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.

De­vel­op­ment of the Next Gen­er­a­tion NKG2D CAR T-cell Man­u­fac­tur­ing Process

Celyad’s view on developing and delivering a CAR T-cell therapy with multi-tumor specificity combined with cell manufacturing success
Overview
Transitioning potential therapeutic assets from academia into the commercial environment is an exercise that is largely underappreciated by stakeholders, except for drug developers themselves. The promise of preclinical or early clinical results drives enthusiasm, but the pragmatic delivery of a therapy outside of small, local testing is most often a major challenge for drug developers especially, including among other things, the manufacturing challenges that surround the production of just-in-time and personalized autologous cell therapy products.

Paul Hudson, Getty Images

UP­DAT­ED: Sanofi CEO Hud­son lays out new R&D fo­cus — chop­ping di­a­betes, car­dio and slash­ing $2B-plus costs in sur­gi­cal dis­sec­tion

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy presentation Tuesday with a tell-tale deal to buy Synthorx for $2.5 billion. That fits squarely with hints that he’s pointing the company to a bigger future in oncology, which also squares with a major industry tilt.

In a big reveal later in the day, though, Hudson offered a slate of stunners on his plans to surgically dissect and reassemble the portfoloio, saying that the company is dropping cardio and diabetes research — which covers two of its biggest franchise arenas. Sanofi missed the boat on developing new diabetes drugs, and now it’s pulling out entirely. As part of the pullback, it’s dropping efpeglenatide, their once-weekly GLP-1 injection for diabetes.

“To be out of cardiovascular and diabetes is not easy for a company like ours with an incredibly proud history,” Hudson said on a call with reporters, according to the Wall Street Journal. “As tough a choice as that is, we’re making that choice.”

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What does $6.9B buy these days in on­col­o­gy R&D? As­traZeneca has a land­mark an­swer

Given the way the FDA has been whisking through new drug approvals months ahead of their PDUFA date, AstraZeneca and their partners Daiichi Sankyo may not have to wait until Q2 of next year to get a green light on trastuzumab deruxtecan (DS-8201).

The pharma giant this morning played their ace in the hole, showing off why they were willing to commit to a $6.9 billion deal — with $1.35 billion in a cash upfront — to partner on the drug.

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Large advertisements for the drug Vivitrol decorate the walls of Grand Central Station on June 15, 2017 in New York City. (Photo: Andrew Lichtenstein via Getty)

FDA slaps down Alk­er­mes for mis­lead­ing Viv­it­rol ads — don't for­get vul­ner­a­bil­i­ty to opi­oid over­dose

The ads piqued interest as soon as they started appearing in 2016: at Grand Central Station, on the Red Line in Cambridge, and on a billboard off the New Jersey Turnpike. All showed a young person, generally with his or her arms crossed, and the question, “what is Vivitrol?”

Vivitrol’s maker, Alkermes, was in the midst of a marketing and lobbying campaign to promote the anti-opioid addiction drug — a campaign that would face significant backlash for tarnishing competitors despite little evidence for Vivitrol’s superiority.

Paul Hudson, Sanofi

Paul Hud­son promis­es a bright new fu­ture at Sanofi, kick­ing loose me-too drugs and fo­cus­ing on land­mark ad­vances. But can he de­liv­er?

Paul Hudson was on a mission Tuesday morning as he stood up to address Sanofi’s new R&D and business strategy.

Still fresh into the job, the new CEO set out to convince his audience — including the legions of nervous staffers inevitably devoting much of their day to listening in — that the pharma giant is shedding the layers of bureaucracy that had held them back from making progress in the past, dropping the duds in the pipeline and reprioritizing a more narrow set of experimental drugs that were promised as first-in-class or best-in-class.  The company, he added, is now positioned to “go after other opportunities” that could offer a transformational approach to treating its core diseases.

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FDA in-house re­view spot­lights an is­sue with one of Hori­zon's end­points but notes ef­fi­ca­cy for lead drug

The FDA in-house review highlights a disagreement of investigators’ use of a key endpoint by Horizon Pharma in the late-stage trial for the top drug in its pipeline, but largely agreed that the antibody was effective.

Horizon submitted a BLA for thyroid eye disease (TED) drug teprotumumab in March, less than two years after they bought the drug (and the rest of a division) from Narrow River for $145 million upfront. With breakthrough status, priority review, orphan designation and in-house sales projections of up to $750 million, the one-time Roche reject became the marquee pipeline asset for a company that’s developed some of the world’s most expensive drugs.

Seat­tle Ge­net­ics de­tails pos­i­tive OS and PFS da­ta for tu­ca­tinib in breast can­cer

Seattle Genetics $SGEN is showing off more positive data around tucatinib, its pivotal-stage drug for HER2 positive breast cancer.

A month after hearing about solidly upbeat hazard ratios, we learned today that the estimated progression-free survival rate at one year was 33% in the tucatinib arm compared to 12% for patients taking trastuzumab and capecitabine alone.

Median PFS was 7.8 months (95% CI: 7.5, 9.6) in the tucatinib arm, compared to 5.6 months (95% CI: 4.2, 7.1) in the control arm.

Bat­tered, cash hun­gry In­tec feels the burn of No­var­tis re­jec­tion

It’s a case of some bad timing for Intec.

Just when a key trial testing the company’s Accordion drug delivery tech imploded in Parkinson’s disease, they handed Novartis data from a successful PK study of a custom Accordion pill engineered to deliver a Novartis compound to entice the Swiss drugmaker into signing a licensing agreement.

Novartis said thanks, but no thanks.

For the cash-strapped Israeli drug developer, the failure to clinch the deal marks a big blow. As of the third quarter, the company has $15.7 million in cash and equivalents, which HC Wainwright analysts estimate will keep the lights on into mid-2020.

Bris­tol-My­ers shows off a low-pro­file AML con­tender it gained from Cel­gene buy­out — and they’re tak­ing it straight to the FDA

Bristol-Myers Squibb reaped an enormous pipeline with its much-criticized $64 billion megadeal to buy Celgene. And it got a few hidden gems in the deal.

One of those gems was brought out for display on Tuesday, with a late-breaker at ASH on CC-486, which is now being prepped for regulatory filings at the FDA and elsewhere.

Celgene top-lined the positive results in a maintenance setting for acute myeloid leukemia a few months ago, but at ASH investigators pulled back the curtains on the all-important data they believe will give them an advantage in the commercial wars to come.

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