Mer­ck study may sig­nal doom for a broad group of piv­otal Alzheimer’s stud­ies

The BACE the­o­ry in Alzheimer’s R&D is sim­ple. Cut off the flow of amy­loid be­ta to the brain and you can elim­i­nate what is wide­ly be­lieved — though not proven — to be a cause of the dis­ease. Do that, and you could bend the course of this dev­as­tat­ing ill­ness in mil­lions of peo­ple with mild to mod­er­ate forms of the dis­ease.

And Mer­ck $MRK just spent a for­tune to demon­strate that it may well be com­plete­ly wrong.

To be sure, Mer­ck ran a clean study for verube­ce­s­tat, the lead­ing BACE drug in the clin­ic, and dis­played the da­ta on 1,958 pa­tients for all to see to­day in the New Eng­land Jour­nal of Med­i­cine. In­ves­ti­ga­tors care­ful­ly tracked amy­loid be­ta flows in cere­brospinal cords and found that the drug did what it was in­tend­ed to do, with a dra­mat­ic re­duc­tion of the tox­ic pro­tein. 

It had no ef­fect, with pa­tients in the two dosage groups track­ing in par­al­lel de­cline on both cog­ni­tion and func­tion, the two clas­sic mea­sures for Alzheimer’s. 

The con­clu­sion they reached is that the dam­age al­ready present in the brains of pa­tients with Alzheimer’s may be too ex­ten­sive to treat with any BACE drug. And they al­so con­cede that the amy­loid the­o­ry it­self may be just flat wrong.

This sug­gests that once de­men­tia is present, dis­ease pro­gres­sion may be in­de­pen­dent of Aβ pro­duc­tion or, al­ter­na­tive­ly, that the amy­loid hy­poth­e­sis of Alzheimer’s dis­ease may not be cor­rect. Be­cause Aβ de­po­si­tion takes place years be­fore clin­i­cal symp­toms be­come ap­par­ent, it has been pro­posed that treat­ments tar­get­ing amy­loid should be im­ple­ment­ed ear­ly in the dis­ease process, be­fore the on­set of clin­i­cal symp­toms.

Soon af­ter this study failed, Mer­ck al­so threw in the tow­el on their sec­ond piv­otal tri­al, not­ing it too was a flop. Those da­ta are still be­ing eval­u­at­ed, but it un­der­scores the be­lief that all of the BACE stud­ies — in­clud­ing those at Eli Lil­ly $LLY, part­nered with As­traZeneca $AZN, or Bio­gen $BI­IB, al­lied with Ei­sai — are head­ed straight to fail­ure.

Bio­gen is al­so rolling the dice on ad­u­canum­ab, which the com­pa­ny has tout­ed as a lead­ing amy­loid be­ta ther­a­py. But with in­ves­ti­ga­tors in the field open­ly won­der­ing whether the amy­loid the­o­ry has lured a long line­up in­to a clin­i­cal dis­as­ter zone, it’s like­ly to face grow­ing skep­ti­cism that it can de­vel­op a safe, ef­fec­tive ther­a­py with just one drug.

This doesn’t by any means elim­i­nate work in the area. True, Pfiz­er re­cent­ly pulled out af­ter spend­ing hun­dreds of mil­lions of dol­lars on their pro­grams. But star­tups like De­nali be­lieve that new and bet­ter tech­nol­o­gy can give them bet­ter odds at suc­cess, while Cel­gene is jump­ing in with its own new pipeline. Oth­ers want to see if com­bi­na­tion ap­proach­es us­ing tau and amy­loid be­ta to­geth­er could work. 

Mer­ck’s sug­ges­tion about go­ing even ear­li­er in the dis­ease process has al­so prompt­ed a range of stud­ies in pre-symp­to­matic pa­tients, while the FDA has sig­naled its in­ter­est in com­ing up with bio­mark­ers to help speed new stud­ies.

Af­ter more than 200 R&D projects end­ed in dis­as­ter, though, Alzheimer’s is look­ing like an in­creas­ing­ly daunt­ing chal­lenge, with no clear path for­ward that would in­spire con­fi­dence among pa­tients with the dis­ease.

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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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).

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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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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