Lit­tle Cona­tus' No­var­tis-part­nered liv­er drug suf­fers third straight de­feat, but CEO Men­to is still hold­ing out hope

Lit­tle Cona­tus’ No­var­tis-part­nered liv­er drug is one step clos­er to the scrap heap, with its third mid-stage fail­ure.

The Swiss drug­mak­er hand­ed the San Diego-based biotech $50 mil­lion up­front and an in­jec­tion of con­fi­dence in late 2016 to li­cense the drug, em­ri­c­as­an. Since then, it has flopped in a tri­fec­ta of stud­ies. An­oth­er Phase II study is ex­pect­ed to read­out lat­er this year.

Steven Men­to

The 318-pa­tient tri­al, dubbed EN­CORE-NF, was test­ing two dos­es (5 mg, 50 mg) of the drug against a place­bo in biop­sy-con­firmed NASH and liv­er fi­bro­sis pa­tients. Em­ri­c­as­an missed the pri­ma­ry end­point of im­prov­ing fi­bro­sis by ≥1 on the val­i­dat­ed Clin­i­cal Re­search Net­work (CRN) stage sys­tem, with no wors­en­ing of steato­hep­ati­tis com­pared to place­bo at week 72, the com­pa­ny said late Thurs­day.

In a sep­a­rate fil­ing, Cona­tus pro­vid­ed a lit­tle more tri­al de­tail. The re­sponse rates in the 5 mg em­ri­c­as­an, 50 mg em­ri­c­as­an and place­bo treat­ment groups were 11.2%, 12.3% and 19.0%, re­spec­tive­ly. Sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tions were ob­served in ALT (el­e­vat­ed lev­els of this en­zyme in­di­cates a liv­er in dis­tress) and Cas­pase 3/7 (en­zymes that play es­sen­tial roles in pro­grammed cell death) in the 5 mg and 50 mg em­ri­c­as­an treat­ment groups.

The com­pa­ny’s shares $CNAT more than halved pre-mar­ket on Fri­day to $1.43.

Akin to the pre­vi­ous fail­ures, Cona­tus’ CEO played it cool, sug­gest­ing the drug could still work in pa­tients with NASH, which is typ­i­cal­ly as­so­ci­at­ed with obe­si­ty and di­a­betes and is set to eclipse he­pati­tis C as the lead­ing rea­son for liv­er trans­plants by 2020.

“Al­though em­ri­c­as­an did not have the de­sired ef­fect in these ear­li­er-stage NASH fi­bro­sis pa­tients, we be­lieve its demon­strat­ed bio­mark­er ac­tiv­i­ty across a broad spec­trum of liv­er dis­ease war­rants con­tin­ued eval­u­a­tion in more ad­vanced-stage NASH cir­rho­sis pa­tients,” chief Steven Men­to said in a state­ment, adding that the com­pa­ny would await ad­di­tion­al da­ta read­outs lat­er this year be­fore de­ter­min­ing the next steps for the em­ri­c­as­an pro­gram with No­var­tis.

Stifel’s Stephen Wil­ley did not buy what Cona­tus was sell­ing. “The fail­ure…fur­ther lim­its our abil­i­ty to gen­er­ate any lin­ger­ing en­thu­si­asm for re­main­ing full year 2019 mile­stones.”

“The lim­it­ed ef­fi­ca­cy de­tails pro­vid­ed by man­age­ment ac­tu­al­ly sug­gest­ed a di­rec­tion­al detri­ment in em­ri­c­as­an-treat­ed pa­tients…the lack of any clin­i­cal con­se­quences as­so­ci­at­ed with these ben­e­fits is con­sis­tent with every oth­er em­ri­c­as­an study re­port­ed to date.”

Last April, em­ri­c­as­an failed its first Phase II tri­al, in­volv­ing liv­er trans­plant pa­tients with fi­bro­sis or cir­rho­sis. In De­cem­ber, the drug failed to im­press in a sec­ond study (dubbed EN­CORE-PH), in­volv­ing NASH cir­rho­sis pa­tients — whose liv­ers were cop­ing with the dam­age and still able to per­form im­por­tant func­tions, but were at high risk for de­com­pen­sa­tion.

Wil­ley pre­dict­ed the Phase IIb EN­CORE-LF tri­al, slat­ed for read­out in mid-2019 and in­volv­ing de­com­pen­sat­ed NASH pa­tients, is al­so doomed to fail, giv­en that the 5/25mg em­ri­c­as­an dos­es giv­en in EN­CORE-PH ac­tu­al­ly re­sult­ed in wors­en­ing of symp­toms in pa­tients with base­line de­com­pen­sat­ed cir­rho­sis.

“(T)he on­ly em­ri­c­as­an dose with­in EN­CORE-PH to sug­gest an in­cre­men­tal ben­e­fit in de­com­pen­sat­ed pa­tients was the 50mg dose – which isn’t even be­ing eval­u­at­ed in EN­CORE-LF. We al­so be­lieve EN­CORE-LF-el­i­gi­ble pa­tients rep­re­sent a very dif­fi­cult-to-treat pop­u­la­tion of pa­tients in whom the na­ture and rate of events are of­ten both dif­fi­cult to pre­dict and un­cor­re­lat­ed to sup­port­ive care ther­a­py – mak­ing the achieve­ment of a sta­tis­ti­cal win in this set­ting an even more-chal­leng­ing en­deav­or.”

NASH — char­ac­ter­ized by a buildup of ex­cess fat in the liv­er that in­duces chron­ic in­flam­ma­tion and even­tu­al­ly cul­mi­nates in scar­ring that can lead to cir­rho­sis, liv­er fail­ure, can­cer and death — is a high risk-re­ward dis­ease that has at­tract­ed a pletho­ra of drug­mak­ers big and small, and re­searchers ex­pect it will take a cock­tail of new drugs to tru­ly de­feat the dis­ease.

In­ter­cept $ICPT in Feb­ru­ary re­port­ed that a piv­otal late-stage study test­ing its OCA treat­ment hit a high­ly sta­tis­ti­cal­ly sig­nif­i­cant score on an im­prove­ment in liv­er fi­bro­sis with­out any wors­en­ing of NASH, but missed the end­point for NASH res­o­lu­tion with­out wors­en­ing of fi­bro­sis. Gilead $GILD, mean­while, ex­pe­ri­enced a ma­jor set­back af­ter its NASH drug selon­sert­ib failed its Phase III. France’s Gen­fit is ex­pect­ed to of­fer its key NASH read­out lat­er this year.

Jim Mellon [via YouTube]

Health­i­er, longer lifes­pans will be a re­al­i­ty soon­er than you think, Ju­ve­nes­cence promis­es as it clos­es $100M round

Earlier this year, an executive from Juvenescence-backed AgeX predicted the field of longevity will eventually “dwarf the dotcom boom.” Greg Bailey, the UK-based anti-aging biotech’s CEO, certainly hopes so.

On Monday, Juvenescence completed its $100 million series B round of financing. The company is backed by British billionaire Jim Mellon — who wrote his 400-page guide to investing in the field of longevity shortly after launching the company in 2017.  Bailey, who served as a board director for seven years at Medivation before Pfizer swallowed the biotech for $14 billion, is joined by Declan Doogan, an industry veteran with stints at Pfizer and Amarin.

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.

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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.

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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.

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.

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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.

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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.

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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.

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