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.

It’s fi­nal­ly over: Bio­gen, Ei­sai scrap big Alzheimer’s PhI­I­Is af­ter a pre­dictable BACE cat­a­stro­phe rais­es safe­ty fears

Months after analysts and investors called on Biogen and Eisai to scrap their BACE drug for Alzheimer’s and move on in the wake of a string of late-stage failures and rising safety fears, the partners have called it quits. And they said they were dropping the drug — elenbecestat — after the independent monitoring board raised concerns about…safety.

We don’t know exactly what researchers found in this latest catastrophe, but the companies noted in their release that investigators had determined that the drug was flunking the risk/benefit analysis.

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Lisa M. DeAngelis, MSKCC

MSK picks brain can­cer ex­pert Lisa DeAn­ge­lis as its next CMO — fol­low­ing José Basel­ga’s con­tro­ver­sial ex­it

It’s official. Memorial Sloan Kettering has picked a brain cancer expert as its new physician-in-chief and CMO, replacing José Baselga, who left under a cloud after being singled out by The New York Times and ProPublica for failing to properly air his lucrative industry ties.

His replacement, who now will be in charge of MSK’s cutting-edge research work as well as the cancer care delivered by hundreds of practitioners, is Lisa M. DeAngelis. DeAngelis had been chair of the neurology department and co-founder of MSK’s brain tumor center and was moved in to the acting CMO role in the wake of Baselga’s departure.

Penn team adapts CAR-T tech, reengi­neer­ing mouse cells to treat car­diac fi­bro­sis

After establishing itself as one of the pioneer research centers in the world for CAR-T cancer therapies, creating new attack vehicles to eradicate cancer cells, a team at Penn Medicine has begun the tricky transition of using the basic technology for heart repair work.

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Tal Zaks. Moderna

The mR­NA uni­corn Mod­er­na has more ear­ly-stage hu­man da­ta it wants to show off — reach­ing new peaks in prov­ing the po­ten­tial

The whole messenger RNA field has attracted billions of dollars in public and private investor cash gambled on the prospect of getting in on the ground floor. And this morning Boston-based Moderna, one of the leaders in the field, wants to show off a few more of the cards it has to play to prove to you that they’re really in the game.

The whole hand, of course, has yet to be dealt. And there’s no telling who gets to walk with a share of the pot. But any cards on display at this point — especially after being accused of keeping its deck under lock and key — will attract plenty of attention from some very wary, and wired, observers.

“In terms of the complexity and unmet need,” says Tal Zaks, the chief medical officer, “this is peak for what we’ve accomplished.”

Moderna has two Phase I studies it wants to talk about now.

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It's not per­fect, but it's a good start: FDA pan­elists large­ly en­dorse Aim­mune's peanut al­ler­gy ther­a­py

Two days after a fairly benign review from FDA staff, an independent panel of experts largely endorsed the efficacy and safety of Aimmune’s peanut allergy therapy, laying the groundwork for approval with a risk evaluation and mitigation strategy (REMS).

Traditionally, peanut allergies are managed by avoidance, but the threat of accidental exposure cannot be nullified. Some allergists have devised a way to dose patients off-label with peanut protein derived from supermarket products to wean them off their allergies. But the idea behind Aimmune’s product was to standardize the peanut protein, and track the process of desensitization — so when accidental exposure in the real world invariably occurs, patients are less likely to experience a life-threatening allergic reaction.

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Rit­ter bombs fi­nal PhI­II for sole lac­tose in­tol­er­ance drug — shares plum­met

More than two years ago Ritter Pharmaceuticals managed to find enough silver lining in its Phase IIb/III study — after missing the top-line mark — to propel its lactose intolerance toward a confirmatory trial. But as it turned out, the enthusiasm only set the biotech and its investors up to be sorely disappointed.

This time around there’s little left to salvage. Not only did RP-G28 fail to beat placebo in reducing lactose intolerance symptoms, patients in the treatment group actually averaged a smaller improvement. On a composite score measuring symptoms like abdominal pain, cramping, bloating and gas, patients given the drug had a mean reduction of 3.159 while the placebo cohort saw a 3.420 drop on average (one-sided p-value = 0.0106).

Ear­ly snap­shot of Ad­verum's eye gene ther­a­py sparks con­cern about vi­sion loss

An early-stage update on Adverum Biotechnologies’ intravitreal gene therapy has triggered investor concern, after patients with wet age-related macular degeneration (AMD) saw their vision deteriorate, despite signs that the treatment is improving retinal anatomy.

Adverum, on Wednesday, unveiled 24-week data from the OPTIC trial of its experimental therapy, ADVM-022, in six patients who have been administered with one dose of the therapy. On average, patients in the trial had severe disease with an average of 6.2 anti-VEGF injections in the eight months prior to screening and an average annualized injection frequency of 9.3 injections.

Alex Ar­faei trades his an­a­lyst's post for a new role as biotech VC; Sanofi vet heads to Vi­for

Too often, Alex Arfaei arrived too late. 

An analyst at BMO Capital Markets, he’d meet with biotech or pharmaceutical heads for their IPO or secondary funding and his brain, trained on a biology degree and six years at Merck and Endo, would spring with questions: Why this biomarker? Why this design? Why not this endpoint? Not that he could do anything about it. These execs were coming for clinical money; their decisions had been made and finalized long ago.

Arde­lyx bags its first FDA OK for IBS, set­ting up a show­down with Al­ler­gan, Iron­wood

In the first of what it hopes will be a couple of major regulatory milestones for its new drug, Ardelyx has bagged an FDA approval to market Ibsrela (tenapanor) for irritable bowel syndrome.

The drug’s first application will be for IBS with constipation (IBS-C), inhibiting sodium-hydrogen exchanger NHE3 in the GI tract in such a way as to increase bowel movements and decrease abdominal pain. This comes on the heels of two successful Phase III trials.