Dive Brief:
- Just a month before it was set to decide, the Food and Drug Administration has pushed back the Prescription Drug User Fee Act date for Portola Pharmaceuticals Inc.'s AndexXa by three months.
- The company seeks an initial indication as a reversal agent for the anticoagulant effects of Pfizer Inc.'s and Bristol-Myers Squibb Company's Eliquis (apixaban) and Johnson & Johnson's Xarelto (rivaroxaban) in patients with uncontrolled or life-threatening bleeding.
- Originally set for February 3, the PDUFA date is now delayed to May 4, 2018, to give the agency time to review Portola's submission of additional data from the ongoing ANNEXA-4 study and work with the company on labeling and post-marketing commitments.
Dive Insight:
Reversal agents are key for the success of the new oral anticoagulants (NOACs) market, allowing physicians to reverse the actions of blood-thinning agents quickly and effectively after trauma or before surgery. Major bleeding is a significant cause of hospital admissions and deaths in people taking Factor Xa inhibitor anticoagulants, and many patients remain on the higher-risk warfarin because of the concern about the lack of reversal options.
Boehringer Ingelheim's reversal agent Praxbind (idarucizumab) has been on the market since 2015, and is so far the only NOAC reversal agent available. Still, it only acts on the German company's NOAC Pradaxa (dabigatran).
What makes AndexXa (andexanet alfa) different, and potentially unique on the market, is that it is designed as a universal oral or injectable Factor Xa inhibitor antidote.
AndexXa's route to market, however, has been plagued with challenges.
In August 2016, the Food and Drug Administration turned down Portola's biologics license application and issued a complete response letter, citing issues related to the drug's manufacturing. The agency asked for additional information on production processes, further data to support the inclusion of Lovenox (enoxaparin) and Daiichi Sankyo Company Limited's Savaysa/Lixiana (edoxaban) in the label, and additional review of clinical amendments.
Since then, Portola snagged some additional funding through a royalty deal with HealthCare Royalty Partners (HCR) to push through clinical and regulatory activities, and launch the drug once it is approved, as well as up to $25 million from Daiichi Sankyo to expand an open label study in Germany.
The data from the Phase 3b/4 open label AndexXa study has been positive, with bleeding stopped in 79% of patients presenting with a major bleed while on a factor Xa inhibitor. The FDA accepted version two of the submission in August 2017, with a promised PDUFA data of February 2017. AndexXa is also awaiting approval in Europe, with a decision expected in the first half of 2018.