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%.

UP­DAT­ED: Mer­ck pulls Keytru­da in SCLC af­ter ac­cel­er­at­ed nod. Is the FDA get­ting tough on drug­mak­ers that don't hit their marks?

In what could be an early shot in the battle against drugmakers that whiff on confirmatory studies to support accelerated approvals, the FDA ordered Bristol Myers Squibb late last year to give up Opdivo’s approval in SCLC. Now, Merck is next on the firing line — are we seeing the FDA buckling down on post-marketing offenders?

Merck has withdrawn its marketing approval for PD-(L)1 inhibitor Keytruda in metastatic small cell lung cancer as part of what it describes as an “industry-wide evaluation” by the FDA of drugs that do not meet the post-marketing checkpoints on which their accelerated nods were based, the company said Monday.

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Pascal Soriot, AstraZeneca CEO (AP Images)

Pas­cal So­ri­ot cash­es in As­traZeneca’s chips on Mod­er­na for $1.2B cash in­jec­tion

While still working to prove its own Covid-19 vaccine, AstraZeneca has reportedly capitalized on the success of another.

The company has sold off its 7.7% stake in Moderna and turned it into $1.2 billion in cash, according to the Times, beefing up the reserves just as Pascal Soriot is wrapping up his $39 billion acquisition of Alexion and its rare disease pipeline.

AstraZeneca’s stock sale follows a similar move by Merck in December. But like its pharma brethren, the British giant is keeping its R&D collaborations with Moderna.

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Bob Nelsen (Photo by Michael Kovac/Getty Images)

With stars aligned and cash in re­serve, Bob Nelsen's Re­silience plans a makeover at 2 new fa­cil­i­ty ad­di­tions to its drug man­u­fac­tur­ing up­start

Bob Nelsen’s new, state-of-the-art drug manufacturing initiative is taking shape.

Just 3 months after gathering $800 million of launch money, a dream team board and a plan to shake up a field where he found too many bottlenecks and inefficiencies for the era of Covid-19, Resilience has snapped up a pair of facilities now in line for a retooling.

The company has acquired a 310,000-square-foot plant in Boston from Sanofi along with a 136,000-square-foot plant in Ontario to add to a network which CEO Rahul Singhvi says is just getting started on building his company’s operations up. The Sanofi deal comes with a contract to continue manufacturing one of its drugs.

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Af­ter bail­ing on Covid-19 vac­cines, Mer­ck will team up with J&J to pro­duce its shot as part of un­usu­al Big Phar­ma pact

Merck took a big gamble when it opted to jump into the Covid-19 vaccine race late, and made an equally momentous decision to back out in late January. Now, looking to chip in on the effort, Merck reportedly agreed to team up with one of the companies that has already crossed the finish line.

President Joe Biden on Tuesday is expected to announce a partnership between drugmakers Merck and Johnson & Johnson to jointly produce J&J’s recombinant protein Covid-19 vaccine that received the FDA’s emergency use authorization Saturday, the Washington Post reported.

Ab­b­Vie tees up a biotech buy­out af­ter siz­ing up their Parkin­son's drug spun out of Ke­van Shokat's lab

AbbVie has teed up a small but intriguing biotech buyout after looking over the preclinical work it’s been doing in Parkinson’s disease.

The company is called Mitokinin, a Bay Area biotech spun out of the lab of UCSF’s Kevan Shokat, whose scientific explorations have formed the academic basis of a slew of startups in the biotech hub. One of Shokat’s PhD students in the lab, Nicholas Hertz, co-founded Mitokinin using their lab work on PINK1 suggesting that amping up its activity could play an important role in regulating the mitochondrial dysfunction contributing to Parkinson’s disease pathogenesis and progression.

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Paul Sekhri

The next big biotech su­per­star? Paul Sekhri has some thoughts on that

It occasionally occurs to Paul Sekhri that if they pull this off, his company will be on the front page of the New York Times and a lead story in just about every major news outlet on the planet. He tries not to dwell on it, though.

“I just want to be laser-focused on getting to that point,” Sekhri says, before acknowledging, “Yes, it absolutely crossed my mind.”

Sekhri, a longtime biopharma executive with tenures at Sanofi and Novartis, is now entering year three as CEO of eGenesis, the biotech that George Church protégé Luhan Yang founded to genetically alter pigs so that they can be used for organ transplants. He led them through one megaround and has just closed another, raising $125 million from 17 different investors to push the first-ever (humanized) pig to human transplants into the clinic.

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Fi­bro­Gen shares skid low­er as a sur­prise ad­comm rais­es risks on roxa OK

FibroGen will likely have to delay its US rollout for roxadustat once again.

In an unexpected move, the FDA is convening its Cardiovascular and Renal Drugs Advisory Committee to review the NDA in an advisory committee meeting. The date is yet to be confirmed.

Just a few weeks ago, SVB Leerink analyst Geoffrey Porges predicted that the roxa approval could come ahead of the PDUFA date on March 20 — effusive despite already being let down once by the FDA’s extension of its review back in December. AstraZeneca, which is partnered with FibroGen on the chronic kidney disease-related anemia drug, disclosed regulators had requested further clarifying analyses of clinical data.

In­tro­duc­ing End­pointsF­DA+, our new pre­mi­um week­ly reg­u­la­to­ry news re­port led by Zachary Bren­nan

CRLs. 483s. CBER, CDER and RWE. For biopharma professionals, these acronyms command attention because of the fundamental role FDA plays in drug development. Now Endpoints is doubling down on regulatory coverage, and launching a weekly report focusing on developments out of White Oak, with analysis and insight into what it all means.

Coverage will be led by our new senior editor, Zachary Brennan. He joins Endpoints from POLITICO, where he covered pharma. Prior to that he was the managing editor for Regulatory Focus, a news publication from the Regulatory Affairs Professionals Society.

UP­DAT­ED: Feds clear the road for J&J to start de­liv­er­ing mil­lions of dos­es of their Covid-19 vac­cine — but frets linger about run­ner-up sta­tus

All the pieces needed to trigger a third wave of Covid-19 vaccine supply to start washing over the US fell neatly into place over the weekend.

After providing for a brief mime of regulatory judiciousness, the FDA stamped their emergency approval on J&J’s Covid-19 vaccine Saturday, adding to the Biden administration’s plan aimed at ending the pandemic in the near term — at least in the US. The CDC came through on Sunday with its stamp of approval and J&J is reportedly expected to start delivering vaccine sometime in the next few days.

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