Por­to­la slammed by a sur­pris­ing FDA re­jec­tion for its an­ti-an­ti­co­ag­u­lant

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.”

Bill Lis, Por­to­la CEO

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%.

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

President Trump walks past HHS secretary Alex Azar (Getty Images)

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CDC’s Robert Redfield, NIAID’s Anthony Fauci, Admiral Brett Giroir at HHS, and FDA’s Stephen Hahn prepare to testify at a House hearing on June 23 (Getty)

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David Berry (Flagship)

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