Dai­ichi Sankyo 'dis­ap­point­ed' as FDA ex­perts spurn AML drug but vote in fa­vor of rare tu­mor drug

Dai­ichi Sankyo has of­fered up the fresh­est case study of just where the line is drawn on can­cer drugs show­ing in­cre­men­tal — or even ques­tion­able — ben­e­fits, as crit­i­cal in­ter­nal re­views from the FDA trans­lat­ed in­to dif­fer­ing ad­vi­so­ry com­mit­tee opin­ions on two of its pitch­es.

By a 3-8 mar­gin, the on­col­o­gy ex­perts con­vened by the agency shot down the Japan­ese drug­mak­er’s case for its acute myeloid leukemia drug quizar­tinib, hav­ing vot­ed in fa­vor of pex­i­dar­tinib in the morn­ing ses­sion. Pex­i­dar­tinib treats be­nign tu­mors known as symp­to­matic tenosyn­ovial gi­ant cell tu­mor.

De­signed specif­i­cal­ly for FLT3-ITD–pos­i­tive AML, quizar­tinib was her­ald­ed as a sig­nif­i­cant new op­tion for re­frac­to­ry pa­tients who are count­ing their last days. Dai­ichi Sankyo bagged the ty­ro­sine ki­nase in­hibitor in a buy­out of Am­bit Bio­sciences val­ued at $410 mil­lion in 2014. Last Au­gust, the com­pa­ny scored a break­through ther­a­py des­ig­na­tion for it on the back of piv­otal da­ta that showed a 27% over­all sur­vival rate com­pared to 20% in the chemother­a­py arm.

Richard Paz­dur

But ad­comm mem­bers sided with FDA re­view­ers in wor­ry­ing that the re­sults, de­spite be­ing sta­tis­ti­cal­ly sig­nif­i­cant, had to do with im­bal­ances be­tween the drug and chemo co­horts. Com­pared to the chemo arm, the quizar­tinib group had a high­er per­cent­age of pa­tients who went on to re­ceive hematopoi­et­ic stem cell trans­plants, a low­er num­ber of non-treat­ed cas­es, and few­er in­stances of in­com­plete OS da­ta — all point­ing to­ward a po­ten­tial bias.

Richard Paz­dur, the pow­er­ful di­rec­tor of the FDA’s On­col­o­gy Cen­ter of Ex­cel­lence, chimed in at the meet­ing, say­ing he hasn’t come across a re­sult like this in 20 years.

“While we are dis­ap­point­ed by the out­come of to­day’s ODAC vote, we will work close­ly with the FDA as it com­pletes the re­view of our sub­mis­sion,” said An­toine Yver, Dai­ichi Sankyo’s glob­al head of on­col­o­gy R&D.

An­toine Yver

Reg­u­la­tors, who are not oblig­ed to fol­low the ad­comm’s ad­vice but of­ten do, will have un­til Au­gust 25 to de­cide af­ter ex­tend­ing an ear­li­er dead­line to re­view more da­ta. Dai­ichi Sankyo’s loss here could be Astel­las’ and No­var­tis’ gain as they con­tin­ue to carve out a place for Xospa­ta and Ry­dapt, re­spec­tive­ly.

It’s a sharp con­trast with pex­i­dar­tinib, which would be the first non-sur­gi­cal treat­ment for a rare but of­ten de­bil­i­tat­ing con­di­tion in­volv­ing tu­mors in joints and ten­dons.

Here the main con­cern was liv­er tox­i­c­i­ty, a con­cern that had pre­vi­ous­ly cur­tailed en­roll­ment in a Phase III. While ad­comm mem­bers ac­knowl­edged the safe­ty is­sues, the ma­jor­i­ty of them trust­ed a de­cent risk eval­u­a­tion and mit­i­ga­tion strat­e­gy, or REMS, would suf­fi­cient­ly low­er the risks.

Though the FDA al­so raised ques­tions about ef­fi­ca­cy, cit­ing a “high lev­el of miss­ing da­ta at Week 25,” 12 of the ex­perts on the pan­el had no prob­lem en­dors­ing the ben­e­fits over the risks.

“I did not see the lon­gi­tude in the da­ta around 25 weeks and this is why I took more of the con­ser­v­a­tive side,” added one of the 3 who vot­ed no. “I was wor­ried about the ef­fi­ca­cy and qual­i­ty of life da­ta be­yond 25 weeks.”

