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

UP­DAT­ED: Mer­ck pulls Keytru­da in SCLC af­ter ac­cel­er­at­ed nod. Is the FDA get­ting tough on drug­mak­ers that don't hit their marks?

In what could be an early shot in the battle against drugmakers that whiff on confirmatory studies to support accelerated approvals, the FDA ordered Bristol Myers Squibb late last year to give up Opdivo’s approval in SCLC. Now, Merck is next on the firing line — are we seeing the FDA buckling down on post-marketing offenders?

Merck has withdrawn its marketing approval for PD-(L)1 inhibitor Keytruda in metastatic small cell lung cancer as part of what it describes as an “industry-wide evaluation” by the FDA of drugs that do not meet the post-marketing checkpoints on which their accelerated nods were based, the company said Monday.

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Michael Shpigelmacher

Khosla joins bet on un­con­ven­tion­al start­up look­ing to send drug de­liv­er­ing ro­bots in­to the brain

When Michael Shpigelmacher started the project, he knew he’d have to fund it himself. Every other effort of its kind was academic, rejected as too risky by investors.

Shpigelmacher, a robotics geek and entrepeneur who had drifted into consulting for pharma, wanted to build the real-life equivalent of technology from the 1960s film Fantastic Voyage, the one where a submarine crew is shrunk to “about the size of a microbe” and sent on a mission to repair a scientist’s brain. He scanned the literature, found the lab that was working on the most advanced project — at the Max Planck Institute in Germany, it turned out — and started funding them with money from his own account, along with some seed cash from friends and family.

Paul Sekhri

The next big biotech su­per­star? Paul Sekhri has some thoughts on that

It occasionally occurs to Paul Sekhri that if they pull this off, his company will be on the front page of the New York Times and a lead story in just about every major news outlet on the planet. He tries not to dwell on it, though.

“I just want to be laser-focused on getting to that point,” Sekhri says, before acknowledging, “Yes, it absolutely crossed my mind.”

Sekhri, a longtime biopharma executive with tenures at Sanofi and Novartis, is now entering year three as CEO of eGenesis, the biotech that George Church protégé Luhan Yang founded to genetically alter pigs so that they can be used for organ transplants. He led them through one megaround and has just closed another, raising $125 million from 17 different investors to push the first-ever (humanized) pig to human transplants into the clinic.

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Amit Munshi, Arena

One of Are­na's top drugs flops in a PhI­Ib study for IBS pain. But re­searchers tease out a pos­si­ble path for­ward as CEO ex­plores 's­trate­gic op­tion­s'

Four years ago, when Arena CEO Amit Munshi cut its ties to a troubled weight drug and doubled down on the pipeline, a cannabinoid receptor 2 agonist figured prominently in the biotech’s future. On Tuesday evening, however, Munshi’s high hopes for the drug took a nasty hit after it failed a Phase IIb study for patients with irritable bowel syndrome pain.

Put through a randomized pace with 273 patients, researchers said it flat failed the primary endpoint among the large group with abdominal pain. But they quickly went on to highlight subgroup data, always a tricky and controversial ploy, where they spotlighted a positive p value for patients with moderate to severe pain who received the high dose of the drug — one of 3 provided in the study.

Bob Nelsen (Photo by Michael Kovac/Getty Images)

With stars aligned and cash in re­serve, Bob Nelsen's Re­silience plans a makeover at 2 new fa­cil­i­ty ad­di­tions to its drug man­u­fac­tur­ing up­start

Bob Nelsen’s new, state-of-the-art drug manufacturing initiative is taking shape.

Just 3 months after gathering $800 million of launch money, a dream team board and a plan to shake up a field where he found too many bottlenecks and inefficiencies for the era of Covid-19, Resilience has snapped up a pair of facilities now in line for a retooling.

The company has acquired a 310,000-square-foot plant in Boston from Sanofi along with a 136,000-square-foot plant in Ontario to add to a network which CEO Rahul Singhvi says is just getting started on building his company’s operations up. The Sanofi deal comes with a contract to continue manufacturing one of its drugs.

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CEO Marco Taglietti (Scynexis)

'N­ev­er been more ur­gent:' Scynex­is looks to tack­le su­per­bug cri­sis with late-stage read­out for an­ti­fun­gal hope­ful

As the superbug crisis heats up around the world, Scynexis says it has new data from two interim analyses that prove its antifungal has the potential to treat a broad range of infections.

“The need for new anti-infectives capable of fighting the most resistant pathogens has never been more urgent as we confront the ongoing COVID-19 global pandemic,” CEO Marco Taglietti said in a statement.

A spot­light schiz­o­phre­nia drug in Neu­ro­crine's $2B Take­da deal flunks its first ma­jor test. But it's not giv­ing up yet

When Takeda spun out a pipeline of experimental psychiatry drugs to Neurocrine in a $2 billion deal amid a post-merger shakeout, R&D chief Andy Plump described the therapies as “very interesting but still difficult.”

On Tuesday, we got some idea of how difficult.

San Diego-based Neurocrine revealed that one of the three spotlight clinical programs they’d acquired failed the primary endpoint in a Phase II trial for schizophrenia, registering a negative outcome on the change from baseline in the positive and negative syndrome scale/negative symptom factor score (PANSS NSFS).

Af­ter bail­ing on Covid-19 vac­cines, Mer­ck will team up with J&J to pro­duce its shot as part of un­usu­al Big Phar­ma pact

Merck took a big gamble when it opted to jump into the Covid-19 vaccine race late, and made an equally momentous decision to back out in late January. Now, looking to chip in on the effort, Merck reportedly agreed to team up with one of the companies that has already crossed the finish line.

President Joe Biden on Tuesday is expected to announce a partnership between drugmakers Merck and Johnson & Johnson to jointly produce J&J’s recombinant protein Covid-19 vaccine that received the FDA’s emergency use authorization Saturday, the Washington Post reported.

Ab­b­Vie tees up a biotech buy­out af­ter siz­ing up their Parkin­son's drug spun out of Ke­van Shokat's lab

AbbVie has teed up a small but intriguing biotech buyout after looking over the preclinical work it’s been doing in Parkinson’s disease.

The company is called Mitokinin, a Bay Area biotech spun out of the lab of UCSF’s Kevan Shokat, whose scientific explorations have formed the academic basis of a slew of startups in the biotech hub. One of Shokat’s PhD students in the lab, Nicholas Hertz, co-founded Mitokinin using their lab work on PINK1 suggesting that amping up its activity could play an important role in regulating the mitochondrial dysfunction contributing to Parkinson’s disease pathogenesis and progression.

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