Fa­tal sep­sis at­tacks blight Acor­da’s PhI­II, trig­ger­ing new safe­ty mea­sures and tor­pe­do­ing shares

Af­ter track­ing 7 cas­es of sep­sis — with 5 deaths — in stud­ies of its late-stage Parkin­son’s drug tozadenant, Acor­da is in­creas­ing pa­tient sur­veil­lance while paus­ing en­roll­ment in its long-term safe­ty stud­ies to get a han­dle on the is­sue.

Acor­da’s shares plunged 40% on the news.

The safe­ty is­sue arose af­ter re­searchers be­came aware of the cas­es of agran­u­lo­cy­to­sis, wip­ing out the white blood cells need­ed to fight off an in­fec­tion. Now they say they will check those cell counts on a week­ly ba­sis as they study the po­ten­tial drug prob­lem with the FDA and the mon­i­tor­ing com­mit­tee.

Ron Co­hen

Acor­da CEO Ron Co­hen says they still ex­pect to re­port out Phase III safe­ty and ef­fi­ca­cy da­ta in Q1 com­ing up, but any threat to its num­ber two de­vel­op­ment pro­gram — be­hind CVT-301 — is like­ly to rat­tle its back­ers.

Leerink’s Paul Mat­teis says the sur­pris­ing news of a ma­jor safe­ty is­sue at Acor­da leaves the drug un­der a cloud.

The need for fre­quent white blood cell mon­i­tor­ing is not un­heard of for ap­proved neu­rol­o­gy prod­ucts: agran­u­lo­cy­to­sis risk is a known lim­i­ta­tion for cloza­p­ine, an ap­proved, and very ef­fec­tive atyp­i­cal an­tipsy­chot­ic. But the risk/ben­e­fit for Toz, in the con­text of an ap­par­ent mor­tal­i­ty sig­nal – and what is al­ready a crowd­ed cat­e­go­ry – is now sig­nif­i­cant­ly com­pro­mised, giv­en that the drug is not dis­ease-mod­i­fy­ing and will be tar­get­ed to­ward an al­ready frag­ile el­der­ly pop­u­la­tion.

Then, lat­er on Wednes­day, Mat­teis vir­tu­al­ly wrote it off as a los­er.

We are now very con­cerned re­gard­ing the ap­prov­abil­i­ty of Toz – even if it does work – giv­en its po­si­tion­ing as a symp­to­matic ther­a­py with a mod­er­ate lev­el of ben­e­fit. We have sig­nif­i­cant ques­tions re­gard­ing the com­mer­cial vi­a­bil­i­ty of a new symp­to­matic Parkin­son’s ther­a­py with such sig­nif­i­cant safe­ty risks.

Acor­da swooped in to buy Fin­land’s Bi­otie in ear­ly 2016 for $363 mil­lion in cash to bag the Phase III Parkin­son’s drug and add a bad­ly need­ed late-stage drug to the pipeline. Tozadenant is an oral adeno­sine A2a re­cep­tor an­tag­o­nist that’s reg­is­tered proof of con­cept da­ta for re­duc­ing “off” times among Parkin­son’s pa­tients tak­ing the stan­dard lev­odopa/car­bidopa rem­e­dy.

There’s lit­tle mar­gin for er­ror at Acor­da.

With its patents on the com­pa­ny’s cash cow Ampyra un­der at­tack, pos­si­bly open­ing the road to a gener­ic ri­val next sum­mer, the biotech has had to re-file its ap­pli­ca­tion for CVT-301. The FDA had is­sued a refuse-to-file the ap­pli­ca­tion for the drug, de­lay­ing a ther­a­py which will be need­ed to res­cue the com­pa­ny from gener­ic com­pe­ti­tion for Ampyra.

The biotech, mean­while, has moved to re­struc­ture, block a po­ten­tial hos­tile takeover at­tempt and de­flect crit­i­cism for leav­ing it­self vul­ner­a­ble to the cri­sis it’s in. If its safe­ty is­sue with tozadenant spins out of con­trol, Acor­da’s ex­ec­u­tive team will be un­der twice as much pres­sure to per­form on CVT-301.

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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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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Hal Barron. GSK

GSK's Hal Bar­ron her­alds their sec­ond pos­i­tive piv­otal for cru­cial an­ti-BC­MA ther­a­py, point­ing to a push for quick OKs in a crowd­ed field

Hal Barron has his second positive round of Phase III data in hand for his anti-BCMA antibody drug conjugate belantamab mafodotin (GSK2857916). And GSK’s research chief says the data paves the way for their drive in search of an FDA approval for treating multiple myeloma.

It’s hard to overestimate the importance of this drug for GSK, a cornerstone of Barron’s campaign to make a dramatic impact on the oncology market and provide some long-lost excitement for the pharma giant’s pipeline. They’re putting this BCMA program at the front of that charge — looking to lead a host of rivals all aimed at the same target.

We don’t know what the data are yet, but DREAMM-2 falls on the heels of a promising set of data delivered 5 months ago for DREAMM-1. There investigators noted that complete responses among treatment-resistant patients rose to 15% in the extra year’s worth of data to look over, with a median progression-free survival rate of 12 months, up from 7.9 months reported earlier. The median duration of response was 14.3 months.

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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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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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Why would Am­gen want to buy Alex­ion? An­a­lysts call hot­ly ru­mored takeover un­like­ly, but seize the mo­ment

A rumor that Amgen is closing in on buyout deal for Alexion has sparked a guessing game on just what kind of M&A strategy Amgen is pursuing and how much Alexion is worth.

Mizuho analyst Salim Syed first lent credence to the report out of the Spanish news outlet Intereconomía, which said Amgen is bidding as much as $200 per share. While the source may be questionable, “the concept of this happening doesn’t sound too crazy to me,” he wrote.

FDA asks why No­var­tis took two months to launch for­mal in­ter­nal probe, af­ter AveX­is flagged da­ta ma­nip­u­la­tion

And the plot thickens. Novartis $NVS officials are reportedly now scrambling to explain to the FDA why it took them two months to open an internal investigation into data discrepancies for their $2.1 million gene-therapy for spinal muscular dystrophy — the world’s most expensive drug.

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Build­ing on suc­cess­ful PD-1 pact, Eli Lil­ly li­cens­es di­a­betes drug to Chi­nese part­ners at In­novent

Eli Lilly is expanding its partnership with China’s Innovent in a deal involving a diabetes drug sitting in its Phase I reserves.

The two companies had jointly developed one of China’s first homegrown PD-1 agents, scoring an approval for Tyvyt (sintilimab) late last year for relapsed/refractory classical Hodgkin’s lymphoma. This time around, Lilly is out-licensing a piece of its diabetes pipeline, a leading franchise that has historically produced the top-selling Trulicity and Humalog.

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.