Does an im­proved safe­ty pro­file strength­en Al­ler­gan's case for a wet AMD chal­lenge to Lu­cen­tis?

Al­ler­gan has chalked up some flat­ter­ing safe­ty da­ta for abic­i­par as it re­fines the eye drug’s man­u­fac­tur­ing process­es in prepa­ra­tion of an im­pend­ing BLA fil­ing. But whether or how much that mat­ters is still up for de­bate.

In an open-la­bel, sin­gle-arm study, in­ves­ti­ga­tors re­port­ed that the in­ci­dence of in­traoc­u­lar in­flam­ma­tion was 8.9% — low­er than the rate ob­served in pri­or Phase III stud­ies, which hov­ered around 15%. The MAPLE tri­al re­cruit­ed 123 age-re­lat­ed neo­vas­cu­lar mac­u­lar de­gen­er­a­tion (or wet AMD) pa­tients and ad­min­is­tered the in­jec­tion five times over 28 weeks.

David Nichol­son, Al­ler­gan

“The re­sults of this open-la­bel study en­abled us to as­sess im­prove­ments to the man­u­fac­tur­ing process for abic­i­par. The safe­ty pro­file demon­strat­ed in MAPLE gives us con­fi­dence to pro­ceed and scale up man­u­fac­tur­ing,” said David Nichol­son, chief re­search and de­vel­op­ment of­fi­cer. “We plan to sub­mit the abic­i­par BLA and con­tin­ue to pur­sue man­u­fac­tur­ing process im­prove­ments as we de­vel­op larg­er scale stud­ies in ad­di­tion­al dis­ease states, such as di­a­bet­ic mac­u­lar ede­ma.”

Any lit­tle im­prove­ment could be cru­cial as Al­ler­gan and its al­lies at Mol­e­c­u­lar Part­ners go up against the en­trenched mar­ket lead­ers, Re­gen­eron’s Eylea and No­var­tis’ Lu­cen­tis, both ap­proved for mul­ti­ple in­di­ca­tions oth­er than wet AMD, which is far less com­mon but much more se­vere than dry AMD. And the two gi­ants are each ad­vanc­ing fol­low-on ef­forts of their own.

The new in­flam­ma­tion rates, though, might still do lit­tle to change in­vestors’ skep­ti­cal views on the com­mer­cial prospect, said Umer Raf­fat of Ever­core ISI.

Raf­fat notes that se­vere in­flam­ma­tion reg­is­tered at 1.6% in the MAPLE tri­al, com­pared to 3.2% to 3.7% ob­served in pre­vi­ous Phase III stud­ies.

AGN feels strong­ly that it’s re­al­ly just the se­vere in­flam­ma­tion that mat­ters … and that it’s now at a well con­trolled rate (<2%) … and that mild in­flam­ma­tion is asymp­to­matic.

If we agree with AGN’s log­ic, there is an impt piece of da­ta that hasn’t been dis­closed about MAPLE: the rate of mod­er­ate in­flam­ma­tion. (we know mild+mod+se­vere = 8.9% … and se­vere is 1.6% … but what is mod­er­ate? if we go by Ph 3 re­sults, mod­er­ate could be half of this 8.9% … but un­clear if that ac­tu­al­ly hap­pened in MAPLE al­so).

To put it blunt­ly: “It will be a ‘show-me’ sto­ry at launch.”

An­a­lysts for SVB Leerink was even more doubt­ful, not­ing:

Re­port­ed in­ci­dence of in­traoc­u­lar in­flam­ma­tion (IOI) was 8.9% in the MAPLE study, which was low­er than pri­or Phase 3 stud­ies (>15% af­ter 1 year of treat­ment), but still sig­nif­i­cant­ly high­er than the rate ob­served in No­var­tis’ (NVS, NR) Lu­cen­tis and Re­gen­eron’s (REGN, OP) Eylea, which we think would lim­it its suc­cess to be a re­al play­er in the space.

In­vestors seem to be sit­ting this one out for now. Al­ler­gan $AGN shares are slight­ly in the red this morn­ing, dip­ping 0.33%, or $0.5, pre-mar­ket.

The duo has pre­vi­ous­ly tout­ed Phase III da­ta sug­gest­ing abic­i­par is non-in­fe­ri­or to Lu­cen­tis on both test­ed sched­ules, though the in­ci­dence of in­traoc­u­lar in­flam­ma­tion re­mained a sore point giv­en that less than 1% of the pa­tients on the ri­val drug ex­pe­ri­enced it.

Where Al­ler­gan is hop­ing to stand out is the dos­ing reg­i­men, a fixed 12-week reg­i­men that could “great­ly re­duce the treat­ment bur­den” ac­cord­ing to Cleve­land Clin­ic Cole Eye In­sti­tute’s Pe­ter Kaiser. That’s thanks to Mol­e­c­u­lar Part­ners’ DARPin tech­nol­o­gy, which it says has high­er sta­bil­i­ty and po­ten­cy than mon­o­clon­al an­ti­bod­ies.

A BLA is still slat­ed for the next two months, Al­ler­gan and Mol­e­c­u­lar Part­ners say, as pre­vi­ous­ly re­port­ed.

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.