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.

John Hood [file photo]

UP­DATE: Cel­gene and the sci­en­tist who cham­pi­oned fe­dra­tinib's rise from Sanofi's R&D grave­yard win FDA OK

Six years after Sanofi gave it up for dead, the FDA has approved the myelofibrosis drug fedratinib, now owned by Celgene.

The drug will be sold as Inrebic, and will soon land in the portfolio at Bristol-Myers Squibb, which is finalizing a deal to acquire Celgene.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,400+ biopharma pros reading Endpoints daily — and it's free.

Ab­b­Vie gets its FDA OK for JAK in­hibitor upadac­i­tinib, but don’t look for this one to hit ex­ecs’ lofty ex­pec­ta­tions

Another big drug approval came through on Friday afternoon as the FDA OK’d AbbVie’s upadacitinib — an oral JAK1 inhibitor that is hitting the rheumatoid arthritis market with a black box warning of serious malignancies, infections and thrombosis reflecting fears associated with the class.

It will be sold as Rinvoq — at a wholesale price of $59,000 a year — and will likely soon face competition from a drug that AbbVie once controlled, and spurned. Reuters reports that a 4-week supply of Humira, by comparison, is $5,174, adding up to about $67,000 a year.

UP­DAT­ED: AveX­is sci­en­tif­ic founder was axed — and No­var­tis names a new CSO in wake of an ethics scan­dal

Now at the center of a storm of controversy over its decision to keep its knowledge of manipulated data hidden from regulators during an FDA review, Novartis CEO Vas Narasimhan has found a longtime veteran in the ranks to head the scientific work underway at AveXis, where the incident occurred. And the scientific founder has hit the exit.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,400+ biopharma pros reading Endpoints daily — and it's free.

The top 10 fran­chise drugs in bio­phar­ma his­to­ry will earn a to­tal of $1.4T (tril­lion) by 2024 — what does that tell us?

Just in case you were looking for more evidence of just how important Amgen’s patent win on Enbrel is for the company and its investors, EvaluatePharma has come up with a forward-looking consensus estimate on what the list of top 10 drugs will look like in 2024.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,400+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: Sci­en­tist-CEO ac­cused of im­prop­er­ly us­ing con­fi­den­tial in­fo from uni­corn Alec­tor

The executive team at Alector $ALEC has a bone to pick with scientific co-founder Asa Abeliovich. Their latest quarterly rundown has this brief note buried inside:

On June 18, 2019, we initiated a confidential arbitration proceeding against Dr. Asa Abeliovich, our former consulting co-founder, related to alleged breaches of his consulting agreement and the improper use of our confidential information that he learned during the course of rendering services to us as our consulting Chief Scientific Officer/Chief Innovation Officer. We are in the early stage of this arbitration proceeding and are unable to assess or provide any assurances regarding its possible outcome.

There’s no explicit word in the filing on what kind of confidential info was involved, but the proceeding got started 2 days ahead of Abeliovich’s IPO.

Abeliovich, formerly a tenured associate professor at Columbia, is a top scientist in the field of neurodegeneration, which is where Alector is targeted. More recently, he’s also helped start up Prevail Therapeutics as the CEO, which raised $125 million in an IPO. And there he’s planning on working on new gene therapies that target genetically defined subpopulations of Parkinson’s disease. Followup programs target Gaucher disease, frontotemporal dementia and synucleinopathies.

But this time Abeliovich is the CEO rather than a founding scientist. And some of their pipeline overlaps with Alector’s.

Abeliovich and Prevail, though, aren’t taking this one lying down.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,400+ biopharma pros reading Endpoints daily — and it's free.

Chi­na has be­come a CEO-lev­el pri­or­i­ty for multi­na­tion­al phar­ma­ceu­ti­cal com­pa­nies: the trend and the im­pli­ca­tions

After a “hot” period of rapid growth between 2009 and 2012, and a relatively “cooler” period of slower growth from 2013 to 2015, China has once again become a top-of-mind priority for the CEOs of most large, multinational pharmaceutical companies.

At the International Pharma Forum, hosted in March in Beijing by the R&D Based Pharmaceutical Association Committee (RDPAC) and the Pharmaceutical Research and Manufacturers of America (PhRMA), no fewer than seven CEOs of major multinational pharmaceutical firms participated, including GSK, Eli Lilly, LEO Pharma, Merck KGaA, Pfizer, Sanofi and UCB. A few days earlier, the CEOs of several other large multinationals attended the China Development Forum, an annual business forum hosted by the research arm of China’s State Council. It’s hard to imagine any other country, except the US, having such drawing power at CEO level.

As dis­as­ter struck, Ab­b­Vie’s Rick Gon­za­lez swooped in on Al­ler­gan with an of­fer Brent Saun­ders couldn’t say no to

Early March was a no good, awful, terrible time for Allergan CEO Brent Saunders. His big lead drug had imploded in a Phase III disaster and activists were after his hide — or at least his chairman’s title — as the stock price continued a steady droop that had eviscerated share value for investors.

But it was a perfect time for AbbVie CEO Rick Gonzalez to pick up the phone and ask Saunders if he’d like to consider a “strategic” deal.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,400+ biopharma pros reading Endpoints daily — and it's free.

CEO Pascal Soriot via Getty Images

As­traZeneca's jug­ger­naut PARP play­er Lyn­parza scoops up an­oth­er dom­i­nant win in PhI­II as the FDA adds a 'break­through' for Calquence

AstraZeneca’s oncology R&D group under José Baselga keeps churning out hits.

Wednesday morning the pharma giant and their partners at Merck parted the curtains on a successful readout for their Phase III PAOLA-1 study, demonstrating statistically significant improvement in progression-free survival for women with ovarian cancer in a first-line maintenance setting who added their PARP Lynparza to Avastin. This is their second late-stage success in ovarian cancer, which will help stave off rivals like GSK.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,400+ biopharma pros reading Endpoints daily — and it's free.

ICER blasts FDA, PTC and Sarep­ta for high prices on DMD drugs Em­flaza, Ex­ondys 51

ICER has some strong words for PTC, Sarepta and the FDA as the US drug price watchdog concludes that as currently priced, their respective new treatments for Duchenne muscular dystrophy are decidedly not cost-effective.

The final report — which cements the conclusions of a draft issued in May — incorporates the opinion of a panel of 17 experts ICER convened in a public meeting last month. It also based its analysis of Emflaza (deflazacort) and Exondys 51 (eteplirsen) on updated annual costs of $81,400 and over $1 million, respectively, after citing “incorrect” lower numbers in the initial calculations.