Photo by Piotr Bodzek
The US Food and Drug Administration (FDA) has granted orphan designation to andexanet alfa for reversing the anticoagulant effect of factor Xa inhibitors in patients experiencing a serious, uncontrolled bleeding event and those who require urgent or emergent surgery.
At present, there is no approved antidote for these patients.
Andexanet alfa is the only compound being studied as a reversal agent for factor Xa inhibitors that directly and specifically corrects anti-factor Xa activity.
The drug 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 inhibitors are unable to bind to and inhibit native factor Xa, thus allowing for the restoration of normal hemostatic processes.
Andexanet alfa has the potential to address several clinical scenarios where a factor Xa antidote is needed by allowing for flexible and controlled reversal. This can be short-acting, through the administration of an intravenous (IV) bolus, or longer-acting with the addition of an extended infusion.
The FDA previously granted andexanet alfa breakthrough therapy designation, which is intended to expedite the development and review of a drug candidate intended to treat a serious or life-threatening condition.
“Orphan drug designation for andexanet alfa recognizes its potential to address a significant unmet medical need and to advance the field by helping patients who currently have no treatment options,” said Bill Lis, chief executive officer of Portola Pharmaceuticals, the company developing andexanet alfa.
The FDA’s orphan drug designation program provides orphan status to drugs and biologics that are intended for the treatment, diagnosis, or prevention of rare diseases/disorders that currently affect fewer than 200,000 people in the US.
Orphan designation qualifies a company for certain benefits, including an accelerated approval process, 7 years of market exclusivity following the drug’s approval, tax credits on US clinical trials, eligibility for orphan drug grants, and a waiver of certain administrative fees.
Clinical development of andexanet alfa
Researchers are currently evaluating andexanet alfa in 2 randomized, placebo-controlled, phase 3 trials—ANNEXA-A and ANNEXA-R.
They previously reported promising results from the first part of the ANNEXA-A study, a test of andexanet alfa’s ability to reverse the effects of apixaban in healthy subjects when the antidote was given as a single IV bolus.
Researchers also reported favorable results from the first part of the ANNEXA-R study, in which they evaluated andexanet alfa’s ability to reverse the effects of rivaroxaban in healthy subjects when the antidote was given as a single IV bolus.
The second parts of the ANNEXA-A and ANNEXA-R studies are ongoing. The researchers are evaluating the use of andexanet alfa given as a bolus and a continuous infusion.
ANNEXA-4, a phase 4, single-arm, confirmatory study is also ongoing. Researchers are evaluating the drug in patients receiving apixaban, rivaroxaban, edoxaban, or enoxaparin who present with an acute major bleed.
