IDO rout: Piv­otal tri­als with Bris­tol-My­ers, Mer­ck and As­traZeneca dumped in wake of In­cyte's PhI­II im­plo­sion

The IDO R&D pipeline is in dan­ger of be­ing ex­ter­mi­nat­ed.

In the wake of a piv­otal fail­ure of In­cyte’s $IN­CY lead IDO drug epaca­do­stat, Bris­tol-My­ers Squibb $BMY be­came the third play­er forced to re­trench in that im­muno-on­col­o­gy field, drop­ping three late-stage stud­ies of a ri­val drug it bagged in a $1.25 bil­lion buy­out. But that was just the start of a rout.

In­cyte re­port­ed this morn­ing that its wide-rang­ing col­lab­o­ra­tions with Big Phar­ma play­ers are com­ing un­done. In their Q1 an­nounce­ment, echo­ing the fail­ure of ECHO-301, the com­pa­ny not­ed:

En­roll­ment will be dis­con­tin­ued in the four ad­di­tion­al piv­otal tri­als of epaca­do­stat in com­bi­na­tion with pem­brolizum­ab (Mer­ck’s Keytru­da), and in the two piv­otal tri­als of epaca­do­stat in com­bi­na­tion with nivolum­ab (Bris­tol-My­ers’ Op­di­vo); each of these stud­ies will be amend­ed to en­able pa­tients and their physi­cians to con­sid­er al­ter­na­tive ther­a­peu­tic op­tions. The piv­otal tri­al in com­bi­na­tion with dur­val­um­ab (As­traZeneca’s Imfinzi) in Stage 3 lung can­cer will not be ini­ti­at­ed.

A spokesper­son for As­traZeneca al­so tells me that there is “an­oth­er Phase II (com­bi­na­tion study) in sol­id tu­mors and we’re go­ing to stop en­roll­ment there too.” That will be all for the ECHO-203 study — epaca­do­stat plus dur­val­um­ab again. “In­cyte did present some da­ta from ECHO-203 at AACR: 15 pa­tients with pan­cre­at­ic can­cer were en­rolled across mul­ti­ple dose lev­els, no clin­i­cal ac­tiv­i­ty was ob­served.”

In ad­di­tion, In­cyte said that it is “sig­nif­i­cant­ly down­siz­ing the epaca­do­stat de­vel­op­ment pro­gram,” sig­nal­ing a painful re­treat for a one-time star drug that com­mand­ed pro­jec­tions of block­buster peak sales.

Ac­cord­ing to clin­i­cal­tri­als.gov, in­ves­ti­ga­tors for the big biotech to­day ter­mi­nat­ed a Phase III study of BMS-986205 in com­bi­na­tion with Bris­tol-My­ers’ Op­di­vo for front­line head and neck can­cer. An­oth­er Phase III study for front­line Stage IV or re­cur­rent non-small cell lung can­cer us­ing BMS-986205 and Op­di­vo with or with­out chemo ver­sus chemo alone was with­drawn. And there’s a third study for melanoma that’s now ac­tive but not re­cruit­ing af­ter en­list­ing 72 pa­tients.

A spokesper­son for Bris­tol-My­ers told us Mon­day night:

Based on emerg­ing da­ta on the IDO path­way, we closed reg­is­tra­tional stud­ies of our IDO in­hibitor, BMS-986205, in melanoma, SC­CHN and NSCLC. We re­main com­mit­ted to con­tin­ued re­search of BMS-986205-based com­bi­na­tions in an in­formed and sci­en­tif­i­cal­ly ro­bust man­ner. We will con­tin­ue to eval­u­ate BMS-986205-based com­bi­na­tions in our Phase 1/2 study, CA017-003.

Sep­a­rate­ly, we are work­ing quick­ly with In­cyte to as­sess our pro­gram un­der the col­lab­o­ra­tion.

NewLink $NLNK was the first to over­haul its ap­proach on IDO fol­low­ing the In­cyte dis­as­ter.  The biotech scrapped a melanoma study that would have eval­u­at­ed in­dox­i­mod in com­bi­na­tion with check­point in­hibitors Keytru­da or Op­di­vo in 600 pa­tients. In a press re­lease, NewLink ex­plained the de­ci­sion was made “in the con­text of the fail­ure of a com­peti­tor’s tri­al of its en­zy­mat­ic IDO in­hibitor in a sim­i­lar clin­i­cal set­ting.

Bris­tol-My­ers’ de­ci­sion — first re­port­ed by Xcon­o­my — un­der­scores a grow­ing be­lief that In­cyte’s fail­ure was as much a fail­ure of the class as an in­di­vid­ual ther­a­py, po­ten­tial­ly tor­pe­do­ing a wide swath of clin­i­cal tri­als now in the pipeline.

In­cyte frankly con­ced­ed that its piv­otal fail­ure raised doubts about its en­tire ef­fort, which in­cludes a host of com­bi­na­tion stud­ies with check­point lead­ers like Mer­ck and As­traZeneca. In this case, Bris­tol-My­ers is cut­ting back on a drug that it ac­quired in a block­buster deal to ac­quire Flexus 3 years ago. In­ves­ti­ga­tors have re­peat­ed­ly tout­ed the drug as a po­ten­tial lynch­pin in im­muno-on­col­o­gy, fo­cus­ing on an en­zyme that sup­press­es the im­mune cells Op­di­vo and a whole new class of PD-1/L1 check­points are de­signed to un­leash in an at­tack on can­cer cells.

