Portola Pharmaceuticals ($PTLA) has snapped in the last piece to a Phase III program puzzle for its "breakthrough" anti-anticoagulant, painting a clear path to an accelerated regulatory submission later in the year.
In the second part of its Phase III study of andexanet alfa, Portola investigators say that their antidote to the blockbuster Factor Xa inhibitor Eliquis achieved all primary and secondary endpoints with "high statistical significance," confirming the same results seen in the first part of the trial. The biotech presented top-line results only, adding that the data will be presented at some future conference.
Their antidote--which earned the FDA's breakthrough therapy designation--is a molecule that is designed to latch onto Factor Xa inhibitors like Eliquis, disarming their activity when needed to prevent excessive bleeding. Portola got a big bounce last fall when it announced that the first leg of the Phase III was a success. The absence of any surprises this morning kept the stock gain to a couple of percentage points.
"Andexanet alfa distinguishes itself as the only Factor Xa inhibitor antidote in development shown to bind to oral FXa inhibitors and have a significant impact on three critical biomarkers: anti-Factor Xa activity, thrombin generation and free fraction of the anticoagulant," says Dr. John Curnutte, executive vice president of research and development for Portola. "Both the FDA and European Medicines Agency have agreed that the reduction of anti-Factor Xa activity is an acceptable primary endpoint for Accelerated Approval (Expedited or Conditional Approval in the EU) with supporting secondary endpoints, including normalization of thrombin generation and sequestration of the anticoagulant. Given the highly statistically significant efficacy results we have seen in Phase II and Phase III studies across oral and injectable Factor Xa inhibitors, we believe andexanet alfa has the potential to be a first-in-class antidote for patients taking a Factor Xa anticoagulant who suffer a major bleeding episode or require emergency surgery."
Phase III was made up of two small study groups. In the first part, 33 healthy volunteers were given apixaban (Eliquis) 5 mg twice daily for four days and then randomized in a 3:1 ratio to andexanet alfa administered as a 400-mg IV bolus (n=24) or to placebo (n=9). Today's top-line results for the second part of the study covered 31 healthy volunteers who were given apixaban 5 mg twice daily for four days and then randomized in a 3:1 ratio to andexanet alfa administered as a 400-mg IV bolus followed by a continuous infusion of 4 mg/min for 120 minutes (n=23) or to placebo (n=8).
South San Francisco-based Portola still has programs underway with Johnson & Johnson's ($JNJ) Xarelto--the first part of the Phase III also was counted a full success, with the data indicating the same kind of rapid response seen with Eliquis--and Daiichi Sankyo's experimental edoxaban, looking to gain an edge over competitors in the pipeline. The biotech also has its own anticoagulant, betrixaban, in Phase III as well.
Bernstein's Geoffrey Porges has counted himself among the analysts confident that Portola is on the right track with the Phase III program. He's far less happy with some manufacturing snafus that appear to be setting the stage for limited supplies postapproval. In a recent note to investors he related that manufacturing problems will likely drive up costs to $20,000 per "bleed"--at least initially.
- here's the release