Keytru­da/epaca­do­stat com­bo crash­es in PhI­II melanoma study, rais­ing ques­tions about the fu­ture of IDO for In­cyte

A close­ly-watched Phase III study com­bin­ing Mer­ck’s PD-1 star Keytru­da with In­cyte’s IDO1 drug epaca­do­stat for metasta­t­ic melanoma has failed, cast­ing a pall over the fu­ture of this com­bi­na­tion ap­proach.

Ab­sent a sig­nif­i­cant im­prove­ment in pro­gres­sion-free sur­vival, as well as the like­ly fail­ure of the drug com­bi­na­tion to ex­tend over­all sur­vival, the in­ves­ti­ga­tors are halt­ing the study. In­cyte stuck with the top-line re­sults in their re­lease, promis­ing to roll out the full da­ta set lat­er. And they made it clear in a call with an­a­lysts this morn­ing that the ECHO-301 study fail­ure “has a neg­a­tive im­pact on the prob­a­bil­i­ty of suc­cess of the oth­er (com­bi­na­tion) stud­ies” — send­ing a shock wave through the I/O field.

In­cyte’s shares plunged 23% on the news, wip­ing out more than $3.5 bil­lion in mar­ket cap. The im­pli­ca­tions for oth­er IDO1 drugs al­so dam­aged oth­er com­pa­nies in the field, in­clud­ing NewLink $NLNK, down 44%, as well as Bris­tol-My­ers Squibb $BMY down 2.6%.

Steven Stein

Mer­ck is one of a slate of bio­phar­ma com­pa­nies to com­bine their check­points with In­cyte’s IDO drug, look­ing to im­prove pa­tients chances for liv­ing longer with can­cer. The fail­ure of this first late-stage test, af­ter stok­ing hopes for some ma­jor ad­vances, now leaves In­cyte’s drug $IN­CY in a pre­car­i­ous po­si­tion, cre­at­ing a cri­sis for CEO Hervé Hop­penot.

Epaca­do­stat was num­ber 3 on Eval­u­ate Phar­ma’s top 10 list of 2018 launch­es, with close to $2 bil­lion in pro­ject­ed peak sales es­ti­mates. And UBS an­a­lysts gave this study a 100% chance of suc­cess, not­ing the high ex­pec­ta­tions — and hype — fo­cused on this drug.

In­ves­ti­ga­tors tracked a haz­ard ra­tio of 1.00, which “leaves no doubt that in this study… the com­pound didn’t per­form,” said Steven Stein, the chief med­ical of­fi­cer, in the call. And there was no pos­i­tive glim­mer of hope seen in any sub­group analy­sis. “Giv­en those haz­ard ra­tios it is go­ing to be dif­fi­cult to dis­cern a sub­group with suf­fi­cient ef­fect.”

The fail­ure of the study al­so rais­es the chances that oth­er tri­als in the pro­gram may need to be ad­just­ed, he added, with pos­si­ble sta­tis­ti­cal and bio­mark­er mod­i­fi­ca­tions.

An­a­lysts had been en­cour­aged last sum­mer with the lat­est look at da­ta from a sin­gle-arm melanoma study, mak­ing this one of the most an­tic­i­pat­ed stud­ies of 2018. In­cyte faces a dif­fi­cult task now in re­build­ing hopes for a block­buster fu­ture as the field awaits a long string of read outs from com­bi­na­tion tri­als.

An­tic­i­pat­ing some big re­turns, a whole host of play­ers has dived in­to IDO. A re­cent study from the Can­cer Re­search In­sti­tute found that there were 18 IDOs in the pipeline. Epaca­do­stat was the most ad­vanced of them all, but there have been a num­ber of set­backs, in­clud­ing a pro­gram pur­sued by Genen­tech, which the com­pa­ny aban­doned af­ter see­ing weak re­sults. And a grow­ing line­up of fail­ures will boost fears that this is the wrong tar­get.

That woe­ful feel­ing didn’t help mat­ters at Bris­tol-My­ers, which has one of the most ad­vanced IDOs in the clin­ic af­ter In­cyte’s pro­gram. Bris­tol-My­ers paid $1.25 bil­lion to ob­tain their drug in the Flexus buy­out, which was im­pli­cat­ed in a suit In­cyte filed claim­ing that a for­mer staffer had stolen trade se­crets on their drug, hand­ing them off to Flexus. Sev­er­al an­a­lysts have out­lined rea­sons why they think that Bris­tol-My­ers has the bet­ter of the two drugs.

With the alarm bells ring­ing loud­ly all day Fri­day, NewLink re­spond­ed by putting out a re­lease as­sert­ing that its drug in­dox­i­mod had a “dif­fer­en­ti­at­ed mech­a­nism of ac­tion.” The biotech al­so said that it would do a re­view of its pro­grams in light of the set­back at In­cyte.

The failed study will help gain “un­der­stand­ing of the role of IDO1 in­hi­bi­tion in com­bi­na­tion with PD-1 an­tag­o­nists, and may in­form our broad­er epaca­do­stat clin­i­cal de­vel­op­ment pro­gram,” said Steven Stein, chief med­ical of­fi­cer, In­cyte. “We re­main ded­i­cat­ed to trans­form­ing the treat­ment of can­cer and will con­tin­ue to ex­plore how IDO1 in­hi­bi­tion and oth­er nov­el mech­a­nisms can po­ten­tial­ly im­prove out­comes for pa­tients in need.”


Im­age: Hervé Hop­penot, In­cyte CEO at an End­points News event, Jan­u­ary 2018. END­POINTS NEWS

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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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.