Roche con­firms pa­tient death in ACE910 PhI­II he­mo­phil­ia tri­al, spurring new ques­tions about top block­buster hope­ful

Just a few months af­ter re­port­ing a slate of se­ri­ous ad­verse events for its piv­otal Phase III study of emi­cizum­ab (ACE910) for he­mo­phil­ia, Roche has raised fresh ques­tions about the safe­ty of the drug fol­low­ing the death of one of the pa­tients in the tri­al.

In a state­ment giv­en to the Eu­ro­pean Haemophil­ia As­so­ci­a­tion, Roche says that the pa­tient in their HAVEN-1 study died fol­low­ing two se­ri­ous ad­verse events.

It is our un­der­stand­ing that a pa­tient ex­pe­ri­enced a se­ri­ous rec­tal he­m­or­rhage (the first re­port­ed SAE) and re­ceived by­pass­ing agents, in­clud­ing re­peat­ed dos­es of ac­ti­vat­ed pro­throm­bin com­plex (aPCC), af­ter which the pa­tient de­vel­oped signs of Throm­bot­ic Mi­croan­giopa­thy (TMA, the sec­ond SAE). The pre­lim­i­nary as­sess­ment is that the clin­i­cal and lab­o­ra­to­ry char­ac­ter­is­tics of this case of TMA are con­sis­tent with what was ob­served in the two pre­vi­ous­ly re­port­ed cas­es; how­ev­er, our eval­u­a­tion of the avail­able in­for­ma­tion is on­go­ing.

The in­ves­ti­ga­tor con­clud­ed that the pa­tient died as a re­sult of the rec­tal he­m­or­rhage and that Roche’s drug was not re­spon­si­ble.

Daniel O’Day

The re­port, though, rais­es fresh ques­tions about the drug’s safe­ty af­ter in­ves­ti­ga­tors had to fend off per­sis­tent ques­tions about 4 spon­ta­neous­ly re­port­ed SAEs af­ter two pa­tients had throm­boem­bol­ic events and two pa­tients de­vel­oped throm­bot­ic mi­croan­giopa­thy, or TMA. That news helped briefly buoy Shire and No­vo Nordisk, which both see a big ri­val to their block­buster he­mo­phil­ia fran­chis­es in emi­cizum­ab.

Roche re­port­ed that “these events were seen with the con­comi­tant use of mul­ti­ple dos­es of a by­pass­ing agent with emi­cizum­ab while treat­ing a break­through bleed; in some cas­es the by­pass­ing agent at dos­es ex­ceed­ing the rec­om­mend­ed la­beled dos­es.”

Leerink’s Ja­son Ger­ber­ry, who’s been cheer­lead­ing for Shire’s he­mo­phil­ia fran­chise, sees this as a pos­i­tive for es­tab­lished drugs. And he trum­pet­ed grow­ing fears that ACE910 has been tied far too fre­quent­ly to se­ri­ous cas­es of TMA.

As we’ve pre­vi­ous­ly not­ed, MEDA­Corp he­mo­phil­ia spe­cial­ists gen­er­al­ly be­lieve TMA is oc­cur­ring at too high of a rate in HAVEN-1 vs. the non-ex­is­tence of TMA with stan­dard of care. While spe­cial­ists gen­er­al­ly be­lieve the TMA is an is­sue caused by the com­bi­na­tion of the two treat­ments, the root cause is not un­der­stood and thus it re­mains a pos­si­bil­i­ty that the TMA’s could be an ACE910 monother­a­py is­sue giv­en the Mab’s long half-life. In our view, ACE910 con­tin­ues to pose a risk to a por­tion of SH­PG’s FEI­BA fran­chise ($900m to­tal) giv­en the high un­met need in HA in­hibitor seg­ment, but we are of the view that ACE910 will get more mod­est trac­tion in the HA non-in­hibitor pop­u­la­tion where Shire de­rives $2.8bn (~18-19% of sales).

Long one of Roche’s top prospects, as laid out by phar­ma chief Daniel O’Day, Genen­tech re­searchers say that the drug hit the pri­ma­ry as well as all the sec­ondary end­points in their late-stage test. The big goal was a sta­tis­ti­cal­ly sig­nif­i­cant drop in the num­ber of bleeds among pa­tients with in­hibitors to fac­tor VI­II. And one of the sec­on­daries was a re­duc­tion in bleeds record­ed in an “in­tra-pa­tient com­par­i­son in peo­ple who had re­ceived pri­or by­pass­ing agent pro­phy­lax­is treat­ment.”

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

David Meline (file photo)

Mod­er­na’s new CFO took a cut in salary to jump to the mR­NA rev­o­lu­tion­ary. But then there’s the rest of the com­pen­sa­tion pack­age

David Meline took a little off the top of his salary when he jumped from the CFO post at giant Amgen to become the numbers czar at the upstart vaccines revolutionary Moderna. But the SEC filing that goes with a major hire also illustrates how it puts him in line for a fortune — provided the biotech player makes good as a promising game changer.

To be sure, there’s nothing wrong with the base salary: $600,000. Or the up-to 50% annual cash bonus — an industry standard — that comes with it. True, the 62-year-old earned $999,000 at Amgen in 2019, but it’s the stock options that really count in the current market bliss for all things biopharma. And there Meline did well.

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Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development.

President Donald Trump (left) and Moncef Slaoui, head of Operation Warp Speed (Alex Brandon, AP Images)

UP­DAT­ED: White House names fi­nal­ists for Op­er­a­tion Warp Speed — with 5 ex­pect­ed names and one no­table omis­sion

A month after word first broke of the Trump Administration’s plan to rapidly accelerate the development and production of a Covid-19 vaccine, the White House has selected the five vaccine candidates they consider most likely to succeed, The New York Times reported.

Most of the names in the plan, known as Operation Warp Speed, will come as little surprise to those who have watched the last four months of vaccine developments: Moderna, which was the first vaccine to reach humans and is now the furthest along of any US effort; J&J, which has not gone into trials but received around $500 million in funding from BARDA earlier this year; the joint AstraZeneca-Oxford venture which was granted $1.2 billion from BARDA two weeks ago; Pfizer, which has been working with the mRNA biotech BioNTech; and Merck, which just entered the race and expects to put their two vaccine candidates into humans later this year.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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Por­tion of Neil Wood­ford’s re­main­ing in­vest­ments, in­clud­ing Nanopore, sold off for $284 mil­lion

It’s been precisely one year and one day since Neil Woodford froze his once-vaunted fund, and while a global pandemic has recently shielded him from the torrent of headlines, the fallout continues.

Today, the California-based patent licensing firm Acacia Research acquired the fund’s shares for 19 healthcare and biotech companies for $284 million.  Those companies include shares for public and private companies and count some of Woodford’s most prominent bio-bets, such as Theravance Biopharma, Oxford Nanopore and Mereo Biopharma, according to Sky News, which first reported the sale. It won’t include shares for BenevelontAI, the machine learning biotech once valued at $2 billion.

Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.