Up­dat­ed: Cel­gene, Agios win a land­mark FDA OK for new AML drug Id­hi­fa

David Schenkein, Agios CEO

Cel­gene and Agios didn’t have to wait un­til the PDU­FA date at the end of Au­gust to get a speedy FDA de­ci­sion on enasi­denib (AG-221), their new ther­a­py for acute myeloid leukemia. The FDA cut to the chase and ap­proved it to­day.

Cel­gene $CELG re­worked its deal with Agios $AGIO last year, but kept its hands on its rights to AG-221 in pa­tients with ad­vanced hema­to­log­ic ma­lig­nan­cies with an IDH2 mu­ta­tion. In turn, Agios stayed ra­zor fo­cused on grab­bing the ear­li­est pos­si­ble ap­proval, hus­tling Phase I/II da­ta straight to reg­u­la­tors for an ac­cel­er­at­ed re­view.

The drug will now be sold as Id­hi­fa, con­cen­trat­ing on about 9% to 13% of the AML mar­ket.

“The use of Id­hi­fa was as­so­ci­at­ed with a com­plete re­mis­sion in some pa­tients and a re­duc­tion in the need for both red cell and platelet trans­fu­sions,” not­ed the FDA’s Richard Paz­dur in herald­ing the OK to­day. The drug will be used with the Re­al­Time IDH2 As­say, which is used to de­tect spe­cif­ic mu­ta­tions in the IDH2 gene in pa­tients with AML.

It won’t come cheap. From Cel­gene:

The ap­proval of ID­HI­FA rep­re­sents a new, tar­get­ed ther­a­py for a sub­type of AML with an ex­treme­ly rare ge­net­ic mu­ta­tion. The 8-19% of AML pa­tients that have an IDH2 mu­ta­tion rep­re­sent about 1,200 to 1,500 in­di­vid­u­als in the U.S. These pa­tients are liv­ing with dis­ease that has a poor prog­no­sis and no stan­dard of care and no oth­er cur­rent­ly ap­proved op­tions un­til to­day. Pair­ing this ther­a­py with an ap­proved com­pan­ion di­ag­nos­tic al­so sig­nif­i­cant­ly im­proves iden­ti­fi­ca­tion of el­i­gi­ble pa­tients who could ben­e­fit from this new­ly ap­proved treat­ment.

The month­ly whole­sale ac­qui­si­tion cost of ID­HI­FA is $24,872. In the piv­otal study, the me­di­an time on ther­a­py for pa­tients was 4.3 months

Cel­gene first al­lied it­self with Agios back in 2010, part­ner­ing on its work in can­cer me­tab­o­lism. That deal led Cel­gene to grab world­wide rights to AG-221 in 2014. Cel­gene hand­ed back rights to AG-120, an IDH1 in­hibitor, but al­so an­ted up an­oth­er $200 mil­lion to grab op­tions on a slate of ex­per­i­men­tal drugs in the biotech’s pipeline.

The re­la­tion­ship paid off nice­ly for Cel­gene. The jour­ney from first-in-hu­man test­ing to a reg­u­la­to­ry fil­ing took just three years, an in­cred­i­bly fast speed in R&D. And Agios plans to do that again with oth­er drugs in its pipeline. Leerink’s says it’s a big step for both com­pa­nies, which will be fol­lowed close­ly dur­ing the mar­ket launch.

This is the first drug to emerge from Cel­gene’s col­lab­o­ra­tion with Agios, and from Agios’ re­search plat­form in can­cer me­tab­o­lism, and al­so the first drug to be ap­proved from Cel­gene’s net­worked re­search arrange­ments. It pro­vides im­por­tant val­i­da­tion for both plat­form and strat­e­gy, and in­vestors will close­ly mon­i­tor the drug’s com­mer­cial per­for­mance to as­sess how well these ad­vances trans­late in­to com­mer­cial suc­cess. Cel­gene is the pri­ma­ry com­mer­cial­iz­ing par­ty in the US, al­though Agios has opt­ed in to co-com­mer­cial­ize the prod­uct in the US. Cel­gene has sug­gest­ed that they will add ap­prox­i­mate­ly 30 head­count to sup­port the prod­uct’s com­mer­cial­iza­tion on the US. Cel­gene es­ti­mates that there is a tar­get­ed pa­tient pop­u­la­tion of 1,200-1,500 pa­tients in the US and ex­pects the du­ra­tion of treat­ment to ap­prox­i­mate the 4 months ob­served in the phase I/II tri­al.

Leerink’s Michael Schmidt al­so took a step back and sized up the im­pli­ca­tions for the biotech, now that it owns the IDH1 ther­a­py. It all adds up to a siz­able op­por­tu­ni­ty, he notes:

In our view, FDA-ap­proval of Id­hi­fa al­so re­duces reg­u­la­to­ry risk for ivosi­denib in AML, the lat­ter be­ing pro­pri­etary to AGIO and hence rep­re­sent­ing a more sig­nif­i­cant val­ue dri­ver for the com­pa­ny. AGIO’s IDH1 & 2 in­hibitors ad­dress a ~$270M and ~$370M glob­al mar­ket op­por­tu­ni­ty in re­lapsed/re­frac­to­ry AML, re­spec­tive­ly, based on our up­dat­ed es­ti­mates; po­ten­tial front-line use in com­bi­na­tion with ap­proved or in­ves­ti­ga­tion­al agents re­flects a sig­nif­i­cant­ly larg­er $1Bn+ com­mer­cial op­por­tu­ni­ty based on our re­cent due dili­gence should on­go­ing and planned front-line clin­i­cal tri­als suc­ceed.

CEO David Schenkein is fond of re­call­ing Agios start­ed out with lit­tle more than a blank sheet of pa­per. Since then, the pages have been filled with high-pro­file part­ner­ships, an IPO for its po­ten­tial cut­ting-edge work and now its first new drug ap­proval. It’s a wa­ter­shed mo­ment for this biotech.

 

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:

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,400+ biopharma pros reading Endpoints daily — and it's free.

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.

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.

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.

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.

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.

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.