EMA im­pos­es for­mal lim­it on Xel­janz pre­scrip­tion as reg­u­la­tors con­tin­ue to re­view safe­ty con­cerns

Three months af­ter Pfiz­er flagged blood clot is­sues and a high­er rate of deaths for rheuma­toid arthri­tis pa­tients tak­ing the 10 mg dose of Xel­janz (to­fac­i­tinib) in a post-mar­ket­ing safe­ty study, the EMA has hand­ed down of­fi­cial re­stric­tions in its use.

The agency’s safe­ty com­mit­tee — phar­ma­covig­i­lance risk as­sess­ment com­mit­tee, or PRAC — is still in the process of re­view­ing the ev­i­dence, but it is alarmed enough to ban pre­scrip­tion of the 10 mg twice dai­ly reg­i­men in any pa­tients with a high risk of blood clots in the lungs. Those who have heart fail­ure, can­cer, a his­to­ry or pre­dis­po­si­tion to blood clots are on the list, as are pa­tients tak­ing hor­mone-based ther­a­pies or prepar­ing/re­cov­er­ing from ma­jor surgery.

And reg­u­la­tors made sure to be crys­tal clear about the im­pli­ca­tions:

The new ad­vice means that, since 10 mg is the on­ly rec­om­mend­ed start­ing dose for ul­cer­a­tive col­i­tis, pa­tients with this con­di­tion who are at high risk of blood clots must not be start­ed on Xel­janz. Pa­tients at high risk cur­rent­ly tak­ing this dose for any con­di­tion must be switched to al­ter­na­tive treat­ments.

The for­mal — though tem­po­rary — re­stric­tions fol­low an ear­li­er warn­ing, which di­rect­ed health­care pro­fes­sion­als to mon­i­tor pa­tients for signs and symp­toms of blood clots in the lungs. Doc­tors were al­so ad­vised to stick to the rec­om­mend­ed 5 mg dose when treat­ing rheuma­toid arthri­tis.

In Feb­ru­ary, Pfiz­er yanked the 10 mg dose from the on­go­ing A3921133 study in rheuma­toid arthri­tis, switch­ing pa­tients to the 5 mg dose af­ter doc­u­ment­ing “a sta­tis­ti­cal­ly and clin­i­cal­ly im­por­tant dif­fer­ence in the oc­cur­rence of pul­monary em­bolism” as well as an im­bal­ance in the rate of death. In ad­di­tion to the 5 mg arm, there was al­so a con­trol group tak­ing a TNF in­hibitor.

The FDA sound­ed its own alarm days lat­er, launch­ing an in­ves­ti­ga­tion and urg­ing pa­tients to seek med­ical care if they ex­pe­ri­ence a blood clot in the lung, chest pains, or start cough­ing up blood.

Xel­janz was the orig­i­nal JAK in­hibitor to hit the mar­ket, rack­ing up block­buster sales in the sev­en years it’s been ap­proved by the FDA (the EMA nod came much lat­er in 2017). But safe­ty is­sues have cloud­ed both the drug and the en­tire class, as man­i­fest­ed by the FDA’s de­ci­sion to slap down a high­er, 4 mg dose of Eli Lil­ly’s Olu­mi­ant (baric­i­tinib) and al­low on­ly the 2 mg dose in the mar­ket.

None of that has stopped Pfiz­er from step­ping up its JAK game, though. Just this week, the phar­ma gi­ant tout­ed a pos­i­tive slate of Phase III da­ta for its JAK1 in­hibitor abroc­i­tinib (PF-​04965842) in atopic der­mati­tis, look­ing to get in­to a heat­ed block­buster race.

Ab­b­Vie’s own JAK1, upadac­i­tinib, is now un­der reg­u­la­to­ry re­view for rheuma­toid arthri­tis on both sides of the At­lantic. Gilead put its bet on fil­go­tinib, wide­ly tapped as a po­ten­tial block­buster in its own right. Both com­pa­nies are giv­ing them­selves high marks on safe­ty, sig­nal­ing a fierce mar­ket­ing ri­val­ry to come.


Im­age Source: Pfiz­er

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.

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.

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.

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.

Which top 10 big phar­mas have the most to gain — or lose — over the next 5 years?

When Evaluate Pharma crunched the likely drug sales numbers for the big 10, 2 stood out. 

Takeda, with its big Shire buyout under its belt, is set to almost double its worldwide sales record for 2018 over 5 years, putting it in the big 10 — the 9th spot, to be exact — which is exactly where CEO Christophe Weber wants to be. 

Endpoints News

Basic subscription required

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

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.

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.