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.

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