Mer­ck can’t prove its Alzheimer’s drug works, yet, but it did just ex­plain why it’s spend­ing a for­tune on PhI­II

In­ves­ti­ga­tors for Mer­ck $MRK have very care­ful­ly out­lined all the ear­ly-stage hu­man and an­i­mal da­ta they can muster for their Alzheimer’s drug verube­ce­s­tat. Now in an am­bi­tious Phase III due to read out in mid-2017, tests proved that the BACE drug can suc­cess­ful­ly tar­get one of the key bio­mark­ers for the dis­ease.

They just don’t have any con­vinc­ing da­ta to show whether it will ac­tu­al­ly make a dif­fer­ence in pa­tients’ cog­ni­tive abil­i­ties, or im­prove their abil­i­ty to func­tion in their dai­ly lives.

In many ways, Mer­ck’s case echoes all the up­beat da­ta we’ve heard about Alzheimer’s drugs in re­cent years, and al­so helps ex­plain why this field has been so frus­trat­ing.

First, the da­ta. The key take­away from the ar­ti­cle in Sci­ence Trans­la­tion­al Med­i­cine is that Mer­ck’s drug sig­nif­i­cant­ly re­duced lev­els of amy­loid be­ta in the flu­id sur­round­ing the brain among the ac­tu­al pa­tients tak­ing the drug. Dos­ing was short, with on­ly 32 pa­tients get­ting the drug dai­ly for a week.

That’s not near­ly enough time to de­tect any re­duc­tion in these tox­ic clus­ters by way of a brain scan. And it’s far short of any kind of ev­i­dence that the ther­a­py can ac­tu­al­ly have an im­pact on a dis­ease that dam­ages the brain, per­haps ir­rev­o­ca­bly.

But it does ex­plain why Mer­ck and oth­ers are spend­ing a for­tune on late-stage stud­ies on these BACE drugs.

The mech­a­nism of ac­tion for this drug lies up­stream of amy­loid be­ta. It’s de­signed to in­ter­fere with the pro­duc­tion of amy­loid be­ta, cut­ting the sup­ply of a pro­tein that has be­come one of the chief cul­prits in the dis­ease. Ratch­et down the flow of amy­loid be­ta, the the­o­ry goes, and you can pre­vent the cog­ni­tive and phys­i­cal erup­tions that even­tu­al­ly wipe out a per­son’s mem­o­ry and re­quires care­ful su­per­vi­sion.

The prob­lem with these stud­ies is that com­pa­nies like Mer­ck — and this in­cludes com­pa­nies like Eli Lil­ly, Bio­gen, J&J and many oth­ers — of­ten jump from a Phase I bio­mark­er study in­to broad Phase III stud­ies, look­ing for ev­i­dence that they can bend a re­morse­less dis­ease curve.

Mer­ck al­so in­clud­ed da­ta from its stud­ies in­volv­ing an­i­mals and healthy sub­jects. But aside from pro­vid­ing im­por­tant in­sights on safe­ty, such re­sults rarely mean much of any­thing when it comes to pre­dict­ing ef­fi­ca­cy. But big com­pa­nies are will­ing to over­look big is­sues as they hus­tle in­to late-stage Alzheimer’s tri­als.

Lil­ly was so com­mit­ted to solanezum­ab — which al­so tar­gets amy­loid be­ta — that it mount­ed a new Phase III pro­gram af­ter the last one failed. It al­so re­cent­ly rel­e­gat­ed one key mea­sure on func­tion to a sec­ondary end­point, flag­ging its lack of con­fi­dence on that score.

And most in­ves­ti­ga­tors in the field are mov­ing up­stream in the dis­ease pathol­o­gy, hop­ing to check the dis­ease be­fore it caus­es se­ri­ous dam­age.

De­spite bil­lions spent on new tri­als over the past decade, though, the field has been af­flict­ed by one set­back af­ter the next. Now Mer­ck will take the most ad­vanced study on BACE and help set the stage for a new field in which ri­vals are hus­tling along com­pet­ing ther­a­pies, hop­ing to cash in on one of the biggest un­met med­ical needs in the busi­ness.

Lil­ly will be first up with new Phase III da­ta on solanezum­ab in a mat­ter of weeks. Mer­ck will fol­low in Ju­ly. Some­time over the next year, we’ll be able to un­der­stand much bet­ter just what role amy­loid be­ta plays in Alzheimer’s. And if any­one scores pay dirt da­ta, the pay­off will po­ten­tial­ly be worth bil­lions a year from a new drug fran­chise. Losers will be rel­e­gat­ed to a grow­ing ceme­tery of failed pro­grams.