The PDU­FA date for pex­i­dar­tinib is Au­gust 3.

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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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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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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On a glob­al romp, Boehringer BD team picks up its third R&D al­liance for Ju­ly — this time fo­cused on IPF with $50M up­front

Boehringer Ingelheim’s BD team is on a global deal spree. The German pharma company just wrapped its third deal in 3 weeks, going back to Korea for its latest pipeline pact — this time focused on idiopathic pulmonary fibrosis.

They’re handing over $50 million to get their hands on BBT-877, an ATX inhibitor from Korea’s Bridge Biotherapeutics that was on display at a science conference in Dallas recently. There’s not a whole lot of data to evaluate the prospects here.

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Novotech CRO Ex­pands Chi­na Team as Biotech De­mand for Clin­i­cal Tri­als In­creas­es up to 79%

An increase in demand of up to 79% for clinical trials in China has prompted Novotech the Asia-Pacific CRO to rapidly expand the China team, appointing expert local clinical executives to their Shanghai and Hong Kong offices. The company is planning to expand their team by 30% over the next quarter.

Novotech China has seen considerable demand recently which is borne out by research from GlobalData:
A global migration of clinical research is occurring from high-income countries to low and middle-income countries with emerging economies. Over the period 2017 to 2018, for example, the number of clinical trial sites opened by biotech companies in Asia-Pacific increased by 35% compared to 8% in the rest of the world, with growth as high as 79% in China.
Novotech CEO Dr John Moller said China offers the largest population in the world, rapid economic growth, and an increasing willingness by government to invest in research and development.
Novotech’s 23 years of experience working in the region means we are the ideal CRO partner for USA biotechs wanting to tap the research expertise and opportunities that China offers.
There are over 22,000 active investigators in Greater China, with about 5,000 investigators with experience on at least 3 studies (source GlobalData).

Servi­er scoots out of an­oth­er col­lab­o­ra­tion with Macro­Gen­ics, writ­ing off their $40M

Servier is walking out on a partnership with MacroGenics $MGNX — for the second time.

After the market closed on Wednesday MacroGenics put out word that Servier is severing a deal — inked close to 7 years ago — to collaborate on the development of flotetuzumab and other Dual-Affinity Re-Targeting (DART) drugs in its pipeline.

MacroGenics CEO Scott Koenig shrugged off the departure of Servier, which paid $20 million to kick off the alliance and $20 million to option flotetuzumab — putting a heavily back-ended $1 billion-plus in additional biobuck money on the table for the anti-CD123/CD3 bispecific and its companion therapies.

Den­mark's Gen­mab hits the jack­pot with $500M+ US IPO as small­er biotechs rake in a com­bined $147M

Danish drugmaker Genmab A/S is off to the races with perhaps one of the biggest biotech public listings in decades, having reaped over $500 million on the Nasdaq, as it positions itself as a bonafide player in antibody-based cancer therapies.

The company, which has long served as J&J’s $JNJ key partner on the blockbuster multiple myeloma therapy Darzalex, has asserted it has been looking to launch its own proprietary product — one it owns at least half of — by 2025.

FDA over­rides ad­comm opin­ions a fifth of the time, study finds — but why?

For drugmakers, FDA advisory panels are often an apprehended barometer of regulators’ final decisions. While the experts’ endorsement or criticism often translate directly to final outcomes, the FDA sometimes stun observers by diverging from recommendations.

A new paper out of Milbank Quarterly put a number on that trend by analyzing 376 voting meetings and subsequent actions from 2008 through 2015, confirming the general impression that regulators tend to agree with the adcomms most of the time — with discordances in only 22% of the cases.

UP­DAT­ED: With loom­ing ‘apoc­a­lypse of drug re­sis­tance,’ Mer­ck’s com­bi­na­tion an­tibi­ot­ic scores FDA ap­proval on two fronts

Merck — one of the last large biopharmaceuticals companies in the beleaguered field of antibiotic drug development — on Wednesday said the FDA had sanctioned the approval of its combination antibacterial for the treatment of complicated urinary tract and intra-abdominal infections.

To curb the rise of drug-resistant bacteria and maintain the efficacy of the therapy, Recarbrio (and other antibacterials) — the drug must be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible gram-negative bacteria, Merck $MRK said.

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