Au­rinia eye drug falls short in im­prov­ing tol­er­a­bil­i­ty ver­sus Resta­sis, but beats on ef­fi­ca­cy

Al­ler­gan’s best-sell­ing dry eye drug Resta­sis was de­vel­oped af­ter the im­muno­sup­pres­sant was orig­i­nal­ly shown to en­hance tear pro­duc­tion in dogs. Sim­i­lar­ly, Cana­da’s Au­rinia Phar­ma $AUPH found its ex­per­i­men­tal treat­ment was do­ing well in ca­nine stud­ies, prompt­ing their eval­u­a­tion of the drug — vo­closporin opthalmic so­lu­tion (VOS) — in hu­mans. And now in a Phase II study com­par­ing VOS to Resta­sis, VOS failed the pri­ma­ry end­point of beat­ing the block­buster drug’s tol­er­a­bil­i­ty score, but did demon­strate a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment on sec­ondary end­points eval­u­at­ing ef­fi­ca­cy.

Richard Glick­man

Resta­sis is a pre­scrip­tion eye drop that con­tains cy­closporine, which tar­gets a ubiq­ui­tous en­zyme called cal­cineurin found in cell cy­to­plasm. It takes about 3-6 months for the drug to work, and about 17% of pa­tients dis­con­tin­ue us­ing the drug due to both­er­some side-ef­fects such as burn­ing and itch­ing. Still, large­ly due to a per­sis­tent mar­ket­ing ef­fort the drug has gen­er­at­ed bil­lions of dol­lars in rev­enue for Al­ler­gan since its 2003 ap­proval. The com­pa­ny has used a cre­ative so­lu­tion to en­hance the patent life of its sec­ond-biggest sell­er, by trans­fer­ring the drug’s patents to a Na­tive Amer­i­can tribe to stave off com­pe­ti­tion, but that strat­e­gy has run in­to le­gal and PR trou­ble. Al­ler­gan and their Mo­hawk al­lies are now tak­ing the case to the Supreme Court — pro­vid­ed the jus­tices agree to hear it.

Au­rinia’s VOS has a long way to go be­fore it can win ap­proval. But if it does, it will com­pete with cheap Resta­sis gener­ics — rais­ing the bar sub­stan­tial­ly on any mar­ket show­down.

VOS is a “next-gen” cy­closporine in­hibitor sus­pend­ed in a na­nomi­cel­lar so­lu­tion, de­signed to be four times as po­tent as cy­closporine.

“VOS is a de­riv­a­tive of cy­closporin…it binds dif­fer­ent­ly, and is more po­tent, there­fore we ac­tu­al­ly need less drug. In this case, we de­cid­ed to use more of the drug,” Au­rinia CEO Richard Glick­man ex­plained in an in­ter­view pre­ced­ing the re­sults. “When you treat pa­tients with an eye drop, they blink. When they blink they ac­tu­al­ly wipe off a great deal of that drug — so ba­si­cal­ly we are de­liv­er­ing more drug, so even if they blink and wipe it off — the idea is that more drug pen­e­trates the eye.”

VOS was test­ed against Resta­sis in a 100-pa­tient 28-day study. The main goal of the study, to im­prove tol­er­a­bil­i­ty as mea­sured by “drop dis­com­fort” one minute fol­low­ing drug ad­min­is­tra­tion, was not met, with both arms re­port­ing sim­i­lar rates.

“We didn’t see a sig­nif­i­cant dif­fer­ence cause there was very lit­tle dis­com­fort at all on the ad­min­is­tra­tion of drops…and we can’t re­al­ly be sure why,” Au­rinia chief med­ical of­fi­cer Neil Solomons told End­points News. The com­pa­ny’s shares were down about 5% in morn­ing trad­ing.

Neil Solomons

Al­ler­gan orig­i­nal­ly sought US ap­proval for Resta­sis in 1999, but that ap­pli­ca­tion failed on the ba­sis of in­con­sis­tent da­ta from two late-stage tri­als, fol­low­ing which the drug­mak­er re­an­a­lyzed its da­ta and amend­ed its ap­pli­ca­tion four times. The FDA ul­ti­mate­ly sanc­tioned the drug’s ap­proval in 2003, based on a sur­ro­gate sign — the Schirmer re­sponse — a test used to mea­sure tear pro­duc­tion. Since then oth­er drugs for dry eye have been ap­proved by the FDA, in­clud­ing Sun Phar­ma’s Ce­qua and Shire’s Xi­idra, which both take up to 12 weeks to take ef­fect.

