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.”

Take­da swoops in to buy lit­tle biotech part­ner and its celi­ac drug poised to 'change stan­dard of care'

Having spent three years carefully grooming PvP Biologics and its drug for celiac disease, Takeda is happy enough with the proof-of-concept data to buy it all.

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Grow­ing ac­cep­tance of ac­cel­er­at­ed path­ways for nov­el treat­ments: but does reg­u­la­to­ry ap­proval lead to com­mer­cial suc­cess?

By Mwango Kashoki, MD, MPH, Vice President-Technical, and Richard Macaulay, Senior Director, of Parexel Regulatory & Access

In recent years, we’ve seen a significant uptake in the use of regulatory options by companies looking to accelerate the journey of life-saving drugs to market. In 2018, 73% of the novel drugs approved by the U.S. Federal Drug Administration (FDA) were designated under one or more expedited development program categories (Fast Track, Breakthrough Therapy, Priority Review, and Accelerated Approval).ᶦ

Andre Kalil, AP Images

A 9/11-era Om­a­ha fa­cil­i­ty, an old Ebo­la drug, and the ubiq­ui­tous Dr. Fau­ci: In­side the first US nov­el coro­n­avirus tri­al

The first 11 coronavirus patients who arrived in Omaha last week, airlifted across the globe after two weeks quarantined on a cruise ship, showed only minor symptoms or none at all. And then one of them — or one of the couple of Americans who arrived later — got worse. He developed pneumonia, a life-threatening complication for coronavirus patients.

In a biocontainment room at the University of Nebraska Medical Center on Friday, doctors infused him with an experimental Gilead drug once developed for Ebola, called remdesivir. Or they gave him a placebo. For the first time in the US, neither he nor the doctors knew.

The first US novel coronavirus trial was underway and with it, a mad dash for an answer. Sponsored by the NIH, the study marked a critical point in the epidemic. Since the start of the outbreak, the agency had helped lead a global effort to contain the virus. Now, as it spread worldwide and the CDC issued warnings the US could see a major internal outbreak, they were looking at home.

“We don’t have too much time,” Andre Kalil, the trial’s lead investigator, told Endpoints News. “Everything’s moving really fast.”

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Dan O'Day (AP Images)

A name emerges out of the Gilead M&A ru­mor mill, and it’s a can­cer biotech

After months of questions and speculation about when and if Gilead will make a major acquisitions, a name has emerged.

The California-based drugmaker has approached Forty Seven Inc, a cancer biotech, with a takeover offer, Bloomberg News reports. With Forty Seven’s market cap at $2.3 billion, an acquisition would likely be Gilead’s largest since they acquired Kite Pharma for $11.9 billion in 2017.

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Biogen head of R&D Al Sandrock, Sangamo CEO Sandy Macrae

UP­DAT­ED: Bio­gen makes an­oth­er bold Alzheimer’s bet, drop­ping $350M up­front to part­ner with genome-edit­ing fo­cused Sang­amo

While the fate of Biogen’s resurrected Alzheimer’s drug aducanumab remains uncertain, the Cambridge, MA-based drugmaker is joining forces with genome editing company Sangamo Therapeutics to develop therapies for neurological conditions.

Sangamo is set to receive a meaty $350 million upfront in cash and stock and is eligible to receive up to $2.37 billion in milestone payments, in addition to royalties. In return, Biogen gets the rights to two Sangamo preclinical compounds: ST-501 (for use in tauopathies including Alzheimer’s disease) and ST-502 (for synucleinopathies including Parkinson’s disease).

“The partnership represents a lower-cost way to expand its work in neurologic disease,” Credit Suisse’s Evan Seigerman said in a note, referring to Biogen.

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Spark los­es an­oth­er top ex­ec in the wake of $4.3B takeover by Roche — re­port

Days after bidding farewell to co-founder Kathy High, Spark Therapeutics — now operating under Roche — has one more opening on its C-suite.

Kathy Reape

Kathy Reape, who joined the Philadelphia-based biotech in 2016 as head of clinical R&D and became chief medical officer in 2018, is reportedly set to leave.

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'The head­lines are the head­lines, but': Bio­Marin talks up po­ten­tial sav­ings as he­mo­phil­ia gene ther­a­py launch looms

BioMarin execs are still staying tight-lipped about their pricing plans for what is poised to be the world’s first hemophilia gene therapy. But as the company enters the final regulatory stretch and approaches a potential launch this summer, they are also dropping more hints to get investors ready.

First thing to know: They really, really don’t expect an advisory committee to be convened for valrox, which is under priority review, to pop up before its PDUFA date on August 21.

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Vlad Coric (Photo Credit: Andrew Venditti)

Bio­haven scores CGRP OK for acute mi­graine — can the com­mer­cial team catch up with Al­ler­gan on its de­but?

Seven years after spinning out of Yale, Biohaven has entered the ranks of commercial-stage biotechs.

The FDA handed down an OK for its CGRP drug, rimegepant, as an acute treatment. Dubbed Nurtec, the orally dissolving pill will join Allergan’s (soon to be AbbVie’s) Ubrelvy and Lilly’s Reyvow on the market amid a new wave of migraine therapies reshaping the disease space.

In a pivotal Phase III trial, Nurtec hit the co-primary endpoints on pain freedom and freedom from most bothersome symptoms at two hours post dose, proving superior to placebo.

An­oth­er hic­cup for GW Phar­ma's seizure drug ri­val, as Zo­genix dis­clos­es FDA re­view de­lay

Zogenix has had a troubling 2020 so far. Earlier this month, its experimental seizure drug met the main goal in a pivotal study in patients with Lennox-Gastaut Syndrome, but the company saw its shares plummet after the magnitude of the therapy’s effect fell short of Wall Street expectations. On Thursday, the drug developer said that the FDA had extended the review of the drug in patients with Dravet syndrome by three months.