US-based Portola Pharmaceuticals has started patient enrolment in a Phase III trial designed to evaluate the safety and efficacy of its investigational recombinant Factor Xa inhibitor reversal agent 'andexanet alfa' with Bayer HealthCare and Janssen Pharmaceuticals' Factor Xa inhibitor XARELTO (rivaroxaban).
Andexanet alfa, an FDA-designated breakthrough therapy, is being developed by Portola as a potential first-in-class agent to reverse the anticoagulation activity of Factor Xa inhibitor-treated patients who are experiencing a major bleeding episode or who need emergency surgery.
Portola executive vice-president of research and development John Curnutte said the Phase III study with XARELTO is the second registration-enabling study that the company has started in 2014 under an accelerated approval pathway to achieve the goal of bringing andexanet alfa, an FDA-designated breakthrough therapy, to market as quickly as possible.
"As the number of patients taking novel oral anticoagulants has increased, so has the number of hospital visits by patients who need an antidote," Curnutte said.
The randomised, double-blind, placebo-controlled Phase III trial is designed to assess the efficacy of andexanet alfa in rapidly reversing XARELTO-induced anticoagulation.
In the trial, efficacy of andexanet alfa will be evaluated in healthy volunteers (ages 50-75 years) as showed by biomarker endpoints, including anti-Factor Xa levels, plasma free fraction of the anticoagulant and thrombin generation.
In the first part of the trial, 40 healthy volunteers will be given XARELTO 20mg once daily and then randomised in a 2:1 ratio to andexanet alfa given as an 800mg IV bolus or to placebo.
Forty healthy volunteers will be randomised in a 2:1 ratio to andexanet alfa administered as an IV bolus followed by a continuous infusion for 120 minutes or to placebo, in the second part of the study.
Portola said that participants in the trial will be followed for up to 43 days to assess safety.
The company is assessing andexanet alfa in Phase III trials with Bristol-Myers Squibb (BMS) and Pfizer's Eliquis (apixaban) and Bayer HealthCare and Janssen's XARELTO.
The trials are designed to assess the safety and efficacy of andexanet alfa in reversing Eliquis or XARELTO induced anticoagulation rapidly after an IV bolus and sustaining that effect through a continuous infusion.