Mer­ck­'s Keytru­da makes the cut as a sec­ond-line monother­a­py for cer­tain esophageal can­cer pa­tients

Mer­ck’s cor­ner­stone check­point in­hibitor Keytru­da has added an­oth­er jew­el to its crown.

The US drug­mak­er on Wednes­day dis­closed that the PD-1 drug had won ap­proval as a monother­a­py for pa­tients with re­cur­rent lo­cal­ly ad­vanced or metasta­t­ic squa­mous cell car­ci­no­ma of the esoph­a­gus, whose tu­mors ex­press PD-L1, and whose dis­ease has pro­gressed de­spite one or more pri­or lines of sys­temic ther­a­py.

About 17,650 new esophageal can­cer cas­es will be di­ag­nosed this year in the Unit­ed States, the Amer­i­can Can­cer So­ci­ety es­ti­mates. Typ­i­cal­ly, pa­tients with the ad­vanced form of the dis­ease have lim­it­ed treat­ment op­tions.

The ap­proval was based on the KEYNOTE-181 study, which test­ed the drug ver­sus chemother­a­py in a broad group of 628 pre­vi­ous­ly-treat­ed pa­tients with re­cur­rent lo­cal­ly ad­vanced or metasta­t­ic esophageal can­cer. The main goal of the study — over­all sur­vival — was met on­ly in a sub­group of pa­tients, in pa­tients whose tu­mors ex­press PD-L1.

In its Jan­u­ary up­date, the com­pa­ny said that Keytru­da re­duced the risk of death by 31% in pa­tients with squa­mous cell car­ci­no­ma or ade­no­car­ci­no­ma in the study. The sub­group with PD-L1-pos­i­tive pa­tients — which con­sti­tut­ed 222 pa­tients — achieved a me­di­an OS of 9.3 months ver­sus 6.7 months for the chemother­a­py group. They al­so had a 12-month OS rate of 43% while the chemother­a­py arm ex­pe­ri­enced 20%.

How­ev­er, for the in­ten­tion-to-treat pop­u­la­tion, the dif­fer­ence in OS be­tween the two arms was not sta­tis­ti­cal­ly sig­nif­i­cant. In the 401 pa­tient sub­group of squa­mous cell car­ci­no­ma pa­tients, the Keytru­da group ex­pe­ri­enced a me­di­an OS of 8.2 months, com­pared to 7.1 months for the chemother­a­py arm — an­oth­er non-sta­tis­ti­cal­ly sig­nif­i­cant dif­fer­ence.

Da­ta from the KEYNOTE-180 study, which in­clud­ed 121 pa­tients with lo­cal­ly ad­vanced or metasta­t­ic esophageal can­cer who pro­gressed on or af­ter at least two pri­or sys­temic treat­ments for ad­vanced dis­ease, al­so con­tributed to the ap­proval, Mer­ck said.

Mer­ck $MRK is al­so run­ning a sep­a­rate Phase III study — dubbed KEYNOTE-590 — pit­ting Keytru­da in com­bi­na­tion with chemother­a­py as a first-line treat­ment in pa­tients with esophageal car­ci­no­ma. The tri­al is ex­pect­ed to wrap up next month.

Mean­while, oth­er check­point ri­vals — from Bris­tol-My­ers Squibb $BMY and BeiGene — are lin­ing up to tack­le the no­to­ri­ous­ly hard-to-treat can­cer.

Keytru­da, which is ap­proved for a pletho­ra of can­cers, has ce­ment­ed its crown in the field of im­muno-on­col­o­gy. It gen­er­at­ed $2.6 bil­lion in sec­ond-quar­ter rev­enue, up 58% over the same pe­ri­od a year ago.

The drug is on track to eclipse $10.6 bil­lion in sales by the end of the year — which is more than 50% over what it gen­er­at­ed in 2018 — and to sur­pass $20 bil­lion by 2024, Mizuho an­a­lysts wrote in a note.

Keytru­da was once seen as an un­der­dog to Bris­tol-My­ers’ pi­o­neer­ing Op­di­vo, but a string of tri­al fail­ures left Op­di­vo in the back­seat and Keytru­da as the dri­ving force. Now, some wor­ry that Mer­ck may be lean­ing too heav­i­ly on its key­stone as­set, but the com­pa­ny’s R&D chief Roger Perl­mut­ter is work­ing on but­tress­ing the com­pa­ny’s pipeline with a string of ac­qui­si­tions to mit­i­gate those con­cerns.

“While KEYTRU­DA is grow­ing in dom­i­nance, both in the mar­ket and on MRK’s P&L, we see MRK as hav­ing con­sid­er­able run­way (2028 LOE) to ad­dress con­cerns re­gard­ing con­cen­tra­tion of rev­enue,” Mizuho an­a­lysts added.

So­cial im­age: Shut­ter­stock

Mov­ing Out of the Clin­ic with Dig­i­tal Tools: Mo­bile Spirom­e­try Dur­ing COVID-19 & Be­yond

An important technology in assessing lung function, spirometry offers crucial data for the diagnosis and monitoring of pulmonary system diseases, as well as the ongoing measurement of treatment efficacy. But trends in the healthcare industry and new challenges introduced by the COVID-19 pandemic are causing professionals in clinical practice and research to reevaluate spirometry’s deployment methods and best practices.

