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.

RWE chal­lenges for to­day's bio­phar­ma

The rapid development of technology — and the resulting avalanche of data — are catalysts for significant change in the biopharmaceutical industry. This translates into urgent pressures for today’s biopharma, including a need to quickly and affordably develop products with proven therapeutic efficacy and value. This urgency is expedited by the growth of value-based contracting, where access to reimbursement and profit depends on these abilities.

UP­DAT­ED: In a stun­ning turn­around, Bio­gen says that ad­u­canum­ab does work for Alzheimer's — but da­ta min­ing in­cites con­tro­ver­sy and ques­tions

Biogen has confounded the biotech world one more time.

In a stunning about-face, the company and its partners at Eisai say that a new analysis of a larger dataset on aducanumab has restored its faith in the drug as a game-changer for Alzheimer’s and, after talking it over with the FDA, they’ll now be filing for an approval of a drug that had been given up for dead.

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As shares suf­fer from a lin­ger­ing slump, a bruised Alk­er­mes slash­es 160 jobs in R&D re­struc­tur­ing

With its share price in a deep slump after suffering through a regulatory debacle over their depression drug ALKS 5461, Alkermes CEO Richard Pops is taking the ax to its R&D organization in a restructuring aimed at cutting costs ahead of its next attempt at a rollout in a tough field.

Richard Pops, Endpoints via Youtube

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Acor­da's Ron Co­hen brings the ax back out as new drug sales on­ly trick­le in while cash cow is led to the slaugh­ter

With its new drug earning meager sums and its one-time cash cow reduced to a bony shadow of its former self, Acorda Therapeutics today is rolling out a new restructuring aimed at slashing the staff and cutting costs to get through the hard times ahead.

The biotech is chopping a quarter of its staff today, carving back R&D as well as SG&A expenses. And CEO Ron Cohen is cutting deep.

Under the new austerity budget, Acorda’s R&D expenses for the full year 2019 are expected to be $55 – $60 million, reduced from $70 – $80 million. SG&A expenses for the full year 2019 are expected to be $185 – $190 million, reduced from $200 – $210 million. R&D expenses for the full year 2020 are expected to be $20 – $25 million and SG&A
expenses for the full year 2020 are expected to be $160 – $165 million.

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RAPT Ther­a­peu­tics re­turns to Wall Street to re­vive IPO bid

On May 24, FLX Bio, a small cancer and inflammation biotech with backing from GV, changed its name to RAPT Therapeutics and filed confidentially for an IPO. On July 5th, they filed to raise up to $86 million. On July 22, they announced the IPO with a $75 million goal.  And on August 1, they abruptly and without explanation called it all off.

Now, without explanation, they’re reviving the bid, filing again for a $75 million IPO, this time with a new bookrunner and a new drug candidate in the clinic. The terms will be the same: 5 million shares at $14-$16 per share. It would give them a diluted market value of $351 million.

EY vet set to re­place re­tir­ing Am­gen CFO Meline

Ahead of its third-quarter results next week, Amgen on Tuesday disclosed the planned retirement of David Meline, who has served as the company’s chief financial officer since 2014.

Meline will be replaced by Ernst & Young vet, Peter Griffith, as CFO come January 1, 2020 — but until then Griffith will serve as executive vice president, finance.

“Over the last 5 years at Amgen, Meline instituted many major changes that led to operational efficiencies and margin expansion while successfully returning cash to shareholders. Now that Amgen is on solid footing, it was a good time to step away,” Cowen’s Yaron Werber wrote in a note. “We do not anticipate any major changes to strategy or operations immediately due to this transition as Amgen is on solid footing.”

Eli Lil­ly’s USA, di­a­betes chief En­rique Con­ter­no is head­ing out af­ter 27 years, and he’s be­ing re­placed by a com­pa­ny in­sid­er

Close to 3 years after Eli Lilly CEO Dave Ricks added the title of president of the US operations to Enrique Conterno’s resume, which included his helmsmanship of the diabetes franchise, the Peruvian born exec is set to retire after a 27-year run at the pharma giant.

Lilly put out the news just as it was posting Q3 results, with a mix of upbeat and downbeat results in the latest set of numbers from Lilly.
Conterno — a grizzled, deeply experienced and sometimes gruff veteran of the pharma world — was a high-profile figure at Lilly, stepping up to expanded duties as the company was forced to deal with intense pricing pressure on the diabetes side of the business. He had replaced outgoing US president Alex Azar, who later popped up as head of Health and Human Services in the Trump administration.
As head of the diabetes unit, Conterno had to deal with an extraordinarily competitive field as payers demanded bigger discounts. Trulicity’s success helped generate new revenue for the company, but Q3’s miss on revenue had a lot to do with the need for discounting the drug ahead of Novo Nordisk’s rival therapy, Rybelsus, which was priced on the wholesale level at an almost identical rate.

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No­var­tis hands off $80M in cash to part­ner up with a top biotech play­er in the fi­bro­sis sec­tor

Never underestimate the power of a good showing at a scientific conference.
In a presentation late last year, the researchers at Pliant Therapeutics launched a series of discussions about the preclinical data they were pulling together around their work on their small-molecule integrin inhibitor aimed at transforming growth factor beta, or TGF-β, a key pathway involved in fibrosis.
And they got some serious attention for the work.
“We got interest from pharma partners and at the end Novartis basically made it,” says Pliant CEO Bernard Coulie.

Is there a recipe for M&A suc­cess? The best and worst buy­out deals in the past decade of­fer some keys to suc­cess — and fail­ure

It’s not easy achieving a solid win in M&A in this industry. But if you follow a few simple guidelines, you may be able to increase your odds of success.
Geoffrey Porges and the team at SVB Leerink went about the “notoriously difficult” task of scoring the biopharma buyout of 2009 to 2019. Sizing up current and expected revenue from the products that were gained, they came up with the 5 winners:
Merck/Schering Plough
Bristol/Medarex
Gilead/Pharmasset
Sanofi/Genzyme
AstraZeneca/Acerta
It says a lot about the field that it’s much easier sorting out the 5 worst deals, though there’s also a lot more competition for that title, notes Porges. As picked by the analysts:
J&J/Actelion
Merck/Cubist
Alexion/Synageva
AbbVie/Stemcentrx
Gilead/Kite

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