Dry eye, which typ­i­cal­ly oc­curs with age, is char­ac­ter­ized by the di­min­ished quan­ti­ty and/or qual­i­ty of tears, which fail to keep the sur­face of the eye ad­e­quate­ly lu­bri­cat­ed. It is es­ti­mat­ed to im­pact more than 16 mil­lion in the Unit­ed States.

In Au­rinia’s head-to-head tri­al, VOS eclipsed Resta­sis on two mea­sures of ef­fi­ca­cy: The Schirmer test (STT) and Flu­o­res­cein Corneal Stain­ing/FCS (a test used mea­sure struc­tur­al dam­age to the cornea). At week four, VOS showed rapid and sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ments (STT: p=.0051; FCS: p=.0003) over Resta­sis. Da­ta showed that VOS be­gan to con­fer a sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tion in FCS ver­sus Resta­sis by week 2, the com­pa­ny added.

“The ef­fi­ca­cy end­points clear­ly sig­nal that VOS has the po­ten­tial to have a more rapid on­set than Resta­sis,” Can­tor Fitzger­ald’s El­e­mer Piros wrote in a note.

“If you ac­tu­al­ly look at the da­ta across the board, it’s quite con­sis­tent and re­mark­able — we didn’t need to slice and dice the da­ta, or cre­ate a sub­set of pa­tients — we just picked the wrong pri­ma­ry end­point,” Glick­man said. “We’re ac­tu­al­ly a lot sur­prised by the mag­ni­tude of the re­sponse ac­tu­al­ly, be­cause when we pow­ered the study we thought it would be eas­i­er to pick the low hang­ing fruit, which was…drop dis­com­fort. Drop dis­com­fort turns out to be tougher than we thought in the sense that both drugs in our study ac­tu­al­ly didn’t both­er pa­tients a whole lot.”

Leerink’s Joseph Schwartz sug­gest­ed that the sur­pris­ing ef­fi­ca­cy da­ta over­shad­owed the miss on tol­er­a­bil­i­ty.

“We think the on par tol­er­a­bil­i­ty of VOS de­spite a ~16x high­er con­cen­tra­tion of drug de­liv­ered il­lus­trates that there could be room for im­prove­ment via eval­u­at­ing low­er dos­es in fu­ture tri­als, a con­cept man­age­ment dis­closed as a po­ten­tial strat­e­gy in their next study. Sur­pris­ing­ly, giv­en the study’s pow­er­ing as­sump­tions, treat­ment with VOS sig­nif­i­cant­ly im­proved key ef­fi­ca­cy out­comes, which we think are more rel­e­vant for reg­is­tra­tional stud­ies and mar­ket up­take,” Schwartz wrote in a note.

Au­rinia is con­vinced the dataset is com­pelling enough to plan a larg­er Phase II/III tri­al.

If all goes well go­ing for­ward, the British Co­lum­bia-based com­pa­ny is hop­ing a drug­mak­er with deep­er pock­ets comes along to help out on the com­mer­cial side. Mean­while, the com­pa­ny’s main fo­cus is its lu­pus pro­gram, for which late-stage da­ta are ex­pect­ed by the end of 2019.

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.

Neil Woodford, Woodford Investment Management via YouTube

Un­der siege, in­vest­ment man­ag­er Wood­ford faces an­oth­er in­vest­ment shock

Em­bat­tled UK fund man­ag­er Neil Wood­ford — who has con­tro­ver­sial­ly blocked in­vestors from pulling out from his flag­ship fund to stem the blood­let­ting, af­ter a slew of dis­ap­point­ed in­vestors fled fol­low­ing a se­ries of sour bets — is now pay­ing the price for his ac­tions via an in­vestor ex­o­dus on an­oth­er fund.

Har­g­reaves Lans­down, which has in the past sold and pro­mot­ed the Wood­ford funds via its re­tail in­vest­ment plat­form, has re­port­ed­ly with­drawn £45 mil­lion — its en­tire po­si­tion — from the in­vest­ment man­ag­er’s In­come Fo­cus Fund.

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).