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Sanofi, Glax­o­SmithK­line jump back in­to the PhI­II race for a Covid vac­cine — as the win­ners con­gre­gate be­hind the fin­ish line

Sanofi got out early in the race to develop a vaccine using more of a traditional approach, then derailed late last year as their candidate failed to work in older people. Now, after likely missing the bus for the bulk of the world’s affluent nations, they’re back from that embarrassing collapse with a second attempt using GSK’s adjuvant that may get them back on track — with a potential Q4 launch that the rest of the world will be paying close attention to.

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SCO­TUS de­clines to re­view En­brel biosim­i­lar case, tee­ing up 30+ years of ex­clu­siv­i­ty and $20B more for Am­gen’s block­buster

As the House Oversight Committee is set to grill AbbVie CEO Richard Gonzalez on Tuesday over tactics to block competition for its best-selling drug of all time, another decision on Capitol Hill on Monday opened the door for billions more in Amgen profits over the next eight years.

The Supreme Court on Monday denied Novartis subsidiary Sandoz’s petition to review a Federal Circuit’s July 2020 decision concerning its biosimilar Erelzi (etanercept-szzs), which FDA approved in 2016 as a biosimilar to Amgen’s Enbrel (etanercept). Samsung’s Enbrel biosimilar Eticovo also won approval in 2019 and remains sidelined.

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No­var­tis' En­tresto takes its 2nd fail­ure of the week­end at ACC, show­ing no ben­e­fit in most dire heart fail­ure pa­tients

Novartis’ Entresto started the ACC weekend off rough with a trial flop in heart attack patients, slowing the drug’s push into earlier patients. Now, an NIH-sponsored study is casting doubt on Entresto’s use in the most severe heart failure patients, another black mark on the increasingly controversial drug’s record.

Entresto, a combination of sacubitril and valsartan, could not beat out valsartan alone in an outcomes head-to-head for severe heart failure patients with a reduced ejection fraction (HFrEF), according to data presented Monday at the virtual American College of Cardiology meeting.

How to man­u­fac­ture Covid-19 vac­cines with­out the help of J&J, Pfiz­er or Mod­er­na? Bi­ol­yse sees the dif­fi­cul­ties up close

When Biolyse, an Ontario-based manufacturer of sterile injectables, forged a deal with Bolivia last week to manufacture up to 50 million J&J Covid-19 vaccine doses, the agreement kicked off what will prove to be a test case for how difficult the system of compulsory licenses is to navigate.

The first problem: When Biolyse asked J&J, via a March letter, to license its Covid-19 vaccine, manufacture it in Canada and pay 5% royalties on shipments to needy, low-income countries, J&J rejected the offer, refusing to negotiate. J&J also did not respond to a request for comment.

Tim Mayleben (L) and Sheldon Koenig (Esperion)

On the heels of a sting­ing Q1 set­back, Es­pe­ri­on's long­time cham­pi­on is ex­it­ing the helm and turn­ing the wheel over to a mar­ket­ing pro

Just days after getting stung by criticism from a badly disappointed group of analysts, there’s a big change happening today at the helm of Esperion $ESPR.

Longtime CEO Tim Mayleben, who championed the company for 9 years from early clinical through a lengthy late-stage drive to successfully get their cholesterol drug approved for a significant niche of patients in the US, is out of the C suite, effective immediately. Sheldon Koenig — hired at the end of 2020 with a resume replete with Big Pharma CV sales experience —  is stepping into his place, promising to right a badly listing commercial ship that’s been battered by market forces.

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Matt Gline (L) and Vivek Ramaswamy

In­sid­er ac­count of Roivan­t's SPAC deal — and that $7.3B val­u­a­tion — re­veals a few se­crets as Matt Gline po­si­tions the com­pa­ny as the new ‘Big Phar­ma’

It was Oct. 7, 2020, and Matt Gline wasn’t wasting any time.

The CEO of Roivant had word that KKR vet Jim Momtazee’s SPAC had priced late the night before, triggering a green light for anyone interested in pursuing a big check for future operations and riding the financial instrument to Nasdaq. So he wrote a quick email congratulating Momtazee, whom he knew, for the launch.

Oh, and maybe Momtazee would like to schedule something with Gline and his executive chairman, Roivant founder Vivek Ramaswamy, to chat about Roivant and its business?

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Re­gen­eron's Evkeeza shows promise in curb­ing high triglyc­erides, but will ge­net­ic dis­par­i­ties lim­it use?

When Regeneron scored an early approval for lipid lowering antibody Evkeeza back in February, the drugmaker cracked open a new pathway to lower abnormally high cholesterol levels. Now, Regeneron is chasing high triglycerides as well with some promising mid-stage data — but will genetic restrictions limit the drug’s use?

Regeneron’s Evkeeza (evinacumab) cut median triglyceride levels by more than 800 mg/dL (57%) in patients with a rare disorder causing abnormally high triglyceride levels compared with an overall increase of 50 mg/dL (1.8%) in participants on placebo, according to Phase II data presented Sunday at the virtual American College of Cardiology meeting.

$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; and more

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I still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

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