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

Paul Hudson, Getty Images

UP­DAT­ED: Sanofi CEO Hud­son lays out new R&D fo­cus — chop­ping di­a­betes, car­dio and slash­ing $2B-plus costs in sur­gi­cal dis­sec­tion

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy presentation Tuesday with a tell-tale deal to buy Synthorx for $2.5 billion. That fits squarely with hints that he’s pointing the company to a bigger future in oncology, which also squares with a major industry tilt.

In a big reveal later in the day, though, Hudson offered a slate of stunners on his plans to surgically dissect and reassemble the portfoloio, saying that the company is dropping cardio and diabetes research — which covers two of its biggest franchise arenas. Sanofi missed the boat on developing new diabetes drugs, and now it’s pulling out entirely. As part of the pullback, it’s dropping efpeglenatide, their once-weekly GLP-1 injection for diabetes.

“To be out of cardiovascular and diabetes is not easy for a company like ours with an incredibly proud history,” Hudson said on a call with reporters, according to the Wall Street Journal. “As tough a choice as that is, we’re making that choice.”

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De­vel­op­ment of the Next Gen­er­a­tion NKG2D CAR T-cell Man­u­fac­tur­ing Process

Celyad’s view on developing and delivering a CAR T-cell therapy with multi-tumor specificity combined with cell manufacturing success
Overview
Transitioning potential therapeutic assets from academia into the commercial environment is an exercise that is largely underappreciated by stakeholders, except for drug developers themselves. The promise of preclinical or early clinical results drives enthusiasm, but the pragmatic delivery of a therapy outside of small, local testing is most often a major challenge for drug developers especially, including among other things, the manufacturing challenges that surround the production of just-in-time and personalized autologous cell therapy products.

What does $6.9B buy these days in on­col­o­gy R&D? As­traZeneca has a land­mark an­swer

Given the way the FDA has been whisking through new drug approvals months ahead of their PDUFA date, AstraZeneca and their partners Daiichi Sankyo may not have to wait until Q2 of next year to get a green light on trastuzumab deruxtecan (DS-8201).

The pharma giant this morning played their ace in the hole, showing off why they were willing to commit to a $6.9 billion deal — with $1.35 billion in a cash upfront — to partner on the drug.

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FDA in-house re­view spot­lights an is­sue with one of Hori­zon's end­points but notes ef­fi­ca­cy for lead drug

The FDA in-house review highlights a disagreement of investigators’ use of a key endpoint by Horizon Pharma in the late-stage trial for the top drug in its pipeline, but largely agreed that the antibody was effective.

Horizon submitted a BLA for thyroid eye disease (TED) drug teprotumumab in March, less than two years after they bought the drug (and the rest of a division) from Narrow River for $145 million upfront. With breakthrough status, priority review, orphan designation and in-house sales projections of up to $750 million, the one-time Roche reject became the marquee pipeline asset for a company that’s developed some of the world’s most expensive drugs.

Seat­tle Ge­net­ics de­tails pos­i­tive OS and PFS da­ta for tu­ca­tinib in breast can­cer

Seattle Genetics $SGEN is showing off more positive data around tucatinib, its pivotal-stage drug for HER2 positive breast cancer.

A month after hearing about solidly upbeat hazard ratios, we learned today that the estimated progression-free survival rate at one year was 33% in the tucatinib arm compared to 12% for patients taking trastuzumab and capecitabine alone.

Median PFS was 7.8 months (95% CI: 7.5, 9.6) in the tucatinib arm, compared to 5.6 months (95% CI: 4.2, 7.1) in the control arm.

Bat­tered, cash hun­gry In­tec feels the burn of No­var­tis re­jec­tion

It’s a case of some bad timing for Intec.

Just when a key trial testing the company’s Accordion drug delivery tech imploded in Parkinson’s disease, they handed Novartis data from a successful PK study of a custom Accordion pill engineered to deliver a Novartis compound to entice the Swiss drugmaker into signing a licensing agreement.

Novartis said thanks, but no thanks.

For the cash-strapped Israeli drug developer, the failure to clinch the deal marks a big blow. As of the third quarter, the company has $15.7 million in cash and equivalents, which HC Wainwright analysts estimate will keep the lights on into mid-2020.

Bris­tol-My­ers shows off a low-pro­file AML con­tender it gained from Cel­gene buy­out — and they’re tak­ing it straight to the FDA

Bristol-Myers Squibb reaped an enormous pipeline with its much-criticized $64 billion megadeal to buy Celgene. And it got a few hidden gems in the deal.

One of those gems was brought out for display on Tuesday, with a late-breaker at ASH on CC-486, which is now being prepped for regulatory filings at the FDA and elsewhere.

Celgene top-lined the positive results in a maintenance setting for acute myeloid leukemia a few months ago, but at ASH investigators pulled back the curtains on the all-important data they believe will give them an advantage in the commercial wars to come.

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De­sert­ed by Astel­las and Mer­ck, lit­tle Cor­re­vio still can't win over FDA pan­el con­cerned with its AFib drug's safe­ty

When the FDA spurned Astellas’ pitch for atrial fibrillation drug vernakalant in 2008, regulators made it abundantly clear that it wasn’t the efficacy they had a problem with — two Phase III trials had shown the drug successfully restored 52% of patients’ heartbeat from irregular to normal — but the cardio safety issues for a drug that was to compete with well established, low-risk options. One licensing deal, one clinical hold and several studies later, the chances of approval aren’t looking any better.

New trade deal knocks out long-sought bi­o­log­ics pro­tec­tions for drug­mak­ers

House Democrats negotiating with the Trump Administration on a new North American trade deal settled early on four issues: enforcement, labor and environmental standards and drug pricing.

On drug pricing, Politico reports, Trump crumbled within weeks of heightened negotiations.

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