Keytru­da/epaca­do­stat com­bo crash­es in PhI­II melanoma study, rais­ing ques­tions about the fu­ture of IDO for In­cyte

A close­ly-watched Phase III study com­bin­ing Mer­ck’s PD-1 star Keytru­da with In­cyte’s IDO1 drug epaca­do­stat for metasta­t­ic melanoma has failed, cast­ing a pall over the fu­ture of this com­bi­na­tion ap­proach.

Ab­sent a sig­nif­i­cant im­prove­ment in pro­gres­sion-free sur­vival, as well as the like­ly fail­ure of the drug com­bi­na­tion to ex­tend over­all sur­vival, the in­ves­ti­ga­tors are halt­ing the study. In­cyte stuck with the top-line re­sults in their re­lease, promis­ing to roll out the full da­ta set lat­er. And they made it clear in a call with an­a­lysts this morn­ing that the ECHO-301 study fail­ure “has a neg­a­tive im­pact on the prob­a­bil­i­ty of suc­cess of the oth­er (com­bi­na­tion) stud­ies” — send­ing a shock wave through the I/O field.

In­cyte’s shares plunged 23% on the news, wip­ing out more than $3.5 bil­lion in mar­ket cap. The im­pli­ca­tions for oth­er IDO1 drugs al­so dam­aged oth­er com­pa­nies in the field, in­clud­ing NewLink $NLNK, down 44%, as well as Bris­tol-My­ers Squibb $BMY down 2.6%.

Steven Stein

Mer­ck is one of a slate of bio­phar­ma com­pa­nies to com­bine their check­points with In­cyte’s IDO drug, look­ing to im­prove pa­tients chances for liv­ing longer with can­cer. The fail­ure of this first late-stage test, af­ter stok­ing hopes for some ma­jor ad­vances, now leaves In­cyte’s drug $IN­CY in a pre­car­i­ous po­si­tion, cre­at­ing a cri­sis for CEO Hervé Hop­penot.

Epaca­do­stat was num­ber 3 on Eval­u­ate Phar­ma’s top 10 list of 2018 launch­es, with close to $2 bil­lion in pro­ject­ed peak sales es­ti­mates. And UBS an­a­lysts gave this study a 100% chance of suc­cess, not­ing the high ex­pec­ta­tions — and hype — fo­cused on this drug.

In­ves­ti­ga­tors tracked a haz­ard ra­tio of 1.00, which “leaves no doubt that in this study… the com­pound didn’t per­form,” said Steven Stein, the chief med­ical of­fi­cer, in the call. And there was no pos­i­tive glim­mer of hope seen in any sub­group analy­sis. “Giv­en those haz­ard ra­tios it is go­ing to be dif­fi­cult to dis­cern a sub­group with suf­fi­cient ef­fect.”

The fail­ure of the study al­so rais­es the chances that oth­er tri­als in the pro­gram may need to be ad­just­ed, he added, with pos­si­ble sta­tis­ti­cal and bio­mark­er mod­i­fi­ca­tions.

An­a­lysts had been en­cour­aged last sum­mer with the lat­est look at da­ta from a sin­gle-arm melanoma study, mak­ing this one of the most an­tic­i­pat­ed stud­ies of 2018. In­cyte faces a dif­fi­cult task now in re­build­ing hopes for a block­buster fu­ture as the field awaits a long string of read outs from com­bi­na­tion tri­als.

An­tic­i­pat­ing some big re­turns, a whole host of play­ers has dived in­to IDO. A re­cent study from the Can­cer Re­search In­sti­tute found that there were 18 IDOs in the pipeline. Epaca­do­stat was the most ad­vanced of them all, but there have been a num­ber of set­backs, in­clud­ing a pro­gram pur­sued by Genen­tech, which the com­pa­ny aban­doned af­ter see­ing weak re­sults. And a grow­ing line­up of fail­ures will boost fears that this is the wrong tar­get.

That woe­ful feel­ing didn’t help mat­ters at Bris­tol-My­ers, which has one of the most ad­vanced IDOs in the clin­ic af­ter In­cyte’s pro­gram. Bris­tol-My­ers paid $1.25 bil­lion to ob­tain their drug in the Flexus buy­out, which was im­pli­cat­ed in a suit In­cyte filed claim­ing that a for­mer staffer had stolen trade se­crets on their drug, hand­ing them off to Flexus. Sev­er­al an­a­lysts have out­lined rea­sons why they think that Bris­tol-My­ers has the bet­ter of the two drugs.

With the alarm bells ring­ing loud­ly all day Fri­day, NewLink re­spond­ed by putting out a re­lease as­sert­ing that its drug in­dox­i­mod had a “dif­fer­en­ti­at­ed mech­a­nism of ac­tion.” The biotech al­so said that it would do a re­view of its pro­grams in light of the set­back at In­cyte.

The failed study will help gain “un­der­stand­ing of the role of IDO1 in­hi­bi­tion in com­bi­na­tion with PD-1 an­tag­o­nists, and may in­form our broad­er epaca­do­stat clin­i­cal de­vel­op­ment pro­gram,” said Steven Stein, chief med­ical of­fi­cer, In­cyte. “We re­main ded­i­cat­ed to trans­form­ing the treat­ment of can­cer and will con­tin­ue to ex­plore how IDO1 in­hi­bi­tion and oth­er nov­el mech­a­nisms can po­ten­tial­ly im­prove out­comes for pa­tients in need.”


Im­age: Hervé Hop­penot, In­cyte CEO at an End­points News event, Jan­u­ary 2018. END­POINTS NEWS

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.

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.

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.

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 more than a week 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.