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.

Nick Leschly via Getty

UP­DAT­ED: Blue­bird shares sink as an­a­lysts puz­zle out $1.8M stick­er shock and an un­ex­pect­ed de­lay

Blue­bird bio $BLUE has un­veiled its price for the new­ly ap­proved gene ther­a­py Zyn­te­glo (Lenti­Glo­bin), which came as a big sur­prise. And it wasn’t the on­ly un­ex­pect­ed twist in to­day’s sto­ry.

With some an­a­lysts bet­ting on a $900,000 price for the β-tha­lassemia treat­ment in Eu­rope, where reg­u­la­tors pro­vid­ed a con­di­tion­al ear­ly OK, blue­bird CEO Nick Leschly said Fri­day morn­ing that the pa­tients who are suc­cess­ful­ly treat­ed with their drug over 5 years will be charged twice that — $1.8 mil­lion — on the con­ti­nent. That makes this drug the sec­ond most ex­pen­sive ther­a­py on the plan­et, just be­hind No­var­tis’ new­ly ap­proved Zol­gens­ma at $2.1 mil­lion, with an­a­lysts still wait­ing to see what kind of pre­mi­um can be had in the US.


Glob­al Blood Ther­a­peu­tics poised to sub­mit ap­pli­ca­tion for ac­cel­er­at­ed ap­proval, with new piv­otal da­ta on its sick­le cell dis­ease drug

Global Blood Therapeutics is set to submit an application for accelerated approval in the second-half of this year, after unveiling fresh data from a late-stage trial that showed just over half the patients given the highest dose of its experimental sickle cell disease drug experienced a statistically significant improvement in oxygen-wielding hemoglobin, meeting the study's main goal.

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News­mak­ers at #EHA19: Re­gen­eron, Ar­Qule track progress on re­sponse rates

Re­gen­eron’s close­ly-watched bis­pe­cif­ic con­tin­ues to ring up high re­sponse rates

Re­gen­eron’s high-pro­file bis­pe­cif­ic REGN1979 is back in the spot­light at the Eu­ro­pean Hema­tol­ogy As­so­ci­a­tion sci­en­tif­ic con­fab. And while the stel­lar num­bers we saw at ASH have erod­ed some­what as more blood can­cer pa­tients are eval­u­at­ed, the re­sponse rates for this CD3/CD20 drug re­main high.

A to­tal of 13 out of 14 fol­lic­u­lar lym­phomas re­spond­ed to the drug, a 93% ORR, down from 100% at the last read­out. In 10 out of 14, there was a com­plete re­sponse. In dif­fuse large B-cell lym­phoma the re­sponse rate was 57% among pa­tients treat­ed at the 80 mg to 160 mg dose range. They were all com­plete re­spons­es. And 2 of these Cars were for pa­tients who had failed CAR-T ther­a­py.

Search­ing for the next block­buster to fol­low Darza­lex, J&J finds a $150M an­ti-CD38 drug from part­ner Gen­mab

Now that J&J and Genmab have thrust Darzalex onto the regulatory orbit for first-line use in multiple myeloma, the partners are lining up a deal for a next-gen follow-on to the leading CD38 drug.

Janssen — J&J’s biotech unit — has its eyes on HexaBody-CD38, a preclinical compound generated on Genmab’s tech platform designed to make drugs more potent via hexamerization.

Genmab is footing the bill on studies in multiple myeloma and diffuse large B-cell lymphoma; once it completes clinical proof of concept, Janssen has the option to license the drug for a $150 million exercise fee. There’s also $125 million worth of milestones in play.

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Gene ther­a­pies seize the top of the list of the most ex­pen­sive drugs on the plan­et — and that trend has just be­gun

Anyone looking for a few simple reasons why the gene therapy field has caught fire with the pharma giants need only look at the new list of the 10 most expensive therapies from GoodRx.

Two recently approved gene therapies sit atop this list, with Novartis’ Zolgensma crowned the king of the priciest drugs at $2.1 million. Right below is Luxturna, the $850,000 pioneer from Spark, which Roche is pushing hard to acquire as it adds a gene therapy group to the global mix.

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Savara shares are crushed as PhI­II tri­al flunks pri­ma­ry, key sec­on­daries — but they can’t stop be­liev­ing

In­vestors are in no mood to hear biotechs tout the suc­cess of a “key” sec­ondary end­point when the piv­otal Phase III flunks the pri­ma­ry goal. Just ask Savara. 

The Texas biotech $SVRA went look­ing for a sil­ver lin­ing as com­pa­ny ex­ecs blunt­ly con­ced­ed that Mol­gradex, an in­haled for­mu­la­tion of re­com­bi­nant hu­man gran­u­lo­cyte-macrophage colony-stim­u­lat­ing fac­tor (GM-CSF), failed to spur sig­nif­i­cant­ly im­proved treat­ment out­comes for pa­tients with a rare res­pi­ra­to­ry dis­ease called au­toim­mune pul­monary alve­o­lar pro­teinosis, or aPAP.

As an­oth­er an­tibi­otics biotech sinks in­to a cri­sis, warn­ings of a sec­tor ‘col­lapse’

Another antibiotics company is scrambling to survive today, forcing the company’s founding CEO to exit in a reorganization that eliminates its research capabilities as the survivors look to improve on minuscule sales of their newly approved treatment. And the news — on top of an alarming series of failures — spurred at least one figure in the field to warn of a looming collapse of the antimicrobial resistance research field.

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'We kept at it': Jef­frey Blue­stone plots late-stage come­back af­ter teplizum­ab shown to de­lay type 1 di­a­betes

Late-stage da­ta pre­sent­ed at the Amer­i­can Di­a­betes As­so­ci­a­tion an­nu­al meet­ing in 2010 pushed Eli Lil­ly to put a crimp on teplizum­ab as the phar­ma gi­ant found it un­able to re­set the clock on new­ly di­ag­nosed type 1 di­a­betes. At the same con­fer­ence but in dif­fer­ent hands nine years lat­er, the drug is mak­ing a crit­i­cal come­back by scor­ing suc­cess in an­oth­er niche: de­lay­ing the on­set of the dis­ease.

In a Phase II tri­al with 76 high-risk in­di­vid­u­als — rel­a­tives of pa­tients with type 1 di­a­betes who have di­a­betes-re­lat­ed au­toan­ti­bod­ies in their bod­ies — teplizum­ab al­most dou­bled the me­di­an time of di­ag­no­sis com­pared to place­bo (48.4 months ver­sus 24.4 months). The haz­ard ra­tio for di­ag­no­sis was 0.41 (p=0.006).

Bain’s biotech team has cre­at­ed a $1B-plus fund — with an eye to more Big Phar­ma spin­outs

One of the biggest investors to burst onto the biotech scene in recent years has re-upped with more than a billion dollars flowing into its second fund. And this next wave of bets will likely include more of the Big Pharma spinouts that highlighted their first 3 years in action.

Adam Koppel and Jeff Schwartz got the new life sciences fund at Bain Capital into gear in the spring of 2016, as they were putting together a $720 million fund with $600 million flowing in from external investors and the rest drawn from the Bain side of the equation. This time the external investors chipped in $900 million, with Bain coming in for roughly $180 million more.

They’re not done with Fund I, with plans to add a couple more deals to the 15 they’ve already posted. And once again, they’re estimating another 15 to 20 investments over a 3- to 5-year time horizon for Fund II.

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