Faced with fresh con­cerns about Hem­li­bra’s safe­ty, Roche spells out what it knows about 5 deaths

Roche is of­fer­ing some ad­di­tion­al de­tails on the 5 deaths they’ve record­ed among he­mo­phil­ia pa­tients tak­ing Hem­li­bra, re­peat­ing their as­ser­tion that the risk/ben­e­fit pro­file of the would-be block­buster re­mains un­changed as they con­duct an “on­go­ing” in­ves­ti­ga­tion of two re­cent cas­es.

Ac­cord­ing to a spokesper­son, 2 new 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 two in­tracra­nial he­m­or­rhages.

News of the death tal­ly, which spread like wild fire af­ter Roche sent out a state­ment to pa­tient groups, reignit­ed lin­ger­ing safe­ty con­cerns about the drug, which an­a­lysts be­lieve has been on track to rack up $4 bil­lion to $5 bil­lion in an­nu­al sales.

David Stein­berg

Jef­feries an­a­lyst David Stein­berg high­light­ed the state­ment from Roche and some con­tin­ued puz­zle­ment over the drug’s mech­a­nism of ac­tion, writ­ing that these new­ly re­port­ed deaths could arouse fresh safe­ty con­cerns. He not­ed:

It is Pos­si­ble that Con­cerns Over Hem­li­bra’s Safe­ty Could Now Reemerge Amongst Clin­i­cians and Pa­tients: Im­por­tant­ly, the NHA – which re­ceived in­for­ma­tion from Roche’s clin­i­cal de­vel­op­ment lead on March 26 – fur­ther in­di­cat­ed that these deaths have all ap­par­ent­ly been deemed un­re­lat­ed to Hem­li­bra by in­ves­ti­ga­tors or treat­ing physi­cians. How­ev­er, giv­en the pre­vi­ous­ly re­port­ed death and cas­es of throm­boem­bol­ic events and throm­bot­ic mi­croan­giopa­thy ob­served dur­ing clin­i­cal test­ing in a rel­a­tive­ly small num­ber of pa­tients – at­trib­uted to the con­cur­rent use of Hem­li­bra with by­pass­ing agents (Fei­ba/No­vo 7) dur­ing break­through bleed­ing episodes – it is not en­tire­ly sur­pris­ing to see ad­di­tion­al dis­clo­sures of se­ri­ous ad­di­tion­al ad­verse events, in­clud­ing un­for­tu­nate­ly – deaths. And with very lim­it­ed in­for­ma­tion, it is un­clear if there are ad­di­tion­al safe­ty con­cerns with Hem­li­bra at this point. How­ev­er, it’s a pos­si­bil­i­ty that height­ened con­cerns – which arose af­ter the ini­tial death in the HAVEN 1 study – could re­merge. Ad­di­tion­al­ly, we’d note that some ex­perts still do not ful­ly un­der­stand the mech­a­nism be­hind Hem­li­bra, which could po­ten­tial­ly im­pact use in non-in­hibitor pa­tients who are gen­er­al­ly well con­trolled on SH­PG’s Ad­vate.

And for its part, Shire — fac­ing a ma­jor ri­val to a key fran­chise pro­gram — has stoked fears as well, claim­ing ear­li­er that Roche has made “in­ac­cu­rate and mis­lead­ing” state­ments about the se­ri­ous ad­verse events tracked in its Phase III.

Ac­cord­ing to the spokesper­son for Roche, here’s what they know about the deaths:

— In 2017, the adult pa­tient in the Phase III HAVEN 1 tri­al ex­pe­ri­enced a se­ri­ous rec­tal he­m­or­rhage, which the in­ves­ti­ga­tor as­sessed as the cause of death, un­re­lat­ed to Hem­li­bra.

— Three deaths have been re­port­ed to Genen­tech in adult pa­tients tak­ing Hem­li­bra through re­quests to Roche for com­pas­sion­ate use.

— In 2016, an adult pa­tient tak­ing Hem­li­bra through a re­quest for com­pas­sion­ate use passed away due to an in­tracra­nial he­m­or­rhage and wide­spread bac­te­r­i­al in­fec­tion, which the treat­ing physi­cian as­sessed as the cause of death, un­re­lat­ed to Hem­li­bra.

— In 2017, an adult pa­tient tak­ing Hem­li­bra through a re­quest for com­pas­sion­ate use passed away. The pa­tient had suf­fered mul­ti­ple in­tracra­nial he­m­or­rhages in the past due to pre­dis­pos­ing fac­tors, pri­or to start­ing Hem­li­bra. The treat­ing physi­cian’s as­sess­ment was that the cause of death was due to an in­tracra­nial he­m­or­rhage, and it was un­re­lat­ed to Hem­li­bra.

