Thanks to Supreme Court de­ci­sion, Mer­ck gets an­oth­er chance to throw out Fos­amax claims

In a tem­po­rary re­lief for Mer­ck amid on­go­ing le­gal dra­ma sur­round­ing its os­teo­poro­sis drug Fos­amax, the Supreme Court has va­cat­ed the judg­ment of a low­er court and di­rect­ed it to re­con­sid­er a rul­ing that al­lowed law­suits to go to tri­al.

While the jus­tices did not weigh in on the mer­its of those law­suits, the de­ci­sion re­vives Mer­ck’s hopes of throw­ing out hun­dreds of pa­tients claims, which ac­cuse the phar­ma gi­ant of vi­o­lat­ing state laws by ne­glect­ing to warn them of risks as­so­ci­at­ed with Fos­amax for over a decade. Even though sci­en­tists had spec­u­lat­ed that Fos­amax — a bis­pho­s­pho­nate de­signed to pre­vent os­teo­porot­ic frac­tures — could in­crease the risk of atyp­i­cal femoral frac­tures be­fore the FDA ap­proved the drug in 1995, the la­bel did not fea­ture a warn­ing on that score. De­spite sub­se­quent ev­i­dence from pa­tient re­ports con­firm­ing the risk, a warn­ing was not added un­til 2010 fol­low­ing an or­der from reg­u­la­tors.

Why didn’t Mer­ck do any­thing about it dur­ing that time? It’s not for lack of try­ing, the com­pa­ny ar­gues. Rather, its at­tempt to add a warn­ing to the la­bel was re­ject­ed by the FDA, free­ing it of any le­gal re­spon­si­bil­i­ty for fail­ure to warn.

Stephen Brey­er

Key to val­i­dat­ing that ar­gu­ment is a le­gal prin­ci­ple in fed­er­al-state re­la­tions known as pre-emp­tion. In this case — fol­low­ing a 2009 prece­dent set in Wyeth v. Levine — it means that when there is “clear ev­i­dence” that the FDA would not have ap­proved the warn­ing that state law re­quires, the drug man­u­fac­tur­er could not be blamed for fail­ing to com­ply with that state law.

The plain­tiffs might dis­agree on whether that cri­te­ria is met. In fact, Jus­tice Stephen Brey­er ac­knowl­edged in the ma­jor­i­ty opin­ion that the FDA turned down Mer­ck’s pro­posed change on the grounds that it was “in­ad­e­quate” and in­vit­ed them to re­sub­mit an ap­pli­ca­tion to ful­ly ad­dress its de­fi­cien­cies. But that’s up for a judge, not a ju­ry, to de­cide — con­tra­dict­ing the de­ci­sion of the 2017 rul­ing by the Court of Ap­peals for the Third Cir­cuit.

That’s where the case, 17-290 Mer­ck Sharp & Dohme Corp. v. Al­brecht, is head­ed back now.

From the head­note sum­ming up the unan­i­mous rul­ing:

The ques­tion of agency dis­ap­proval is pri­mar­i­ly one of law for a judge to de­cide. The ques­tion of­ten in­volves the use of le­gal skills to de­ter­mine whether agency dis­ap­proval fits facts that are not in dis­pute. More­over, judges, rather than lay ju­ries, are bet­ter equipped to eval­u­ate the na­ture and scope of an agency’s de­ter­mi­na­tion, and are bet­ter suit­ed to un­der­stand and to in­ter­pret agency de­ci­sions in light of the gov­ern­ing statu­to­ry and reg­u­la­to­ry con­text. While con­test­ed brute facts will some­times prove rel­e­vant to a court’s le­gal de­ter­mi­na­tion about the mean­ing and ef­fect of an agency de­ci­sion, such fac­tu­al ques­tions are sub­sumed with­in an al­ready tight­ly cir­cum­scribed le­gal analy­sis and do not war­rant sub­mis­sion alone or to­geth­er with the larg­er pre-emp­tion ques­tion to a ju­ry.

Law­suits against Mer­ck on Fos­amax first emerged around 2009, af­ter the drug had gone gener­ic. It still gar­nered $209 mil­lion in sales last year, ac­cord­ing to fi­nan­cial re­ports.

Im­age source: Shut­ter­stock

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.

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.

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.

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.