Portola has finally overcome FDA concerns to win approval of its coagulation factor Xa, a bleeding antidote for some of the new generation blood thinners like Xarelto and Eliquis. Portola will launch Andexxa next month, although initial supplies will be limited by a manufacturing changeover required by the FDA.

The FDA approval for Andexaa came Thursday, 19 months after the agency’s rejection of the breakthrough designated orphan drug. It is the first and only antidote for life-threatening or uncontrolled bleeding in patients taking blood thinners made with rivaroxaban and apixaban.

"Today’s approval represents a significant step forward in patient care and one that the medical community has been eagerly anticipating," Stuart J. Connolly, M.D., ANNEXA-4 executive committee chairman and professor in the Department of Medicine at McMaster University in Hamilton, Ontario, said in the announcement.

In fact, the market is substantial. In 2016 there were more than 117,000 hospital admissions for uncontrolled bleeding for which Andexxa could have been used, Portola CEO Bill Lis told analysts during a call Friday. The wholesale price of the drug will be $27,500, which means there is potential for blockbuster sales to ring up quickly.

There is no question Andrexxa is eagerly anticipated by a foursome of major pharma players whose popular blood thinners have no antidote for excessive bleeding. Andexxa will serve as reversal agent for Johnson & Johnson’s Xarelto, Bristol-Myers Squibb and Pfizer’s Eliquis, and Daiichi Sankyo’s Savaysa. The availability of Andexxa will help in their competition with Boehringer Ingelheim, whose blood thinner Pradaxa, for which a bleeding reversal agent was approved in 2015, and reduce the risk of litigation that has mounted against the companies as a result of bleeding events.  

Pfizer and Bristol-Myers were anxious enough about seeing the bleeding antidote reach the market that when Portola was hit with a complete response letter in August 2016 over manufacturing questions, they kicked in $50 million in unsecured loans to help Portola get to the finish line with the treatment. They have a marketing agreement with Portola for Andrexxa.

But while demand is anticipated to be high for Andrexxa, supply is expected to be limited until early next year. That is when the South San Francisco, California, biotech hopes to win FDA approval for a new manufacturing process which it has been validating. The company and its CDMO Lonza had to revise Andexxa's manufacturing processes after the FDA raised concerns in the CRL about their original processes. 

Lis feels confident in that process being approved, and the FDA drug approval suggests the FDA does too.

"We are doing really well on technical standpoint, yield standpoint and the ability to take it from API to product," Portola CEO Bill Lis said in a call with analysts Friday after the drug’s approval. He said the company is also building up significant data on bioequivalence between the two processes.

But because a timetable suggests the FDA may not do a preapproval plant inspection and sign off on the new process until early next year, Portola will be limited to clinical supply on hand for its launch in June.

Lis said the drug will initially be provided to only 40 or 50 hospitals and other providers, most of which served as clinical trial sites. Assuming the company gains approval for the second generation manufacturing process, then it will be able to serve about 1,000 providers, the CEO told analysts.

Additionally, the FDA made its approval contingent upon Portola conducting a post-marketing study to demonstrate an improvement in hemostasis in patients which will require a trial that the company said would begin next year and conclude in 2023.

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