FDA clears Glob­al Blood Ther­a­peu­tics to fo­cus on key bio­mark­er in piv­otal sick­le cell tri­al

Just days af­ter flesh­ing out its lat­est set of pos­i­tive da­ta from a tiny study of GBT440 for sick­le cell dis­ease, Glob­al Blood Ther­a­peu­tics $GBT says that the FDA has signed off on its piv­otal tri­al de­sign, agree­ing to stick with a key bio­mark­er for he­mo­glo­bin lev­els for the pri­ma­ry end­point, which in­ves­ti­ga­tors have al­ready suc­cess­ful­ly tried out in small­er tri­als.

Ear­li­er in Oc­to­ber, the biotech re­port­ed that among six pa­tients re­ceiv­ing treat­ment over 90 days there was a “me­di­an 1.1 g/dL (gram per deciliter) in­crease in he­mo­glo­bin con­cen­tra­tion with GBT440 treat­ment com­pared with a “0.2 g/dL de­crease with place­bo.”

That’s the same end­point GBT has now gath­ered pos­i­tive da­ta on from about 50 pa­tients, CEO Ted Love told me in a pre­view of his post-mar­ket an­nounce­ment to­day. And its used as the pri­ma­ry end­point in a late-stage study — the first Love has heard of in sick­le cell dis­ease — which will like­ly come as quite a sur­prise to many of the ob­servers in this field, he adds.

“I think many peo­ple felt that it was sim­ply a sur­ro­gate end­point,” says Love. But the biotech is shoot­ing to see the same kind of ef­fect a doc­tor would look for in or­der­ing a blood trans­fu­sion for a par­tic­u­lar­ly ane­mic pa­tient, which should trans­late in­to im­prove­ments for at least one in a slate of sec­ondary end­points that are be­ing in­clud­ed in the tri­al.

GBT’s shares shot up 18% in post-mar­ket trad­ing fol­low­ing the news break.

The most like­ly im­me­di­ate ben­e­fit should be re­flect­ed in a re­duced bur­den of fa­tigue many pa­tients are af­flict­ed with, says Love, adding that pain and fa­tigue are the two big symp­toms that pa­tients have to deal with.

The South San Fran­cis­co-based biotech will use that mark­er in a much, much larg­er study than it has ever tack­led be­fore, with about 400 pa­tients ex­pect­ed to be re­cruit­ed. The tri­al will be run in two stages, start­ing with two dos­es to iden­ti­fy the best ap­proach for stage two. The full study will test the drug over at least 24 weeks.

Fi­nal da­ta should be out in 2019, though GBT ex­ecs say that they al­so ex­pect to re­view the re­sults from the first stage of the tri­al, when it’s avail­able.

Their end­point marks a big switch from oth­er stud­ies which have fo­cused on the rate of va­so-oc­clu­sive cri­sis (VOCs), its in­ves­ti­ga­tors say, when sick­le cell shaped red blood cells oc­clude small blood ves­sels, spurring in­flam­ma­tion, in­jury and in­tense bouts of pain. Pfiz­er went with VOCs for its riv­ipansel Phase III. The pen­ny biotech Mast Ther­a­peu­tics, for ex­am­ple, re­cent­ly missed the VOC end­point, wip­ing out much of what was left of its mar­ket cap.

Pre­vi­ous SCD stud­ies have gen­er­al­ly fo­cused on VOC, de­fined as a painful cri­sis re­quir­ing hos­pi­tal or emer­gency room uti­liza­tion. But we know that pa­tients have 4-5 times more fre­quent painful crises, with or with­out uti­liza­tion. As a re­sult, the bur­den of painful crises is dra­mat­i­cal­ly un­der-re­port­ed,” said Wal­ly Smith, M.D., Flo­rence Neal Coop­er Smith Pro­fes­sor of Sick­le Cell Dis­ease Di­rec­tor, a com­pre­hen­sive sick­le cell pro­gram at Vir­ginia Com­mon­wealth Uni­ver­si­ty, in a state­ment. “By uti­liz­ing the PRO, the in­no­v­a­tive de­sign of the HOPE Study should al­low mea­sure­ment of the true bur­den of SCD painful crises and oth­er symp­toms.

Sec­ondary out­comes in­clude: The ef­fect of the drug on symp­tom ex­ac­er­ba­tions mea­sured by the com­pa­ny’s Pa­tient Re­port­ed Out­come in­stru­ment; VOCs; hos­pi­tal­iza­tions and red blood cell trans­fu­sions.

In a cor­po­rate up­date af­ter the re­lease, GBT ex­ecs added that their CMO, Eleanor Ramos, opt­ed to re­sign ef­fec­tive to­day, adding that they have enough cash to get in­to Q2 of 2018 — look for a fi­nanc­ing at an op­por­tune mo­ment — as they cov­er a study like­ly to cost about $40 mil­lion. In ad­di­tion, GBT is drop­ping a pre­clin­i­cal study for GBT18713, an oral kallikrein in­hibitor for the pre­ven­tion of hered­i­tary an­gioede­ma at­tacks, so they can fo­cus on their lead work.

Vlad Coric (Biohaven)

In an­oth­er dis­ap­point­ment for in­vestors, FDA slaps down Bio­haven’s re­vised ver­sion of an old ALS drug

Biohaven is at risk of making a habit of disappointing its investors. 

Late Friday the biotech $BHVN reported that the FDA had rejected its application for riluzole, an old drug that they had made over into a sublingual formulation that dissolves under the tongue. According to Biohaven, the FDA had a problem with the active ingredient used in a bioequivalence study back in 2017, which they got from the Canadian drugmaker Apotex.

