Sanders, Cum­mings prob­ing FDA’s han­dling of Marathon af­ter a con­tro­ver­sial OK of old steroid for Duchenne MD

Rep. Eli­jah Cum­mings (D-MD)

Ver­mont Sen­a­tor Bernie Sanders and Rep. Eli­jah Cum­mings are tak­ing di­rect aim at the FDA to­day, crit­i­ciz­ing the agency for its red-car­pet treat­ment of Marathon Phar­ma­ceu­ti­cals as the bio­phar­ma com­pa­ny wound its way through the reg­u­la­to­ry re­view process, pick­ing up a lu­cra­tive ap­proval to use a cheap, gener­ic steroid as a high-priced brand­ed ther­a­py specif­i­cal­ly for Duchenne mus­cu­lar dy­s­tro­phy af­ter repack­ag­ing da­ta more than 20 years old.

The FDA has said be­fore that they sim­ply fol­lowed the rules in the way it han­dled this drug, OK’d as Em­flaza. But Sanders and Cum­mings, who has been lead­ing the charge in Con­gress to push Medicare to start ne­go­ti­at­ing drug prices, want to know if the FDA has a plan in mind to guard against com­pa­nies that want to game the sys­tem in search of big and easy prof­its. And they’re ask­ing the FDA for records that could ex­plain Marathon’s treat­ment, while point­ed­ly push­ing reg­u­la­tors to avoid a re­peat.

In ad­di­tion, the let­ter sug­gests that Marathon isn’t done ma­nip­u­lat­ing the sys­tem. The com­pa­ny has al­so ob­tained an or­phan in­di­ca­tion for de­flaza­cort as a treat­ment for pe­di­atric arthri­tis, the law­mak­ers say, putting it on track to po­ten­tial­ly ex­tend its stretch of mar­ket ex­clu­siv­i­ty and en­hance the drug’s fran­chise val­ue.

On Thurs­day morn­ing, though, Marathon an­nounced a sur­prise deal to sell de­flaza­cort to long­time Duchenne play­er PTC Ther­a­peu­tics for $140 mil­lion plus roy­al­ties. And the law­mak­ers may now have to shift their fo­cus as Marathon ex­ecs shun the spot­light. But the con­tro­ver­sy is un­like­ly to end, es­pe­cial­ly as PTC will now come up with a new price which is al­so like­ly to out­rage the Duchenne com­mu­ni­ty. And reg­u­la­tors will have to en­dure some ad­di­tion­al scruti­ny as well.

“A re­view of a num­ber of the doc­u­ments re­lat­ed to the orig­i­nal Uni­ver­si­ty of Rochester ap­pli­ca­tion for or­phan drug sta­tus and ear­li­er clin­i­cal tri­als has raised se­ri­ous ques­tions about FDA’s de­ci­sion re­gard­ing Em­flaza….” they write in the let­ter. “The fact that FDA award­ed Marathon a PRV and or­phan drug sta­tus with­out the com­pa­ny con­duct­ing sig­nif­i­cant re­search of its own un­der­mines the goals of these in­cen­tives. What process­es does FDA have in place to en­sure pri­vate com­pa­nies are not ma­nip­u­lat­ing a sys­tem meant to in­cen­tivize re­search for treat­ments of ex­treme­ly vul­ner­a­ble pa­tient pop­u­la­tions?”

What fol­lows is a laun­dry list of ques­tions for act­ing com­mis­sion­er Stephen Os­troff, in­clud­ing:

— Is it stan­dard prac­tice for FDA to re­ly on 20-year-old ef­fi­ca­cy da­ta and, if so, how many times has this hap­pened in the last 15 years?  If this is not a stan­dard prac­tice, is Em­flaza’s ap­proval an ex­cep­tion?

— Did any FDA em­ploy­ees raise any con­cerns about grant­i­ng Marathon the ben­e­fits of or­phan drug sta­tus or a PRV (pri­or­i­ty re­view vouch­er) for Em­flaza? Please pro­vide copies of mem­os, e-mails, or records of any such cor­re­spon­dence or doc­u­men­ta­tion.

