of healthy volunteers—ANNEXA-A and ANNEXA-R.
In the ANNEXA-R trial, andexanet alfa successfully reversed the anticoagulant activity of rivaroxaban. In the ANNEXA-A trial, andexanet alfa reversed the anticoagulant activity of apixaban.
Results from these studies were published in NEJM last year.
The biologics license application also included limited adjudicated efficacy and safety data from initial patients enrolled in the ongoing ANNEXA-4 study.
In this phase 3b/4 study, researchers are evaluating andexanet alfa in patients receiving apixaban, rivaroxaban, edoxaban, or enoxaparin who present with an acute major bleed.