Novotech CEO Dr. John Moller

Novotech CRO Award­ed Frost & Sul­li­van Best Biotech CRO Asia-Pa­cif­ic 2019

Known in the in­dus­try as the Asia-Pa­cif­ic CRO, Novotech is now lead CRO ser­vices provider for the grow­ing num­ber of in­ter­na­tion­al biotechs se­lect­ing the re­gion for their stud­ies.

Re­flect­ing this Asia-Pa­cif­ic growth, Novotech staff num­bers are up 20% since De­cem­ber 2018 to 600 in-house clin­i­cal re­search peo­ple across a full range of ser­vices, across the re­gion.

Novotech’s ca­pa­bil­i­ties have been rec­og­nized by an­a­lysts like Frost & Sul­li­van, most re­cent­ly with the pres­ti­gious Asia-Pa­cif­ic CRO Biotech of the year award for best prac­tices in clin­i­cal re­search for biotechs for the fifth year. See oth­er awards here.

Bet­ter than Am­bi­en? Min­er­va soars on PhI­Ib up­date on sel­torex­ant for in­som­nia

A month af­ter roil­ing in­vestors with what skep­tics dis­missed as cher­ry pick­ing of its de­pres­sion da­ta, Min­er­va is back with a clean slate of da­ta from its Phase IIb in­som­nia tri­al.

In a de­tailed up­date, the Waltham, MA-based biotech said sel­torex­ant (MIN-202) hit both the pri­ma­ry and sev­er­al sec­ondary end­points, ef­fec­tive­ly im­prov­ing sleep in­duc­tion and pro­long­ing sleep du­ra­tion. In­ves­ti­ga­tors made a point to note that the ef­fects were con­sis­tent across the adult and el­der­ly pop­u­la­tions, with the lat­ter more prone to the sleep dis­or­der.

Gene ther­a­py biotech sees its stock rock­et high­er on promis­ing re­sults for rare cas­es of but­ter­fly dis­ease

Shares of Krys­tal Biotech took off this morn­ing $KRYS af­ter the lit­tle biotech re­port­ed promis­ing re­sults from its gene ther­a­py to treat a rare skin dis­ease called epi­der­mol­y­sis bul­losa.

Fo­cus­ing on an up­date with 4 new pa­tients, re­searchers spot­light­ed the suc­cess of KB103 in clos­ing some stub­born wounds. Krys­tal says that of 4 re­cur­ring and 2 chron­ic skin wounds treat­ed with the gene ther­a­py, the KB103 group saw the clo­sure of 5. The 6th — a chron­ic wound, de­fined as a wound that had re­mained open for more than 12 weeks — was par­tial­ly closed. That brings the to­tal so far to 8 treat­ed wounds, with 7 clo­sures.

Alex­ion wins pri­or­i­ty re­view for Ul­tomiris' aHUS in­di­ca­tion; FDA ex­pands ap­proval of Ver­tex's Symdeko

→ Alex­ion $ALXN has scored a speedy re­view for Ul­tomiris for pa­tients with atyp­i­cal he­molyt­ic ure­mic syn­drome (aHUS) af­ter post­ing pos­i­tive da­ta from a piv­otal study in Jan­u­ary. The drug is the rare dis­ease com­pa­ny’s shot at pro­tect­ing its block­buster blood dis­or­der fran­chise that is cur­rent­ly cen­tered around its flag­ship drug, Soliris, which is a com­ple­ment in­hibitor typ­i­cal­ly ad­min­is­tered every two weeks. Ul­tomiris has a sim­i­lar mech­a­nism of ac­tion but re­quires less-fre­quent dos­ing — every eight weeks. The de­ci­sion date has been set to Oc­to­ber 19. Late last year, Ul­tomiris se­cured ap­proval for noc­tur­nal he­mo­glo­bin­uria (PNH) pa­tients.

Ab­b­Vie gets a green light to re­sume re­cruit­ing pa­tients for one myelo­ma study — but Ven­clex­ta re­mains un­der a cloud

Three months af­ter reg­u­la­tors at the FDA forced Ab­b­Vie to halt en­rolling pa­tients in its tri­als of a com­bi­na­tion us­ing Ven­clex­ta (vene­to­clax) to treat drug-re­sis­tant cas­es of mul­ti­ple myelo­ma, the agency has green-light­ed the re­sump­tion of one of those stud­ies, while keep­ing the rest on the side­lines.