Iron­i­cal­ly, In­cyte has been pur­su­ing lit­i­ga­tion against one of its for­mer sci­en­tists, claim­ing he de­fect­ed to Flexus with IDO trade se­crets in hand, well be­fore the buy­out. Bris­tol-My­ers, though, has stead­fast­ly as­sert­ed — with some sup­port from an­a­lysts — that it had the bet­ter IDO that could leapfrog epaca­do­stat. The leap­ing in IDO, though, has stopped. At least for now.

The Fac­tors Dri­ving a Rapid Evo­lu­tion of Gene & Cell Ther­a­py and CAR-T Clin­i­cal Re­search in APAC

APAC is the fastest growing region globally for cell & gene therapy trials representing more than a third of all cell & gene studies globally, with China leading in the region. 

APAC is the leading location globally for CAR-T trials with China attracting ~60% of all CAR-T trials globally between 2015-2022. The number of CAR-T trials initiated by Western companies has rapidly increased in recent years (current CAGR of about 60%), with multiple targets being explored including CD19, CD20, CD22, BCMA, CD30, CD123, CD33, CD38, and CD138.

The End­points 11; blue­bird's $3M gene ther­a­py; Bio­gen tout new neu­ro da­ta; Harsh re­views for can­cer drugs; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Reading about John Carroll’s pick of biotech’s most promising startups has become a treasured tradition. If you ever get curious about previous classes of the Endpoints 11, you can find all of them (plus a number of our other regular specials) here.

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EMA warns of short­ages of two Boehringer heart drugs due to a spike in de­mand

The EMA is putting EU member states on alert over the shortage of two drugs that counter heart attacks due to an uptick in demand.

On Friday, the EMA sent out a warning that two Boehringer Ingelheim drugs are experiencing a shortage: Actilyse and Metalyse. The drugs are used as emergency treatments for adults experiencing acute myocardial infarction, or a heart attack, by dissolving blood clots that have formed in the blood vessels.

The End­points 11: The top pri­vate biotechs in pur­suit of new drugs. Push­ing the en­ve­lope with pow­er­ful new tech­nolo­gies

Right around the beginning of the year, we got a close-up look at what happens after a boom ripples through biotech. The crash of life sciences stocks in Q1 was heard around the world.

In the months since, we’ve seen the natural Darwinian down cycle take effect. Reverse mergers made a comeback, with more burned out shells to go public at a time IPOs and road shows are out of favor. And no doubt some of the more recent arrivals on the investing side of the business are finding greener pastures.

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As­traZeneca, Mer­ck cull one Lyn­parza in­di­ca­tion in heav­i­ly pre­treat­ed ovar­i­an can­cer pa­tients

Just one day after blockbuster Lynparza got access to another indication in China, its Big Pharma owners have decided to withdraw it in certain patients after reviewing Phase III data.

The two companies that work together on Lynparza decided to recall one of the indications several weeks ago in a specific type of ovarian cancer, Lynparza’s first indication when it was first FDA-approved in 2014. Initial data showed that rates of overall survival in patients with at least three rounds of chemo before getting on the PARP inhibitor were lower than in patients with less previous chemo treatment.

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Mene Pangalos (AstraZeneca via YouTube)

As­traZeneca shuts the PhI­II door for Ion­is' PC­SK9 drug de­spite pos­i­tive PhI­Ib

When Ionis and AstraZeneca unveiled the first round of mid-stage data for their antisense PCSK9 drug, Mene Pangalos, AstraZeneca’s EVP of biopharmaceuticals R&D, underscored the drug’s “potential best-in-class efficacy profile.”

But now that the second batch is in, it appears AZD8233 isn’t hitting the mark after all.

Ionis announced Friday morning that although the candidate, also dubbed ION449, met the primary endpoint in the Phase IIb SOLANO trial, its partners at AstraZeneca have decided not to move it into Phase III studies because the “results did not achieve pre-specified efficacy criteria.”

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Up­dat­ed: Bio­gen throws it­self back in­to mud­dled da­ta ar­gu­ments with more de­tails on its an­ti­sense ALS drug

With a highly watched FDA decision deadline coming in late January, Biogen and Ionis dropped the full data on the Phase III study of their ALS drug tofersen in the New England Journal of Medicine on Wednesday.

Biogen is looking for approval for tofersen in a very small subset of ALS patients — some 2%, according to the paper — who have a SOD1 gene mutation, which has previously been linked to ALS. Tofersen is meant to reduce levels of mutant SOD1 proteins.

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Fu­ji­film con­tin­ues CD­MO ex­pan­sion, break­ing ground on $435M UK site

Fujifilm’s CDMO arm, Fujifilm Diosynth, has been on a roll this month as the company has recently broken ground on a major project in Europe and it appears to be keeping up the momentum.

Fujifilm Diosynth announced that it has kicked off an expansion project for its microbial manufacturing facility at its campus in the town of Billingham, UK, in the northeast of England.

The 20,000 square-foot, £400 million ($435 million) expansion will add clean rooms, purification suites and a packing area along with more space for the manufacturing itself.

Solicitor General Elizabeth Prelogar

Should SCO­TUS hear Am­gen's Repatha case? So­lic­i­tor gen­er­al says no

Back in April, Amgen said it was encouraged by the solicitor general’s anticipated review of its Supreme Court petition to rehear a Repatha patent case. They’re likely much less optimistic about the outcome now.

Solicitor General Elizabeth Prelogar wrote in a recent 27-page brief that Amgen’s arguments “lack merit and further review is not warranted.”

The case traces back to a suit filed in 2014 against Sanofi and Regeneron’s Praluent, which ended up beating Amgen’s PCSK9 blockbuster Repatha to market by a month just a year later.