New Lis­te­ria fears spot­light­ed as Aduro’s CRS-207 is slapped with par­tial hold

Aduro CEO Stephen Isaacs

Nag­ging fears that Aduro Biotech’s can­cer vac­cine CRS-207 could trig­ger se­ri­ous Lis­te­ria in­fec­tions mush­roomed in­to a se­vere set­back on Mon­day morn­ing as the biotech re­port­ed that it had to halt en­roll­ment in all of its clin­i­cal stud­ies us­ing that tech­nol­o­gy. The par­tial hold was in­sti­tut­ed by the FDA af­ter a pa­tient test­ed pos­i­tive for Lis­te­ria, which is sus­pect­ed to be CRS-207, Aduro’s lead can­cer vac­cine.

CRS-207 is made up of reengi­neered Lis­te­ria mono­cy­to­genes — re­mov­ing genes in or­der to dis­arm the bac­te­ria — that ex­press mesothe­lin, spark­ing an im­mune re­sponse to a pro­tein con­cen­trat­ed on can­cer cells. Aduro has matched it with an­oth­er can­cer vac­cine, GVAX, hop­ing to pro­vide a one-two punch against can­cer, with an op­tion to add on ad­di­tion­al drugs to con­tin­ue to build an at­tack on can­cer cells.

Aduro’s shares $ADRO were ham­mered ear­li­er this year by the fail­ure of a com­bo study for pan­cre­at­ic can­cer. And the stock dropped 12% in pre-mar­ket trad­ing on Mon­day.

This isn’t the first time that Aduro has had to deal with Lis­te­ria fears. Last fall its stock briefly tum­bled when a pa­tient tak­ing the ther­a­py — which is sup­posed to be reengi­neered to pre­vent in­fec­tions — de­vel­oped Lis­te­ria. That news was dis­closed in a SEC fil­ing, trig­ger­ing fears that a hold could be on the way for Aduro. This sec­ond case rais­es fresh con­cerns that the drug may not have been com­plete­ly dis­armed, as promised.

The new set­back came as a sur­prise to a num­ber of an­a­lysts, who had ex­pect­ed that Aduro would be re­port­ing re­sults from a triple com­bo study of CRS-207, GVAX and Bris­tol-My­ers Squibb’s Op­di­vo for pan­cre­at­ic can­cer. That tri­al and oth­ers which are ful­ly en­rolled will con­tin­ue on sched­ule. Tri­als that have been de­layed in­clude a Phase I ovar­i­an can­cer study as well as a glioblas­toma tri­al.

In a call with an­a­lysts, CEO Stephen Isaacs heav­i­ly em­pha­sized that this is a par­tial hold af­ter the sec­ond Lis­te­ria case seen in 350 treat­ed pa­tients. R&D chief Dirk Brock­st­edt added that the com­pa­ny be­lieves that it’s “like­ly” that the strain dis­cov­ered in the fe­male pa­tient is ‘207. And both em­pha­sized that they are prepar­ing to in­sti­tute changes to the tri­al, in­clud­ing a mod­i­fi­ca­tion of the tri­al pro­to­cols with a re­vi­sion in an­tibi­ot­ic treat­ment and their sur­veil­lance of the pa­tients af­ter treat­ment.

“We’re op­ti­mistic this is go­ing to be re­solved and we’re do­ing all we can to re­solve it,” Isaacs summed up.

Lis­te­ria was de­tect­ed on an “in­dwelling port” used on de­vices, and some an­a­lysts are spec­u­lat­ing that pa­tients with such ports are like­ly to be barred from treat­ment to re­duce the risk of in­fec­tion.

In their state­ment, Aduro re­port­ed:

Aduro is work­ing with the FDA to lift the par­tial hold so as to re­sume new pa­tient en­roll­ment in its LADD clin­i­cal tri­als. The com­pa­ny is re­vis­ing study pro­to­cols in ac­cor­dance with feed­back from the agency, in­clud­ing the mod­i­fi­ca­tion of an­tibi­ot­ic ad­min­is­tra­tion fol­low­ing treat­ment, ex­tend­ed pa­tient sur­veil­lance, and, as a pre-emp­tive mea­sure, ex­clu­sion of pa­tients who are on or will re­ceive cer­tain im­mune-sup­pres­sive treat­ments or who have cer­tain pros­thet­ic de­vices. Aduro will be pro­vid­ing pro­posed re­vi­sions to the pro­to­cols, pa­tient con­sent forms, and in­ves­ti­ga­tor brochures to the agency lat­er this week.

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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