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.

Fangliang Zhang, AP Images

UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

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.

President Donald Trump (left) and Moncef Slaoui, head of Operation Warp Speed (Alex Brandon, AP Images)

UP­DAT­ED: White House names fi­nal­ists for Op­er­a­tion Warp Speed — with 5 ex­pect­ed names and one no­table omis­sion

A month after word first broke of the Trump Administration’s plan to rapidly accelerate the development and production of a Covid-19 vaccine, the White House has selected the five vaccine candidates they consider most likely to succeed, The New York Times reported.

Most of the names in the plan, known as Operation Warp Speed, will come as little surprise to those who have watched the last four months of vaccine developments: Moderna, which was the first vaccine to reach humans and is now the furthest along of any US effort; J&J, which has not gone into trials but received around $500 million in funding from BARDA earlier this year; the joint AstraZeneca-Oxford venture which was granted $1.2 billion from BARDA two weeks ago; Pfizer, which has been working with the mRNA biotech BioNTech; and Merck, which just entered the race and expects to put their two vaccine candidates into humans later this year.

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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Mer­ck wins a third FDA nod for an­tibi­ot­ic; Mereo tack­les TIG­IT with $70M raise in hand

Merck — one of the last big pharma bastions in the beleaguered field of antibiotic drug development — on Friday said the FDA had signed off on using its combination drug, Recarbrio, with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. The drug could come handy for use in hospitalized patients who are afflicted with Covid-19, who carry a higher risk of contracting secondary bacterial infections. Once SARS-CoV-2, the virus behind Covid-19, infects the airways, it engages the immune system, giving other pathogens free rein to pillage and plunder as they please — the issue is particularly pertinent in patients on ventilators, which in any case are breeding grounds for infectious bacteria.

RA Cap­i­tal, Hill­house join $310M rush to back Ever­est's climb to com­mer­cial heights in Chi­na

Money has never been an issue for Everest Medicines. With an essentially open tab from their founders at C-Bridge Capital, the biotech has gone two and a half years racking up drug after drug, bringing in top exec after top exec, and issuing clinical update after update.

But now other investors want in — and they’re betting big.

Everest is closing its Series C at $310 million. The first $50 million comes from the Jiashan National Economic and Technological Development Zone; the remaining C-2 tranche was led by Janchor Partners, with RA Capital Management and Hillhouse Capital as co-leaders. Decheng Capital, GT Fund, Janus Henderson Investors, Rock Springs Capital, Octagon Investments all joined.