Investigational Factor Xa inhibitor antidote gets FDA breakthrough therapy designation
The U.S. Food and Drug Administration (FDA) has granted a breakthrough therapy designation to Portola Pharmaceuticals, Inc, for andexanet alfa (PRT4445), its investigational Factor Xa inhibitor antidote.
The FDA's breakthrough therapy designation is intended to expedite the development and review of drugs for serious or life-threatening conditions. Portola is pursuing an Accelerated Approval pathway for andexanet alfa, a first-in-class agent, and plans to initiate registration-enabling studies in 2014.
Phase 2 results to date have demonstrated that andexanet alfa's can immediately reverse the anticoagulant activity of Factor Xa inhibitors by the administration of a short intravenous bolus. This reversal can be prolonged when necessary by the addition of an extended infusion of andexanet alfa. Once administration is stopped, andexanet alfa is rapidly cleared and anticoagulant therapy can be re-initiated, which is critical for patients who have pre-existing (underlying) prothrombotic conditions.
Andexanet alfa acts as a Factor Xa decoy that targets and sequesters with high specificity both direct and indirect Factor Xa inhibitors in the blood. Once bound, the Factor Xa inhibitors are unable to bind to and inhibit native Factor Xa, thus allowing for the restoration of normal haemostatic processes.
Andexanet alfa's specific mechanism of action may also reduce the potential for serious adverse events and interactions with other commonly used drugs. No serious adverse events or antibodies to Factor Xa or Factor X have been observed in the ongoing Phase 2 studies.
"The FDA's decision to designate andexanet alfa as a breakthrough therapy reaffirms the urgent need for an antidote to Factor Xa inhibitors, and we believe it demonstrates that andexanet alfa's properties and data distinguish it from currently used agents or others in development," said William Lis, Portola's chief executive officer, in a press release.
Source: press release Portola Pharmaceuticals, November 25 2013