And then there were 4: Juno adds an­oth­er vic­tim in CAR-T death tal­ly

Juno’s CAR-T drugs didn’t just kill three peo­ple in clin­i­cal tri­als. They ac­tu­al­ly killed 4, as the com­pa­ny notes in its “re­vised” re­marks from last week’s tran­script of a call with com­pa­ny an­a­lysts. And the fol­lowup rais­es the mys­tery of yet an­oth­er case of cere­bral ede­ma trig­gered by se­vere neu­ro­tox­i­c­i­ty, which may or may not have been re­port­ed by Juno.

Here’s the state­ment, post­ed with the tran­script in a fil­ing with the SEC:

Note to Re­vised Re­marks: (Chief Med­ical Of­fi­cer Dr. Mark) Gilbert mis­tak­en­ly said “three” cas­es out of 129 rather than “four” cas­es. The fourth case was a pa­tient treat­ed in the JCAR014 tri­al, which case oc­curred in a young adult pa­tient with r/r ALL who re­ceived flu/cy pre­con­di­tion­ing and a high­er JCAR014 cell dose than is now used on that tri­al. This death was in­clud­ed in the da­ta pre­sent­ed in an oral pre­sen­ta­tion at the Amer­i­can So­ci­ety of Hema­tol­ogy meet­ing in De­cem­ber 2015 and in­clud­ed in Juno’s An­nu­al Re­port on Form 10-K for the fis­cal year end­ed De­cem­ber 31, 2015.

Note to Re­vised Re­marks: As not­ed ear­li­er in the ques­tion and an­swer ses­sion, the FDA al­so re­port­ed an in­stance of cere­bral ede­ma in its data­base out­side of the JCAR015 tri­al. Juno does not know whether that in­stance is the same case of cere­bral ede­ma as Juno is aware of from the JCAR014 tri­al, or if it oc­curred on a tri­al for a non-Juno prod­uct can­di­date.

Juno trig­gered a rout among its in­vestors last week when it stunned the mar­ket with news that its lead CAR-T drug, JCAR015, had killed three peo­ple in clin­i­cal stud­ies, trig­ger­ing a clin­i­cal hold of its piv­otal study by the FDA. The com­pa­ny im­me­di­ate­ly blamed the re­cent ad­di­tion of the chemo drug flu­dara­bine to pre­con­di­tion pa­tients for the cell ther­a­py and of­fered to drop the drug. In one of the fastest re­spons­es by the FDA in the face of mul­ti­ple pa­tient deaths, the agency agreed and lift­ed the hold ear­li­er this week.

The per­son­al­ized brand of CAR-Ts that Juno, Kite, and No­var­tis have been de­vel­op­ing ex­tract im­mune cells from pa­tients, re-en­gi­neer them with a chimeric anti­gen re­cep­tor and then in­ject them back in­to pa­tients, equipped to swarm can­cer cells. These new treat­ments are al­so known to trig­ger cy­tokine re­lease syn­drome, which forced a tem­po­rary pause in the ex­per­i­men­tal work a cou­ple of years ago. But Juno be­lieves that the way that flu­dara­bine was used re­cent­ly caused the neu­ro­tox­i­c­i­ty that trig­gered cas­es of cere­bral ede­ma tracked by in­ves­ti­ga­tors.

Not every­one was as quick as the FDA to buy in­to that the­o­ry, though, as sev­er­al in­ves­ti­ga­tors note that flu­dara­bine has been used reg­u­lar­ly with­out ev­i­dence of cere­bral ede­mas. In ad­di­tion, ri­val Kite Ther­a­peu­tics has used a low dose of flu­dara­bine in its work and has no plans to change as it pur­sues its own piv­otal work.

The FDA, though, is not ex­plain­ing any­thing as of now, de­clin­ing to an­swer some spe­cif­ic ques­tions of mine.

“Cel­lu­lar ther­a­pies, in­clud­ing Chimeric Anti­gen Re­cep­tor (CAR) T-Cell ther­a­pies, hold great promise in the treat­ment of se­ri­ous and life-threat­en­ing dis­eases,” the agency said in a state­ment to End­points. “We there­fore do every­thing pos­si­ble to as­sist spon­sors in ad­vanc­ing clin­i­cal de­vel­op­ment pro­grams in an ef­fort to bring promis­ing ther­a­pies to pa­tients. The FDA rec­og­nizes that in­ves­ti­ga­tion­al prod­ucts in­tend­ed to treat se­ri­ous dis­eases al­so have the po­ten­tial to pose risks to pa­tients. To this end, the FDA con­stant­ly looks at the risk-ben­e­fit pro­file of ex­per­i­men­tal ther­a­pies and when we have con­cerns about the risks, we may place the clin­i­cal tri­als on hold.”

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.

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.

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.

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.

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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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.

Why would the FDA ap­prove an­oth­er con­tro­ver­sial drug to spur a woman’s li­bido with these da­ta? And why no ex­pert pan­el re­view?

AMAG Pharmaceuticals’ newly approved drug for spurring women’s sexual desire may never make much money, but it’s a big hit at sparking media attention.

The therapy — Vyleesi (bremelanotide) — got the green light from regulators on Friday evening, swiftly lighting up a range of stories around the world, from The New York Times to The Guardian. Several headlines inevitably referred to it as the “female Viagra,” invoking Pfizer’s old erectile dysfunction blockbuster.

But the two drugs have little in common.

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