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.

Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

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UP­DAT­ED: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology
ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development
CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at help@endpointsnews.com with any issues.

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Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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Bob Smith, Pfizer

Pfiz­er is mak­ing a $500M state­ment to­day: Here’s how you be­come a lead play­er in the boom­ing gene ther­a­py sec­tor

Three years ago, Pfizer anted up $150 million in cash to buy Bamboo Therapeutics in Chapel Hill, NC as it cautiously stuck a toe in the small gene therapy pool of research and development.

Company execs followed up a year later with a $100 million expansion of the manufacturing operations they picked up in that deal for the UNC spinout, which came with $495 million in milestones.

And now they’re really going for it.

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Video: Putting the AI in R&D — with Badhri Srini­vasan, Tony Wood, Rosana Kapeller, Hugo Ceule­mans, Saurabh Sa­ha and Shoibal Dat­ta

During BIO this year, I had a chance to moderate a panel among some of the top tech experts in biopharma on their real-world use of artificial intelligence in R&D. There’s been a lot said about the potential of AI, but I wanted to explore more about what some of the larger players are actually doing with this technology today, and how they see it advancing in the future. It was a fascinating exchange, which you can see here. The transcript has been edited for brevity and clarity. — John Carroll

UP­DAT­ED: As­traZeneca’s Imfinzi/treme com­bo strikes out — again — in lung can­cer. Is it time for last rites?

AstraZeneca bet big on the future of their PD-L1 Imfinzi combined with the experimental CTLA-4 drug tremelimumab. But once again it’s gone down to defeat in a major Phase III study — while adding damage to the theory involving targeting cancer with a high tumor mutational burden.

Early Wednesday the pharma giant announced that their NEPTUNE study had failed, with the combination unable to beat standard chemo at overall survival in high TMB cases of advanced non-small cell lung cancer. We won’t get hard data until later in the year, but the drumbeat of failures will call into question what — if any — future this combination can have left.

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Am­gen, Al­ler­gan biosim­i­lar of Roche's block­buster Rit­ux­an clears an­oth­er US piv­otal study 

Novartis $NVS may have given up, but Amgen $AMGN and Allergan $AGN are plowing ahead with their knockoff of Roche’s blockbuster biologic Rituxan in the United States.

Their copycat, ABP 798, was found to have a clinically equivalent impact as Rituxan — meeting the main goal of the study involving CD20-positive B-cell non-Hodgkin’s lymphoma patients. This is the second trial supporting the profile of the biosimilar. In January, it came through with positive PK results in patients with rheumatoid arthritis.

BeiGene and Mus­tang nail down spe­cial FDA sta­tus for top drugs; Roche bags added cov­er­age for Hem­li­bra

→ BeiGene $BGNE is getting a boost in its drive to field a rival to Imbruvica. The FDA has offered an accelerated review to zanubrutinib, a BTK inhibitor that has posted positive results for mantle cell lymphoma. The PDUFA date lands on February 27, 2020. The drug scored breakthrough status at the beginning of the year.

→ BeiGene isn’t the only biopharma company to gain special regulatory status today. Mustang Bio $MBIO and St. Jude Children’s Research Hospital announced that MB-107, a lentiviral gene therapy for the treatment of X-linked severe combined immunodeficiency, also known as bubble boy disease, has been granted Regenerative Medicine Advanced Therapy status.