Francesco De Rubertis

Medicxi is rolling out its biggest fund ever to back Eu­rope's top 'sci­en­tists with strange ideas'

Francesco De Rubertis built Medicxi to be the kind of biotech venture player he would have liked to have known back when he was a full time scientist.

“When I was a scientist 20 years ago I would have loved Medicxi,’ the co-founder tells me. It’s the kind of place run by and for investigators, what the Medicxi partner calls “scientists with strange ideas — a platform for the drug hunter and scientific entrepreneur. That’s what I wanted when I was a scientist.”

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Norbert Bischofberger. Kronos

Backed by some of the biggest names in biotech, Nor­bert Bischof­berg­er gets his megaround for plat­form tech out of MIT

A little over a year ago when I reported on Norbert Bischofberger’s jump from the CSO job at giant Gilead to a tiny upstart called Kronos, I noted that with his connections in biotech finance, that $18 million launch round he was starting off with could just as easily have been $100 million or more.

With his first anniversary now behind him, Bischofberger has that mega-round in the bank.

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Chas­ing Roche's ag­ing block­buster fran­chise, Am­gen/Al­ler­gan roll out Avastin, Her­ceptin knock­offs at dis­count

Let the long battle for biosimilars in the cancer space begin.

Amgen has launched its Avastin and Herceptin copycats — licensed from the predecessors of Allergan — almost two years after the FDA had stamped its approval on Mvasi (bevacizumab-awwb) and three months after the Kanjinti OK (trastuzumab-anns). While the biotech had been fielding biosimilars in Europe, this marks their first foray in the US — and the first oncology biosimilars in the country.

Seer adds ex-FDA chief Mark Mc­Clel­lan to the board; Her­cules Cap­i­tal makes it of­fi­cial for new CEO Scott Bluestein

→ On the same day it announced a $17.5 million Series C, life sciences and health data company Seer unveiled that it had lured former FDA commissioner and ex-CMS administrator Mark McClellan on to its board. “Mark’s deep understanding of the health care ecosystem and visionary insights on policy reform will be crucial in informing our thinking as we work to bring our liquid biopsy and life sciences products to market,” said Seer chief and founder Omid Farokhzad in a statement.

Daniel O'Day

No­var­tis hands off 3 pre­clin­i­cal pro­grams to the an­tivi­ral R&D mas­ters at Gilead

Gilead CEO Daniel O’Day’s new task hunting up a CSO for the company isn’t stopping the industry’s dominant antiviral player from doing pipeline deals.

The big biotech today snapped up 3 preclinical antiviral programs from pharma giant Novartis, with drugs promising to treat human rhinovirus, influenza and herpes viruses. We don’t know what the upfront is, but the back end has $291 million in milestones baked in.

Vas Narasimhan, AP Images

On a hot streak, No­var­tis ex­ecs run the odds on their two most im­por­tant PhI­II read­outs. Which is 0.01% more like­ly to suc­ceed?

Novartis CEO Vas Narasimhan is living in the sweet spot right now.

The numbers are running a bit better than expected, the pipeline — which he assembled as development chief — is performing and the stock popped more than 4% on Thursday as the executive team ran through their assessment of Q2 performance.

Year-to-date the stock is up 28%, so the investors will be beaming. Anyone looking for chinks in their armor — and there are plenty giving it a shot — right now focus on payer acceptance of their $2.1 million gene therapy Zolgensma, where it’s early days. And CAR-T continues to underperform, but Novartis doesn’t appear to be suffering from it.

So what could go wrong?

Actually, not much. But Tim Anderson at Wolfe pressed Narasimhan and his development chief John Tsai to pick which of two looming Phase III readouts with blockbuster implication had the better odds of success.

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Af­ter a decade, Vi­iV CSO John Pot­tage says it's time to step down — and he's hand­ing the job to long­time col­league Kim Smith

ViiV Healthcare has always been something unique in the global drug industry.

Owned by GlaxoSmithKline and Pfizer — with GSK in the lead as majority owner — it was created 10 years ago in a time of deep turmoil for the field as something independent of the pharma giants, but with access to lots of infrastructural support on demand. While R&D at the mother ship inside GSK was souring, a razor-focused ViiV provided a rare bright spot, challenging Gilead on a lucrative front in delivering new combinations that require fewer therapies with a more easily tolerated regimen.

They kept a massive number of people alive who would otherwise have been facing a death sentence. And they made money.

And throughout, John Pottage has been the chief scientific and chief medical officer.

Until now.

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H1 analy­sis: The high-stakes ta­ble in the biotech deals casi­no is pay­ing out some record-set­ting win­nings

For years the big trend among dealmakers at the major players has been centered on ratcheting down upfront payments in favor of bigger milestones. Better known as biobucks for some. But with the top 15 companies competing for the kind of “transformative” pacts that can whip up some excitement on Wall Street, with some big biotechs like Regeneron now weighing in as well, cash is king at the high stakes table.

We asked Chris Dokomajilar, the head of DealForma, to crunch the numbers for us, looking over the top 20 deals for the past decade and breaking it all down into the top alliances already created in 2019. Gilead has clearly tipped the scales in terms of the coin of the bio-realm, with its record-setting $5 billion upfront to tie up to Galapagos’ entire pipeline.

Dokomajilar notes:

We’re going to need a ‘three comma club’ for the deals with over $1 billion in total upfront cash and equity. The $100 million-plus club is getting crowded at 164 deals in the last decade with new deals being added towards the top of the chart. 2019 already has 14 deals with at least $100 million in upfront cash and equity for a total year-to-date of over $9 billion. That beats last year’s $8 billion and sets a record.

Add upfronts and equity payments and you get $11.5 billion for the year, just shy of last year’s record-setting $11.8 billion.

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