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.

Ugur Sahin, BioNTech CEO (Bernd von Jutrczenka/dpa via AP Images)

BioN­Tech is spear­head­ing an mR­NA vac­cine de­vel­op­ment pro­gram for malar­ia, with a tech trans­fer planned for Africa

Flush with the success of its mRNA Covid-19 vaccine, BioNTech is now gearing up for one of the biggest challenges in vaccine development — which comes without potential profit.

The German mRNA pioneer says it plans to work on a jab for malaria, then transfer the tech to the African continent, where it will work with partners on developing the manufacturing ops needed to make this and other vaccines.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 112,900+ biopharma pros reading Endpoints daily — and it's free.

How one start­up fore­told the neu­ro­science re­nais­sance af­ter '50 years of shit­show'

In the past couple of years, something curious has happened: Pharma and VC dollars started gushing into neuroscience research.

Biogen’s controversial new Alzheimer’s drug Aduhelm has been approved on the basis of removing amyloid plaque from the brain, but the new neuro-focused pharma and biotechs have much loftier aims. Significantly curbing or even curing the most notorious disorders would prove the Holy Grail for a complex system that has tied the world’s best drug developers in knots for decades.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Why is On­col­o­gy Drug De­vel­op­ment Re­search Late to the Dig­i­tal Bio­mark­ers Game?

During the recent Annual ASCO Meeting, thousands of cancer researchers and clinicians from across the globe joined together virtually to present and discuss the latest findings and breakthroughs in cancer research and care. There were more than 5000+ scientific abstracts presented during this event, yet only a handful involved the use of motion-tracking wearables to collect digital measures relating to activity, sleep, mobility, functional status, and/or quality of life. Although these results were a bit disappointing, they should come as no surprise to those of us in the wearable technology field.

Art Levinson (Calico)

Google-backed Cal­i­co dou­bles down on an­ti-ag­ing R&D pact with Ab­b­Vie as part­ners ante up $1B, start to de­tail drug tar­gets

Seven years after striking up a major R&D alliance, AbbVie and Google-backed anti-aging specialist Calico are doubling down on their work with a joint, $1 billion commitment to continuing their work together. And they’re also beginning to offer some details on where this project is taking them in the clinic.

According to their statement, each of the two players is putting up $500 million more to keep the labs humming.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 112,900+ biopharma pros reading Endpoints daily — and it's free.

Bob Bradway, Amgen CEO (Scott Eisen/Bloomberg via Getty Images)

Am­gen bel­lies back up to the M&A ta­ble for an­oth­er biotech buy­out, this time with a $2.5B deal for an an­ti­body play­er fo­cused on PS­MA

Five months after Amgen CEO Bob Bradway stepped up to the M&A table and acquired Five Prime for $1.9 billion, following up with the smaller Rodeo acquisition, he’s gone back in for another biotech buyout.

This time around, Amgen is paying $900 million cash while committing up to $1.6 billion in milestones to bag the privately held Teneobio, an antibody drug developer that has expertise in developing new bispecifics and multispecifics. In addition, Amgen cited Teneobio’s “T-cell engager platform, which expands on Amgen’s existing leadership position in bispecific T-cell engagers by providing a differentiated, but complementary, approach to Amgen’s current BiTE platform.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 112,900+ biopharma pros reading Endpoints daily — and it's free.

Eye­ing quick ap­proval, Ab­b­Vie of­fers a close-up on their pres­by­opia drug da­ta

AbbVie picked up some bonus points earlier this year as one of its pipeline adds from the $63 billion Allergan buyout hit its top-line marks. And now the researchers have produced the detailed data on the case they are making with regulators, with an eye on a major new market and a hoped-for approval before New Year’s.

AGN-190584 is aiming to be the first easy-on eyedrop for presbyopia, a common ailment for large numbers of people who find it harder and harder to read things like a watch or cell phone close up. Anyone who’s held a book out at arm’s length in order to read it will be very familiar with the condition, if not the exact diagnosis.

Ryan Watts, Denali CEO

De­nali slips as a snap­shot of ear­ly da­ta rais­es some trou­bling ques­tions on its pi­o­neer­ing blood-brain bar­ri­er neu­ro work

Denali Therapeutics had drummed up considerable hype for their blood-brain barrier technology since launching over six years ago, hype that’s only intensified in the last 14 months following the publications of a pair of papers last spring and proof of concept data earlier this year. On Sunday, the South San Francisco-based biotech gave the biopharma world the next look at in-human data for its lead candidate in Hunter syndrome.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 112,900+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: Pan­el of neu­ro­science ex­perts lays out the com­pli­ca­tions with us­ing Bio­gen's new Alzheimer's drug

Treatment of early Alzheimer’s patients with Biogen’s new drug Aduhelm should closely resemble how the drug was studied in its pivotal clinical trials, according to new recommendations from a panel of neuroscience experts led by UNLV’s Jeffrey Cummings.

“Those considering aducanumab therapy should understand that the expected benefit is slowing of cognitive and functional decline; improvement of the current clinical state is not anticipated,” they wrote Tuesday in The Journal of Prevention of Alzheimer’s Disease, noting that some of their recommendations are more specific or more restrictive than the information provided in the FDA’s prescribing information.

Christophe Weber, Takeda CEO (Kyodo via AP Images)

Take­da flesh­es out CNS pact with pep­tide drug­mak­er, set­ting aside $3.5B in fu­ture mile­stones

One of a suite of drugmakers looking to reinvest in the neuroscience space, Takeda has been aggressive in signing on new partners to help build up its pipeline in that space. But sometimes the best partner is the one you already have.

Takeda will set aside $3.5 billion in future milestones and an undisclosed upfront payment to build out its drug discovery deal with Japanese peptide conjugate maker PeptiDream, adding neurodegeneration to the partnership’s list of CNS targets, the companies said Tuesday.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 112,900+ biopharma pros reading Endpoints daily — and it's free.