Portola gets CRL for anticoagulant antidote AndexXa tied to manufacturing

FDA sign

Portola believed its manufacturing design was in good shape after an April meeting with FDA inspectors who checked out the facility where it will manufacture AndexXa, its breakthrough anticoagulant reversal agent. But Portola execs acknowledged today those good feelings were misplaced and that the FDA has issued a complete response letter for the drug focused primarily on manufacturing questions.

Portola ($PTLA) Wednesday reported the CRL to investors, saying the FDA requested more information about manufacturing, but also additional data for inclusion of the anticoagulants edoxaban and enoxaparin in the label. The agency also told the company that it needs more time to review the clinical amendments to Portola’s postmarketing commitments that it has recently submitted.

The delay also affects companies like Bristol-Myers Squibb ($BMY) and Pfizer ($PFE), which market the anticoagulant Eliquis for which AndexXa would serve as a bleeding antidote.

In a call today with analysts, CEO Bill Lis said Portola was “surprised” by the requests for more information on manufacturing. He said there were a handful of observations during the inspection and that they did not appear critical. He said the fact that Portola received very little feedback after the inspection led it to believe the FDA was satisfied with its responses to those observations.

“There seems to be a disconnect in our interpretation,” said Lis, who explained Portola will know more after a meeting with the FDA to go over the CRL.

John Curnutte, Portola's executive VP of research and development, told analysts that there was not a fundamental concern about Portola's ability to make the drug. However, due to the nature of a breakthrough review like AndexXa received, the review goes so quickly that the drugmaker and FDA know as far as validation, some matters will be answered during the post-approval period. He said now it is clear the FDA wants more of those matters resolved before approval.

“There are some things we thought we would be able to do on the other side of the river but which they want done on this side,” Curnutte said.

Portola joins a growing list of companies that this year have had approvals of their drugs delayed over manufacturing matters. Valeant Pharmaceuticals and Ocular Therapeutix both got CRLs last month for their eye drugs. In May, AstraZeneca ($AZN) said it had received a CRL for its investigational treatment for hyperkalemia, a drug candidate that was the target of AstraZeneca’s $2.7 billion buyout of ZS Pharma. This was also tied to manufacturing problems. And before that, Miami-based OPKO ($OPK) received a CRL because of issues the FDA had with the manufacturing plant in Florida where its drugs are being manufactured by Catalent ($CTLT).

- here’s the Portola announcement

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