NEWS

Portola anticoagulant antidote Andexxa gets accelerated approval from FDA

Release time:

2018-05-24 10:16

On May 3, Portola Pharmaceutical Company announced that the US FDA has approved Andexxa [coagulation factor Xa (recombinant),inactivated-zhzo] as the first and only coagulation factor Xa inhibitor (rivaroxaban, apixaban) antidote for the reversal of anticoagulation after life-threatening or uncontrolled bleeding.

In December last year, the FDA once again said that it would postpone its approval, postponing the review date from February 3, 2018 to May 4, 2018, on the grounds that it wanted to verify the additional information it requested the company to provide. Due to production concerns, the application was initially partially rejected.

I didn't expect the good news to come so soon. This approval of Andexxa is based on FDA accelerated approval, which is based on baseline change data of anti-Xa activity in healthy volunteers, and the drug has received FDA's breakthrough therapy and orphan drug qualification. However, full approval for this indication may depend on the results of post-marketing studies, which still need to demonstrate improved hemostasis in patients.

Andexxa is developed to treat excessive blood loss in patients who have taken apixaban (the Eliquis active ingredient) or rivaroxaban (the Xarelto active ingredient).

The use of factor Xa inhibitors is rapidly increasing due to their good efficacy and safety profile compared to enoxaparin and warfarin in the prevention and treatment of thromboembolic disorders such as stroke, pulmonary embolism and venous thromboembolism (VTE). This rapid increase in use has been accompanied by an increase in bleeding-related admissions and deaths, which are major complications of anticoagulation. In 2016 alone, there were about 117000 hospitalizations for Xa inhibitor-related bleeding in the United States, and nearly 2000 deaths per month due to bleeding. This life-saving potential of Andexxa will effectively help clinicians to treat life-threatening bleeding events, which will have a significant impact on global public health. At present, Portola companies are still committed to tap more potential in the field of thrombosis and hematoma."

The approval of this Andexxa is mainly based on the trial data of ANNEXA(ANNEXA-R and ANNEXA-A) in two phase 3 clinical studies. The specific data have been published in The New England Journal of Medicine. The study evaluated the safety and efficacy of Andexxa to reverse the anticoagulant effects of Xa factor inhibitors rivaroxaban and apixaban. The results showed that Andexxa rapidly and significantly reversed anti-factor Xa activity, with a median decrease of 97% in anti-factor Xa activity (rivaroxaban) and 92% in apixaban activity compared to baseline.

As part of its review and approval, the FDA also evaluated interim data from the ongoing ANNEXA-4 single-arm open-label study of the treatment of patients with major bleeding. Data from 185 evaluable patients showed that Andexxa rapidly and significantly reversed anti-factor Xa activity upon administration and sustained reversal after 120 min. The mean decrease in activity from baseline was 90% for rivaroxaban and 93% for apixaban.

In terms of patent layout, there are as many as 9 patents related to it in the United States alone, most of which have not yet been authorized. The following are 4 examples, of which the most relevant is the US20160015793A1 filed on February 14, 2013:

       

Patent Name

Patent Number

Application Date

Modulation of factor Xa inhibitor mediated blood loss by partial and transient administration of antidote

US20160015793A1

20130214

Antidotes for factor Xa inhibitors and methods of using the same in combination with blood coagulating agents

US20140134151A1

20130430

Lyophilized formulations for factor Xa antidote

US20160237420A1

20160422

Antidotes for factor Xa inhibitors and methods of using the same

US20170233711A1

20170216