— We just re­cent­ly learned that a third adult pa­tient tak­ing Hem­li­bra through a re­quest for com­pas­sion­ate use passed away. The treat­ing physi­cian’s as­sess­ment was that the cause of death was due to a pre-ex­ist­ing med­ical con­di­tion, and it was un­re­lat­ed to Hem­li­bra. It was re­port­ed that the pa­tient had been en­rolled in the com­pas­sion­ate use pro­gram due to a med­ical emer­gency re­lat­ed to an ab­dom­i­nal pseu­do-tu­mor and passed away from com­pli­ca­tions re­lat­ed to this pre-ex­ist­ing con­di­tion.

— We just re­cent­ly learned that a fifth adult pa­tient tak­ing Hem­li­bra passed away. It was re­port­ed that the pa­tient passed away sev­er­al weeks fol­low­ing an elec­tive ma­jor vas­cu­lar surgery. The treat­ing physi­cian’s as­sess­ment was that the pa­tient’s death was un­re­lat­ed to Hem­li­bra.

Our in­ves­ti­ga­tion and as­sess­ment of these two re­cent events is cur­rent­ly on­go­ing. We un­der­stand the ur­gency of re­view­ing and as­sess­ing safe­ty events, and it is a pri­or­i­ty for us to share ac­cu­rate in­for­ma­tion about the safe­ty of Hem­li­bra that is based on a thor­ough as­sess­ment. We will work dili­gent­ly to pro­vide ap­pro­pri­ate up­dates as quick­ly as pos­si­ble, while en­sur­ing the con­fi­den­tial­i­ty of the pa­tients is re­spect­ed. As men­tioned pre­vi­ous­ly, based on these as­sess­ments and the avail­able in­for­ma­tion, these events do not change the cur­rent­ly known ben­e­fit/risk pro­file of Hem­li­bra.

We’ll keep you post­ed as any new de­tails come in. It’s un­like­ly the safe­ty spot­light will fade any­time soon.

The top 10 block­buster drugs in the late-stage pipeline — Eval­u­ate adds 6 new ther­a­pies to heavy-hit­ter list

Vertex comes in for a substantial amount of criticism for its no-holds-barred tactical approach toward wresting the price it wants for its commercial drugs in Europe. But the flip side of that coin is a highly admired R&D and commercial operation that regularly wins kudos from analysts for their ability to engineer greater cash flow from the breakthrough drugs they create.

Both aspects needed for success in this business are on display in the program backing Vertex’s triple for cystic fibrosis. VX-659/VX-445 + Tezacaftor + Ivacaftor — it’s been whittled down to 445 now — was singled out by Evaluate Pharma as the late-stage therapy most likely to win the crown for drug sales in 5 years, with a projected peak revenue forecast of $4.3 billion.

The latest annual list, which you can see here in their latest world preview, includes a roster of some of the most closely watched development programs in biopharma. And Evaluate has added 6 must-watch experimental drugs to the top 10 as drugs fail or go on to a first approval. With apologies to the list maker, I revamped this to rank the top 10 by projected 2024 sales, instead of Evaluate's net present value rankings.

It's how we roll at Endpoints News.

Here is a quick summary of the rest of the top 10:

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John Reed at JPM 2019. Jeff Rumans for Endpoints News

Sanofi's John Reed con­tin­ues to re­or­ga­nize R&D, cut­ting 466 jobs while boost­ing can­cer, gene ther­a­py re­search

The R&D reorganization inside Sanofi is continuing, more than a year after the pharma giant brought in John Reed to head the research arm of the Paris-based company.
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How small- to mid-sized biotechs can adopt pa­tient cen­tric­i­ty in their on­col­o­gy tri­als

By Lucy Clos­sick Thom­son, Se­nior Di­rec­tor of On­col­o­gy Pro­ject Man­age­ment, Icon

Clin­i­cal tri­als in on­col­o­gy can be cost­ly and chal­leng­ing to man­age. One fac­tor that could re­duce costs and re­duce bar­ri­ers is har­ness­ing the pa­tient voice in tri­al de­sign to help ac­cel­er­ate pa­tient en­roll­ment. Now is the time to adopt pa­tient-cen­tric strate­gies that not on­ly fo­cus on pa­tient needs, but al­so can main­tain cost ef­fi­cien­cy.

In­vestor day prep at Mer­ck in­cludes a new strat­e­gy to pick up the pace on M&A — re­port

Mer­ck’s re­cent deals to buy up two bolt-on biotechs — Ti­los and Pelo­ton — weren’t an aber­ra­tion. In­stead, both ac­qui­si­tions mark a new strat­e­gy to beef up its dom­i­nant can­cer drug op­er­a­tions cen­tered on Keytru­da while look­ing to ad­dress grow­ing con­cerns that too many of its eggs are in the one I/O bas­ket for their PD-1 pro­gram. And Mer­ck is go­ing af­ter more small- and mid-sized buy­outs to calm those fears.