The CANO­VA (M13-494) study can now get back in busi­ness re­cruit­ing pa­tients to test the drug for a pop­u­la­tion that shares a par­tic­u­lar ge­net­ic bio­mark­er. To get that per­mis­sion, Ab­b­Vie — which is part­nered with Roche on this pro­gram — was forced to re­vise the pro­to­col, mak­ing un­spec­i­fied changes in­volv­ing risk mit­i­ga­tion mea­sures, pro­to­col-spec­i­fied guide­lines and an up­dat­ed fu­til­i­ty cri­te­ria.

UP­DAT­ED: In sur­prise switch, Bris­tol-My­ers is sell­ing off block­buster Ote­zla, promis­ing to com­plete Cel­gene ac­qui­si­tion — just lat­er

Apart from revealing its checkpoint inhibitor Opdivo blew a big liver cancer study on Monday, Bristol-Myers Squibb said its plans to swallow Celgene will require the sale of blockbuster psoriasis treatment Otezla to keep the Federal Trade Commission (FTC) at bay.

The announcement — which has potentially delayed the completion of the takeover to early 2020 — irked investors, triggering the New York-based drugmaker’s shares to tumble Monday morning in premarket trading.

Celgene’s Otezla, approved in 2014 for psoriasis and psoriatic arthritis, is a rising star. It generated global sales of $1.6 billion last year, up from the nearly $1.3 billion in 2017. Apart from the partial overlap of Bristol-Myers injectable Orencia, the company’s rival oral TYK2 psoriasis drug is in late-stage development, after the firm posted encouraging mid-stage data on the drug, BMS-986165, last fall. With Monday’s decision, it appears Bristol-Myers is favoring its experimental drug, and discounting Otezla’s future.

The move blindsided some analysts. Credit Suisse’s Vamil Divan noted just days ago:

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Bris­tol-My­ers star Op­di­vo fails sur­vival test in a matchup with Nex­avar aimed at shak­ing up the big HCC mar­ket

Bris­tol-My­ers Squibb has suf­fered an­oth­er painful set­back in its years-long quest to ex­pand the reach of Op­di­vo. The phar­ma gi­ant this morn­ing not­ed that their Check­mate-459 study com­par­ing Op­di­vo with Bay­er’s Nex­avar in front­line cas­es of he­pa­to­cel­lu­lar car­ci­no­ma — the most com­mon form of liv­er can­cer — failed to hit the pri­ma­ry end­point on over­all sur­vival.

This was a sig­nif­i­cant mile­stone in Bris­tol-My­ers’ tal­ly of PD-1 cat­a­lysts this year. Nex­avar (so­rafenib) has been the stan­dard of care in front­line HCC for the past decade, though Op­di­vo has been mak­ing head­way in sec­ond-line HCC cas­es, where it’s go­ing toe-to-toe with Bay­er’s Sti­var­ga (re­go­rafenib) af­ter re­cent ap­provals shook up the mar­ket.

Fol­low­ing news of job cuts in Eu­ro­pean R&D ops, Sanofi con­firms it’s of­fer­ing US work­ers an 'ear­ly ex­it'

Ear­li­er in the week we learned that Sanofi was bring­ing out the bud­get ax to trim 466 R&D jobs in Eu­rope, re­tool­ing its ap­proach to car­dio as re­search chief John Reed beefed up their work in can­cer and gene ther­a­pies. And we’re end­ing the week with news that the phar­ma gi­ant has al­so been qui­et­ly re­duc­ing staff in the US, tar­get­ing hun­dreds of jobs as the com­pa­ny push­es vol­un­tary buy­outs with a fo­cus on R&D sup­port ser­vices.

Why would the FDA ap­prove an­oth­er con­tro­ver­sial drug to spur a woman’s li­bido with these da­ta? And why no ex­pert pan­el re­view?

AMAG Pharmaceuticals’ newly approved drug for spurring women’s sexual desire may never make much money, but it’s a big hit at sparking media attention.

The therapy — Vyleesi (bremelanotide) — got the green light from regulators on Friday evening, swiftly lighting up a range of stories around the world, from The New York Times to The Guardian. Several headlines inevitably referred to it as the “female Viagra,” invoking Pfizer’s old erectile dysfunction blockbuster.

But the two drugs have little in common.

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