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.”

UP­DAT­ED: Roche bags 'break­through' an­ti-fi­bro­sis drug in $1.4B biotech buy­out deal

Roche is snapping up a “breakthrough” anti-fibrotic drug in a $1.4 billion buyout.

The pharma giant announced Friday that it is acquiring Promedior, primarily to get its hands on PRM-151, a recombinant form of human pentraxin-2 (PTX-2) protein that has nailed down mid-stage clinical data on idiopathic pulmonary fibrosis and demonstrating its potential for a range of fibrotic conditions.

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Amarin emerges from an ex­pert pan­el re­view with a clear en­dorse­ment for Vas­cepa and high odds of suc­cess when the FDA weighs in for­mal­ly

Several FDA experts who gathered Thursday to consider the landmark approval of Vascepa to reduce cardio events in an at-risk population voiced their unease about various aspects of the efficacy and safety data, or ultimately the population it should be used to treat. But the overwhelming belief that the data pointed to the drug’s benefit and clearly outweighed risks carried the day for Amarin.

The panel voted unanimously (16 to 0) to support the company’s positive data presentation — backing an OK for expanding the label to include reducing cardio risk. The vote points Amarin $AMRN down a short path to a formal decision by the FDA, with the odds heavily in its favor. Chances are the rest of the questions about the future of this drug will be hashed out in the label’s small print.

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Federal Trade Commission commissioner Rohit Chopra testifies on Capitol Hill (AP Photo/Susan Walsh)

FTC clears Bris­tol-My­ers’ $74B deal to buy Cel­gene — but Dems sig­nal a po­ten­tial hard shift against Big Phar­ma M&A

Bristol-Myers Squibb’s record $74 billion takeover of Celgene is a done deal. And it will all be over — except for the lingering complaints from die-hard Celgene investors — on Wednesday.

Like much else that’s going on in Washington these days, the vote among the 5 FTC commissioners split along party lines, with the 3 Republicans voting to clear the way and the 2 Democrats steamed over what they see as a major M&A move that will lessen competition and innovation. And that split has big implications for the M&A side of the business if the Dems take the White House in 2020.

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No­var­tis scores its lat­est FDA OK — this time for a new sick­le cell dis­ease drug picked up in a $665M deal

Novartis’ decision to buy Oklahoma-based biotech Selexys 3 years ago for up to $665 million has paid off with an FDA approval today.

Blessed with the FDA’s breakthrough drug designation for a speedy review, the pharma giant has pinned down an approval for crizanlizumab, a new therapy designed to reduce the frequency of painful incidents of vaso-occlusive crises among sickle cell disease patients 16 or older.

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No­var­tis spin­out’s first an­ti-ag­ing PhI­II is a flop, so now they’ll turn to Parkin­son’s chal­lenge as shares wilt

Novartis spinout resTORbio is grappling with the collapse of its lead clinical program this morning — an anti-aging R&D failure that will badly damage their rep in the field.

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BeiGene CEO John Oyler at an Endpoints event in Shanghai, October 2018 (Credit: Endpoints News/PharmCube)

UP­DAT­ED: In a first, FDA green-lights use of a Chi­nese built can­cer ther­a­py — and more are com­ing

Weeks after Amgen took a $2.7 billion stake in BeiGene, the Beijing-based biotech has secured its first-ever FDA approval for zanubrutinib, a BTK inhibitor, months ahead of schedule.

BeiGene’s drug, branded as Brukinsa, has secured accelerated approval for adult patients with mantle cell lymphoma (MCL) — a typically aggressive, rare, form of blood cancer — who have received at least one prior therapy.

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What does $62B buy you these days? A lot, says Take­da ex­ecs as the phar­ma play­er promis­es a block­buster R&D fu­ture

First comes the $62 billion buyout. Then comes the asset auction and reorganization to pay down debt. Now comes the detailed pledge of a bigger, brighter future in drug development.

That’s where Takeda finds itself on R&D day today, about 11 months after closing on their Shire acquisition. R&D chief Andy Plump is joining CEO Christophe Weber and other top members of the team to outline a new set of priorities in the greatly expanded pipeline at Takeda, which has jumped into the top ranks of the world’s pharma giants in the wake of the Shire deal.

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GSK's asth­ma bi­o­log­ic Nu­cala scores in rare blood dis­or­der study

GlaxoSmithKline’s asthma drug Nucala, which received a resounding FDA rejection for use in chronic obstructive pulmonary disease (COPD) last year, has shown promise in a rare blood disorder.

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Mer­ck buys a fledg­ling neu­rode­gen­er­a­tive biotech spawned by an old GSK dis­cov­ery al­liance. What’s up with that?

Avalon Ventures chief Jay Lichter has a well-known yen for drug development programs picked up in academia. And what he found in Haoxing Xu’s lab at the University of Michigan pricked his interest enough to launch one of his umbrella biotechs in San Diego.

Xu’s work laid the foundation for Avalon to launch Calporta, which has been working on finding small molecule agonists of TRPML1 (transient receptor potential cation channel, mucolipin subfamily, member 1) for lysosomal storage disorders. And that pathway, they believe, points to new approaches on major market neurodegenerative diseases like Parkinson’s, ALS and Alzheimer’s.

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