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

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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Bris­tol My­ers is clean­ing up the post-Cel­gene merg­er pipeline, and they’re sweep­ing out an ex­per­i­men­tal check­point in the process

Back during the lead up to the $74 billion buyout of Celgene, the big biotech’s leadership did a little housecleaning with a major pact it had forged with Jounce. Out went the $2.6 billion deal and a collaboration on ICOS and PD-1.

Celgene, though, also added a $530 million deal — $50 million up front — to get the worldwide rights to JTX-8064, a drug that targets the LILRB2 receptor on macrophages.

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GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

UP­DAT­ED: Es­ti­mat­ing a US price tag of $5K per course, remde­sivir is set to make bil­lions for Gilead, says key an­a­lyst

Data on remdesivir — the first drug shown to benefit Covid-19 patients in a randomized, controlled trial setting — may be murky, but its maker Gilead could reap billions from the sales of the failed Ebola therapy, according to an estimate by a prominent Wall Street analyst. However, the forecast, which is based on a $5,000-per-course US price tag, triggered the ire of one top drug price expert.