The law­mak­ers’ staff al­so tracked the own­er­ship of the de­flaza­cort da­ta, not­ing that the work was orig­i­nal­ly fund­ed by Mar­i­on Mer­rell Dow, which merged, merged again and even­tu­al­ly wound up un­der the con­trol of Sanofi. From the let­ter:

— Giv­en this lengthy chain, what ev­i­dence did Marathon present to FDA re­gard­ing the in­tegri­ty of the decades-old ef­fi­ca­cy tri­al da­ta?  What in­for­ma­tion does FDA have re­gard­ing how Marathon came to ob­tain the 1995 da­ta?  Did FDA take any steps to ver­i­fy the va­lid­i­ty or in­tegri­ty of the chain of cus­tody of this in­for­ma­tion or ver­i­fy the old da­ta?  Please ex­plain.

The law­mak­ers picked over a string of sto­ries on the is­sue, in­clud­ing ar­ti­cles I’ve writ­ten about the es­ti­mat­ed price of de­vel­op­ment and more.

So far, most of the heat gen­er­at­ed by the con­tro­ver­sy over Marathon’s de­flaza­cort ap­proval has been di­rect­ed at the com­pa­ny and its CEO, Jeff Aronin. Sanders, an out­spo­ken crit­ic of the phar­ma in­dus­try’s pric­ing prac­tices, is spear­head­ing a dif­fer­ent kind of at­tack to­day aimed at reg­u­la­tors who hand­ed Marathon every plum a de­vel­op­er could want. And he’s clear­ly wrapped it in the kind of barbed lan­guage that would make it less like­ly for reg­u­la­tors to do it again, for an­oth­er com­pa­ny.

The sto­ry about Marathon and its cam­paign on de­flaza­cort has trig­gered a hot-tem­pered re­sponse among a va­ri­ety of De­mo­c­ra­t­ic law­mak­ers who see this as yet an­oth­er ex­am­ple of the kind of price goug­ing that a grow­ing list of bio­phar­ma com­pa­nies have en­gaged in. And this one is a stand­out.

De­flaza­cort is an old steroid that’s sold out­side the US for rheuma­toid arthri­tis and all the usu­al af­flic­tions as­so­ci­at­ed with steroid use. A num­ber of par­ents in the US have been buy­ing it from a UK sup­pli­er for about $1,000 a year, sat­is­fied that it’s the best choice for strength­en­ing chil­dren crip­pled and even­tu­al­ly killed by Duchenne mus­cu­lar dy­s­tro­phy, par­tic­u­lar­ly as it’s linked to less weight gain than ri­vals.

Marathon, though, priced de­flaza­cort at $89,000 a year af­ter the FDA ap­proved it, trig­ger­ing a tem­pest in the Duchenne com­mu­ni­ty. The com­pa­ny main­tained that it did the “heavy lift­ing” re­quired for a US ap­proval, cit­ing its re­search pro­gram and vow­ing that they would need years of sales to re­coup their in­vest­ment. But the tri­al ex­perts we talked to came up with de­vel­op­ment bud­gets that would make this drug quick­ly prof­itable, even with just a frac­tion of the mar­ket.

Along the way, the FDA re­ward­ed Marathon with some ma­jor ad­van­tages. There was an or­phan des­ig­na­tion, which comes with sev­en years of mar­ket ex­clu­siv­i­ty. There was al­so a pri­or­i­ty re­view vouch­er which can now be sold for more than $100 mil­lion — the vouch­ers, which can cut four months off of any drug re­view, have fetched as much as $350 mil­lion — which could eas­i­ly be enough to pay for the en­tire de­vel­op­ment pro­gram by it­self.

The out­cry has forced Marathon to pull back, at least tem­porar­i­ly paus­ing the launch of de­flaza­cort while talk­ing it over with mem­bers of the close­ly-knit Duchenne com­mu­ni­ty. It’s un­like­ly, though, that it can come up with a price like­ly to sat­is­fy par­ents al­ready pay­ing a dis­count price for over­seas sup­plies.

The FDA in the past has said that it han­dled this case as it would any oth­er, guid­ed by the rules laid out by Con­gress. Sanders, though, says the FDA got played, and he wants it to stop.

Pres­i­dent Trump re­cent­ly named Scott Got­tlieb as the head of the FDA. And if he gets the Sen­ate nod, as ex­pect­ed, he can set­tle in with a con­tro­ver­sy sit­ting on his desk.

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.

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 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.

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.