Portola Pharmaceuticals waited until late Wednesday to spread the word that the FDA has rejected its marketing application for its anti-anticoagulant andexanet alfa, a surprising setback for a company that had been confidently assuring analysts of its likely success.
Their antidote–which earned the FDA’s breakthrough therapy designation–is a molecule that is designed to quickly disarm Factor Xa anticoagulants like Eliquis and Xarelto, blocking their activity when needed to prevent excessive bleeding. Portola $PTLA got a big bounce in late 2014 when it announced that the first leg of the Phase III was a success. And they followed up in the spring of 2015 with a confirmatory leg of the Phase III program that reassured analysts that the South San Francisco-based company was on the right track.
But it wasn’t. And the rejection comes soon after Portola was forced to defend its development effort for the anticoagulant betrixaban, which failed a pivotal trial last spring.
Geoffrey Porges had counted himself among the group expecting an approval. But he had been rankled by manufacturing snafus that were likely to drive up the cost of the treatment.
The company’s statement said that the agency is now looking for more information on manufacturing with “additional data to support inclusion of edoxaban (Savaysa) and enoxaparin (Lovenox) in the label, and indicated it needs to finalize its review of the clinical amendments to Portola’s post-marketing commitments that recently were submitted.”
In a conference call with analysts today, company CEO Bill Lis said that “we were most surprised” by the CMC questions, which factored in as the predominant part of the CRL. “We were led to believe we were in very good shape on this front.”
R&D chief John T. Curnutte added that the company was tripped up by the speed of the breakthrough drug process, with the review going too fast for Portola to “dot every ‘i’ and cross every ‘t’” on bookkeeping and validation. The company had thought that any outstanding issues could be handled post-approval, but regulators weren’t in a forgiving mood.
As for the rest of the data the FDA was looking for, Lis said that the main focus at the company had been Xarelto (rivaroxaban) and Eliquis (apixaban), and regulators wanted more healthy volunteer data on the other drugs. Lis also told analysts that it was possible that Portola would be able to resubmit “by the end of the year,” but he was uncertain exactly how long the delay would be and would remain in the dark until he had a chance to discuss it with the FDA.
Portola published late-stage data last fall that showed the drug could take effect in a matter of minutes, essentially working as a decoy to attract the attention of the anti-coagulants away from their intended target.
The rejection will raise further questions about the company’s credibility and command of R&D after the late-stage failure of betrixaban. The drug fell short of success, but Portola’s Lis insisted that the data were good enough for an approval. Now the CEO’s thoughts on what is and is not ready for the FDA will have to be taken with a grain of salt — not the position the company wanted to be in at this stage.
Not everyone may have been surprised by the FDA’s action. Portola’s shares plunged 10% through regular trading on Wednesday, then dropped another 13% in after-market trading, before it issued its statement. In pre-market trading Thursday shares were down about 20%.
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