Roche flags first case of an­ti-drug an­ti­bod­ies that forced a pa­tient to drop would-be block­buster Hem­li­bra

Roche has raised a warn­ing flag on Hem­li­bra, not­ing the first case where a he­mo­phil­ia pa­tient de­vel­oped an­ti-drug an­ti­bod­ies that made the drug in­ef­fec­tive.

A me­dia con­tact sent a state­ment to me that was orig­i­nal­ly cir­cu­lat­ed on Tues­day. In it, the com­pa­ny stat­ed:

We re­cent­ly learned that a pa­tient in our phase III HAVEN 2 clin­i­cal tri­al de­vel­oped a neu­tral­is­ing an­ti-drug an­ti­body to Hem­li­bra. As with all ther­a­peu­tic pro­teins, there is a po­ten­tial for the de­vel­op­ment of an­ti-drug an­ti­bod­ies with Hem­li­bra, as in­di­cat­ed in the US and EU Hem­li­bra prod­uct la­bels. For this pa­tient, the an­ti-drug an­ti­body re­sult­ed in re­duced ef­fi­ca­cy of Hem­li­bra. The pa­tient and his fam­i­ly have de­cid­ed to dis­con­tin­ue treat­ment with Hem­li­bra, and he will re­sume treat­ment with his pre­vi­ous med­i­cine. 

To date, more than 600 peo­ple with haemophil­ia A have been treat­ed with Hem­li­bra world­wide, in­clud­ing in clin­i­cal tri­als. This is the first con­firmed re­port of a de­tectable an­ti-drug an­ti­body that has im­pact­ed the ef­fi­ca­cy of Hem­li­bra in a per­son with haemophil­ia A. We con­tin­ue to mon­i­tor for the de­vel­op­ment of an­ti-drug an­ti­bod­ies to Hem­li­bra in on­go­ing stud­ies glob­al­ly.

The de­vel­op­ment of an­ti-drug an­ti­bod­ies to Hem­li­bra is dis­tinct from the de­vel­op­ment of in­hibitors to fac­tor VI­II. An­ti-drug an­ti­bod­ies to Hem­li­bra may af­fect whether the med­i­cine works, but they do not change the sever­i­ty of the un­der­ly­ing dis­or­der. On the oth­er hand, for the near­ly one in five peo­ple with haemophil­ia A who de­vel­op in­hibitors to fac­tor VI­II , the in­hibitors not on­ly af­fect the ef­fi­ca­cy of fac­tor VI­II re­place­ment ther­a­pies, but they can al­so af­fect any nat­ur­al fac­tor VI­II in the body. In­hibitors to fac­tor VI­II put peo­ple with haemophil­ia A at greater risk for life-threat­en­ing bleeds or re­peat­ed bleeds that can cause long-term joint dam­age. 

Pa­tient groups — as well as mar­ket ri­vals — have been pay­ing close at­ten­tion to this drug as it be­gins its glob­al roll­out. A few weeks ago or­ga­ni­za­tions in the US and Eu­rope were quick to pick up and post an up­date from Roche not­ing the 5 deaths that have been record­ed among pa­tients tak­ing the drug, adding that none of the deaths — in­clud­ing 2 re­cent deaths — had been di­rect­ly linked to their drug.

Ac­cord­ing to a spokesper­son, 2 deaths were record­ed re­cent­ly which physi­cians linked to a pre-ex­ist­ing con­di­tion in one case and ma­jor vas­cu­lar surgery in an­oth­er. Those cas­es fol­lowed deaths as­so­ci­at­ed with a rec­tal he­m­or­rhage and 2 in­tracra­nial he­m­or­rhages, which ini­tial­ly stirred ear­ly con­cerns about the drug.

Roche has block­buster am­bi­tions for Hem­li­bra, which pos­es a ma­jor threat to ag­ing fran­chis­es at Shire — now be­ing court­ed by Take­da with a $65 bil­lion buy­out agree­ment in place. An­a­lysts have pegged po­ten­tial peak sales at up to $5 bil­lion, mak­ing this drug huge­ly im­por­tant to Roche as it deals with the loss of its three big fran­chise bi­o­log­ics.

Reg­u­la­tors have been help­ful mov­ing this one along, ap­prov­ing the ther­a­py for pa­tients with fac­tor VI­II in­hibitors. Just days ago the FDA added a break­through des­ig­na­tion for the drug for use among pa­tients with­out fac­tor VI­II in­hibitors, point­ing the way to an even big­ger mar­ket.

The crit­i­cal fo­cus here is on get­ting pa­tients who have been sta­ble on Shire’s fac­tor re­place­ment ther­a­py Ad­vate to switch to the new med. But as with any new drug, sta­ble pa­tients may spend a con­sid­er­able amount of time weigh­ing the ar­gu­ments for or against the ther­a­py. Roche record­ed rev­enue of 23 mil­lion Swiss francs for the drug in Q1, say­ing they were pleased by the ear­ly trac­tion they were gain­ing.

Im­age: ROCHE

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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