Expert Financial Analysis and Reporting

Portola announced after the close on December 22, 2017 that the FDA will extend its review of AndexXa (andexanet alfa) by 90 days. According to the Company, it just submitted additional data requested by the agency for the ongoing ANNEXA-4 study as part of the continuing review process.  This constitutes an amendment to the submission so that the agency will need an extension to review this information. As a result, the PDUFA date has been moved from February 3, 2018 to May 4, 2018.

As a condition of approval, Portola agreed to do a phase 4 study (ANNEXA-4) in patients receiving either apixaban, rivaroxaban, edoxaban or enoxaparin and who then experienced acute major bleeding that was potentially life-threatening. The ANNEXA-A and ANNEXA-R phase 3 studies were conducted in healthy volunteers. The FDA wanted to see data involving patients experiencing major bleeds in a real life setting. The  ANNEXA-4 study began on April 10, 2015 with patients enrolling at 20 centers in the United States, 1 center in the United Kingdom, and 1 center in Canada For ethical reasons, the study was not randomized.

The study was designed to use the same dosing schedule as that used in ANNEXA-A and ANNEXA-R. All patients initially received andexanet alfa as a bolus dose over 30 minutes followed by a two-hour infusion. One of the complications of administration is that the dose chosen differs based on the anticoagulant the patient is taking and the time from the last administration. This raises concern as to whether appropriate dosing  can be accurately administered  in a busy emergency room, where the patient is likely to present and this could result in under or overdosing.

The Company has not provided further clarification. We should learn more on this in an update conference call that the Company has scheduled for January 9, 2018. The ANNEXA-4 trial  appears similar to what we are seeing with Antares. It appears to me that the FDA has grown frustrated that companies are not coming through on commitments to do studies on real world experience following approval. My best judgment is that AndexXa will be approved on May 4, 2018 whereas my previous expectation was for February 3, 2018. This news may not be well received by the investment community as Portola has frustrated investors with delay after delay. Both Bevyexxa and AndexXa received CRLs and then after Bevyexxa was approved, there was a manufacturing issue that again delayed commercial introduction from 4Q, 2017 to 1Q, 2018. And now this.

Investor frustration and uncertainty could lead to some moderate stock weakness in coming days just as a knee jerk reaction. I can understand this as I am also frustrated. However, I believe there is a very good chance for approval on May 4 and if my hypothesis is correct that the delay stems from the FDA wanting an iron clad commitment to post approval studies, we can’t blame management that much. The potential 90 day delay for AndexXa approval in the US doesn’t affect my buy recommendation on the stock.

The Company further stated that AndexXa is under review by the European Commission of the European Medicines Agency (EMA). A final decision by the European Commission on the marketing authorization application (MAA) is anticipated in the first half of 2018. There has been no change in this guidance. This adds some credence to my hypothesis that the PDUFA delay in the US is related to the FDA centric requirement for a post marketing study and not an issue with the data on safety and efficacy.