Trad­ing places with Bris­tol-My­ers, Mer­ck hit with an­oth­er late-stage set­back on check­point star Keytru­da

Close to a year af­ter Mer­ck $MRK won an ac­cel­er­at­ed FDA OK to use its PD-1 check­point star Keytru­da for treat­ing sec­ond-line cas­es head and neck squa­mous cell car­ci­no­ma in com­bi­na­tion with plat­inum-con­tain­ing chemo, the phar­ma gi­ant an­nounced that its big Phase III study for that in­di­ca­tion failed.

The piv­otal KEYNOTE-040 tri­al failed to meet the pri­ma­ry end­point on over­all sur­vival in com­par­ing the block­buster check­point against stan­dard ther­a­pies, the phar­ma gi­ant re­port­ed. But the cur­rent ap­proval stands nev­er­the­less, Mer­ck said in a state­ment.

“The com­pa­ny not­ed that the FDA re­mains com­fort­able with the drug’s cur­rent ac­cel­er­at­ed ap­proval in this in­di­ca­tion de­spite the tri­al re­sults,” ob­served Leerink’s Sea­mus Fer­nan­dez. “Im­por­tant­ly, Keytru­da ap­pears to have an­oth­er shot on goal for full ap­proval in H&N can­cer, as the Keynote-048 study in first-line pa­tients could, if pos­i­tive, serve as the con­fir­ma­to­ry tri­al.”

Roger Perl­mut­ter, Mer­ck

Mer­ck didn’t pro­vide a lot of de­tails, but this is the lat­est in a se­ries of set­backs in the field that have be­gun to show the out­er lim­its of ef­fi­ca­cy for a new class of can­cer med that has trans­formed on­col­o­gy ther­a­py in the past two years. But right now, those out­er lim­its of ef­fi­ca­cy run along a blur­ry line, with no clear ex­pla­na­tions for what is caus­ing these sud­den break­downs.

Mer­ck re­cent­ly was forced to put a slate of 3 Keytru­da tri­als for mul­ti­ple myelo­ma on hold af­ter in­ves­ti­ga­tors spot­ted a high­er rate of death in the check­point arm. Two of those stud­ies used com­bi­na­tions with Cel­gene drugs, Po­m­a­lyst and its big drug Revlim­id.

Mer­ck has ini­ti­at­ed hun­dreds of stud­ies, in­clud­ing some 300 com­bi­na­tion stud­ies, as it races to cap­i­tal­ize on its new lead in the field af­ter Bris­tol-My­ers Squibb ran in­to se­ri­ous is­sues with a failed study for lung can­cer. It’s clear that af­ter see­ing some re­mark­able im­prove­ments for a sig­nif­i­cant mi­nor­i­ty of check­point pa­tients, these ther­a­pies have their lim­its. Roche has al­so had its own prob­lems with the fail­ure of a Phase III con­fir­ma­to­ry study us­ing Tecen­triq.

Bris­tol-My­ers’ Op­di­vo, mean­while, post­ed pos­i­tive Phase III da­ta on squa­mous cell car­ci­no­ma of the head and neck back in late 2016, with a me­di­an OS of 7.5 months for Op­di­vo com­pared to 5.1 months for in­ves­ti­ga­tor’s choice.

What to make of that?

“Up un­til yes­ter­day,” not­ed Ever­core ISI’s Umer Raf­fat, “I would have told you that there are at least 2 dif­fer­ent in­di­ca­tions where MRK worked and oth­ers failed … and per­haps MRK is just ex­e­cut­ing these tri­als much bet­ter.  How­ev­er, as of to­day, there ap­pears to be no con­sis­ten­cy in the in­con­sis­ten­cy.  Now MRK failed where BMY worked.”

“We are en­cour­aged by the pos­i­tive im­pact that KEYTRU­DA has had on many can­cer pa­tients, in­clud­ing those with pre­vi­ous­ly treat­ed re­cur­rent or metasta­t­ic head and neck can­cer, and we re­main con­fi­dent that KEYTRU­DA is an im­por­tant ther­a­py for this dif­fi­cult-to-treat can­cer,” said Roger Dansey, late-stage on­col­o­gy de­vel­op­ment leader, Mer­ck Re­search Lab­o­ra­to­ries. “We look for­ward to shar­ing the com­pre­hen­sive da­ta analy­sis from KEYNOTE-040 with the sci­en­tif­ic com­mu­ni­ty at an up­com­ing med­ical meet­ing.”

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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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.

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.

Suf­fer­ing No­var­tis part­ner Cona­tus is pack­ing it in on NASH af­ter a se­ries of un­for­tu­nate tri­al events

The NASH par­ty is over at No­var­tis-backed Cona­tus. And this time they’re turn­ing off the lights.

More than 2 years af­ter No­var­tis sur­prised the biotech in­vest­ment com­mu­ni­ty with its $50 mil­lion up­front and promise of R&D sup­port to part­ner with the lit­tle biotech on NASH — ig­nit­ing a light­ning strike for the share price — Cona­tus $CNAT is back with the lat­est bit­ter tale to tell about em­ri­c­as­an, which once in­spired con­fi­dence at the phar­ma gi­ant.

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.

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.

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.

Dean Hum. Nasdaq via YouTube

Gen­fit goes to Chi­na with a deal worth up to $228M for NASH drug

Fresh off the high of its Nas­daq IPO de­but, and the low of com­par­isons to Cymabay — whose NASH drug re­cent­ly stum­bled — Gen­fit on Mon­day un­veiled an up to $228 mil­lion deal with transpa­cif­ic biotech Terns Phar­ma­ceu­ti­cals to de­vel­op its flag­ship ex­per­i­men­tal liv­er drug — elafi­bra­nor — in Greater Chi­na.

The deal comes weeks af­ter Gen­fit $GN­FT is­sued a fiery de­fense of its dual PPAR ag­o­nist elafi­bra­nor, when com­peti­tor Cymabay’s PPARδ ag­o­nist, se­ladel­par, fiz­zled in a snap­shot of da­ta from an on­go­ing mid-stage tri­al. The main goal at the end of 12 weeks was for se­ladel­par to in­duce a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in liv­er fat con­tent, but da­ta showed that pa­tients on the place­bo ac­tu­al­ly per­formed bet­ter.