John Chiminski, Catalent CEO - File Photo

'It's a growth play': Catal­ent ac­quires Bris­tol-My­er­s' Eu­ro­pean launch pad, ex­pand­ing glob­al CD­MO ops

Catalent is staying on the growth track.

Just two months after committing $1.2 billion to pick up Paragon and take a deep dive into the sizzling hot gene therapy manufacturing sector, the CDMO is bouncing right back with a deal to buy out Bristol-Myers’ central launchpad for new therapies in Europe, acquiring a complex in Anagni, Italy, southwest of Rome, that will significantly expand its capacity on the continent.

There are no terms being offered, but this is no small deal. The Anagni campus employs some 700 staffers, and Catalent is planning to go right in — once the deal closes late this year — with a blueprint to build up the operations further as they expand on oral solid, biologics, and sterile product manufacturing and packaging.

This is an uncommon deal, Catalent CEO John Chiminski tells me. But it offers a shortcut for rapid growth that cuts years out of developing a green fields project. That’s time Catalent doesn’t have as the industry undergoes unprecedented expansion around the world.

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Right back at you, Pfiz­er: BeiGene and a Pfiz­er spin­out launch a new­co to de­vel­op a MEK/BRAF in­hibitor that could ri­val $11.4B com­bo

A day af­ter Pfiz­er bought Ar­ray and its ap­proved can­cer com­bo, BeiGene and Pfiz­er spin­out Spring­Works have part­nered in launch­ing a new biotech that has an eye on the very same mar­ket the phar­ma gi­ant just paid bil­lions for. And they’re plan­ning on us­ing an ex-Pfiz­er drug to do it.

In a nut­shell, Chi­na’s BeiGene is toss­ing in a pre­clin­i­cal BRAF in­hibitor — BGB-3245, which cov­ers both V600 and non-V600 BRAF mu­ta­tions — for a big stake in a new, joint­ly con­trolled biotech called Map­Kure with Bain-backed Spring­Works.

Sanofi aligns it­self with Google to stream­line drug de­vel­op­ment

Tech­nol­o­gy is bleed­ing in­to health­care, and big phar­ma is rid­ing the wave. Sanofi $SNY ap­point­ed its first chief dig­i­tal of­fi­cer this Feb­ru­ary, fol­low­ing the foot­steps of its peers. By May, the French drug­mak­er and some of its big phar­ma com­pa­tri­ots joined forces with Google par­ent Al­pha­bet’s Ver­i­ly unit to aug­ment clin­i­cal tri­al re­search. On Tues­day, the Parisian com­pa­ny tied up with Google to ac­cess its cloud com­put­ing and ar­ti­fi­cial in­tel­li­gence tech to spur the de­vel­op­ment of new ther­a­pies.

UP­DAT­ED: Roche fields first ap­proval for Ro­z­lytrek in the run-up to a show­down with Bay­er, Pfiz­er

While it’s wait­ing to hear back from FDA reg­u­la­tors, Roche is be­gin­ning the vic­to­ry lap for en­trec­tinib in Japan.

Roche is giv­ing Bay­er a run for their mon­ey with this tu­mor-ag­nos­tic drug, which tar­gets NTRK gene fu­sions. Now dubbed Ro­z­lytrek, it’s sanc­tioned to treat adult and pe­di­atric pa­tients in Japan with neu­rotroph­ic ty­ro­sine re­cep­tor ki­nase fu­sion-pos­i­tive, ad­vanced re­cur­rent sol­id tu­mors.

Arc­turus ex­pands col­lab­o­ra­tion, adding $30M cash; Ku­ra shoots for $100M raise

→  Rare dis­ease play­er Ul­tragenyx $RARE is ex­pand­ing its al­liance with Arc­turus $ARCT, pay­ing $24 mil­lion for eq­ui­ty and an­oth­er $6 mil­lion in an up­front as the two part­ners ex­pand their col­lab­o­ra­tion to in­clude up to 12 tar­gets. “This ex­pand­ed col­lab­o­ra­tion fur­ther so­lid­i­fies our mR­NA plat­form by adding ad­di­tion­al tar­gets and ex­pand­ing our abil­i­ty to po­ten­tial­ly treat more dis­eases,” said Emil Kakkis, the CEO at Ul­tragenyx. “We are pleased with the progress of our on­go­ing col­lab­o­ra­tion. Our most ad­vanced mR­NA pro­gram, UX053 for the treat­ment of Glyco­gen Stor­age Dis­ease Type III, is ex­pect­ed to move in­to the clin­ic next year, and we look for­ward to fur­ther build­ing up­on the ini­tial suc­cess of this part­ner­ship.”