Portola Pharmaceuticals’ efforts to secure approval for its novel oral anticoagulant (NOAC) and reversal agent in Europe have hit another snag.
The US company revealed at the end of last year that the EMA’s Committee for Medicinal Products for Human Use (CHMP) had asked for additional information on its marketing applications for betrixaban, its oral, once-daily Factor Xa inhibitor, as well as antidote drug andexanet alfa.
Now, it seems that while applications for andexanet alfa may be getting back on track, it will likely be delayed until the fourth quarter according to Portola CEO Bill Lis. Moreover, the CHMP still have concerns about betrixaban that will continue to delay approval, even though it has already been approved by the US FDA as Bevyxxa.
“The CHMP communicated a negative trend vote for betrixaban for the prevention of venous thromboembolism (VTE) in adult patients hospitalised for an acute medical illness with risk factors for VTE,” said Portola in a statement. That means it is “unlikely that the CHMP will adopt a positive opinion on the Company’s MAA at the formal CHMP decision vote scheduled for March 2018”, it added.
It seems that the CHMP may ask for another betrixaban trial. While it seems to agree with the positive efficacy findings in Portola’s APEX study “uncertainties remain regarding a positive benefit risk, which is not supported by a second confirmatory study”, according to Lis, who said that verdict is “particularly disappointing” and means that the company will now focus its efforts on the US market.
The committee is also concerned that Portola’s agent is in an acute medically ill population, a patient group in which the other Factor Xa inhibitors – Pfizer/Bristol-Myers Squibb’s Eliquis (apixaban), Bayer/Johnson & Johnson’s Xarelto (rivaroxaban) and Daiichi Sankyo’s Lixiana/Savaysa (edoxaban) – have thus far not been approved.
The Californian company is however hopeful of a positive verdict on andexanet alfa this year, which would be a boost to the company as the drug has already been turned down by the FDA in 2016 but is due to deliver verdict on a re-filed application in May.
In the meantime, Boehringer Ingelheim’s rival NOAC Pradaxa (dabigatran) – which works by inhibiting thrombin – remains the only new anticoagulant on the market with a reversal agent available. In October 2015 the FDA granted accelerated approval to Boehringer’s Praxbind (idarucizumab) reversal agent, and the availability of the antidote seems to have had a positive impact on sales in 2016.