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%.

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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FDA de­lays de­ci­sion on No­var­tis’ po­ten­tial block­buster MS drug, wip­ing away pri­or­i­ty re­view

So much for a speedy review.

In February, Novartis announced that an application for their much-touted multiple sclerosis drug ofatumumab had been accepted and, with the drug company cashing in on one of their priority review vouchers, the agency was due for a decision by June.

But with June less than 48 hours old, Novartis announced the agency has extended their review, pushing back the timeline for approval or rejection to September. The Swiss pharma filed the application in December, meaning their new schedule will be nearly in line with the standard 10-month window period had they not used the priority voucher.

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Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

Joseph Kim, Inovio CEO (Andrew Harnik, AP Images)

Caught in a stand­off with its con­tract man­u­fac­tur­er over Covid-19 vac­cine, In­ovio files suit in an at­tempt to break free while ri­vals race ahead

Inovio was one of the first vaccine developers to snag attention for a jab that their execs said promised to end the Covid-19 pandemic. Using their own unique DNA tech, CEO Joseph Kim said it took just 3 hours to work it out.

But while rivals are racing to the finish line with ambitious plans to make vast quantities of their vaccines with billions of dollars of deals, Inovio is still stuck at the starting line on manufacturing.

UP­DAT­ED: Es­ti­mat­ing a US price tag of $5K per course, remde­sivir is set to make bil­lions for Gilead, says key an­a­lyst

Data on remdesivir — the first drug shown to benefit Covid-19 patients in a randomized, controlled trial setting — may be murky, but its maker Gilead could reap billions from the sales of the failed Ebola therapy, according to an estimate by a prominent Wall Street analyst. However, the forecast, which is based on a $5,000-per-course US price tag, triggered the ire of one top drug price expert.

Covid-19 roundup: Mod­er­na read­ies to en­ter PhI­II in Ju­ly, As­traZeneca not far be­hind; EU ready to ne­go­ti­ate vac­cine ac­cess with $2.7B fund

Moderna may soon add another first to the Covid-19 vaccine race.

In March, the mRNA biotech was the first company to put a Covid-19 vaccine into humans. Next month, they may become the first company to put their vaccine into the large, late-stage trials that are needed to prove whether the vaccine is effective.

In an interview with JAMA editor Howard Bauchner, NIAID chief Anthony Fauci said that a 30,000-person, Phase III trial for Moderna’s vaccine could start in July. The news comes a week after Moderna began a Phase II study that will enroll several hundred people.

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José Basel­ga finds promise in new class of RNA-mod­i­fy­ing can­cer tar­gets, lock­ing in 3 pre­clin­i­cal pro­grams with $55M

Having dived early into some of the RNA breakthroughs of the last decades — betting on Moderna’s mRNA tech and teaming up with Silence on the siRNA front — AstraZeneca is jumping into a new arena: going after proteins that modify RNA.

Their partner of choice is Accent Therapeutics, which is receiving $55 million in upfront payment to steer a selected preclinical program through to the end of Phase I. After AstraZeneca takes over, the Lexington, MA-based startup has the option to co-develop and co-commercialize in the US — and collect up to $1.1 billion in milestones in the long run. The deal also covers two other potential drug candidates.

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