Merck Research Laboratories CMO Roy Baynes

Mer­ck­'s Keytru­da un­corks full da­ta on lat­est ad­ju­vant win — this time in melanoma — adding bricks to ear­ly can­cer wall

In re­cent months, the bat­tle for PD-(L)1 dom­i­nance has spilled over in­to ear­ly can­cer with Mer­ck’s Keytru­da and Bris­tol My­ers Squibb’s Op­di­vo all alone on the front lines. Keytru­da now has an­oth­er shell in its ban­dolier, and it could spell a quick ap­proval.

Keytru­da cut the risk of re­lapse or death by 35% over place­bo (p=0.00658) in high-risk, stage 2 melanoma pa­tients who had pre­vi­ous­ly un­der­gone surgery to re­move their tu­mors, ac­cord­ing to full da­ta from the Phase III KEYNOTE-716 pre­sent­ed Sat­ur­day at #ES­MO21.

It’s Keytru­da’s lat­est win in what is known as ad­ju­vant/neoad­ju­vant can­cer, mak­ing good on Mer­ck’s mis­sion to bring its block­buster PD-1 in­hibitor in­to pa­tients be­fore their can­cer ever ad­vances. The FDA ac­cept­ed these da­ta for pri­or­i­ty re­view in Au­gust.

At a 14.4-month in­ter­im check-in, 11.1% of 487 pa­tients dosed with Keytru­da had re­lapsed or died com­pared with 16.8% of pa­tients on place­bo in the ran­dom­ized test. The Keytru­da arm saw few­er “dis­tant re­cur­rences” at 4.7% of pa­tients com­pared with 7.8% in the place­bo arm.

Mer­ck Re­search Labs CMO and Keytru­da czar Roy Baynes had this to say about the re­sults:

We con­duct­ed KEYNOTE-716 to ex­plore whether ad­ju­vant Keytru­da, an ap­proved ad­ju­vant treat­ment op­tion across all re­sect­ed stage III melanoma, could pro­long re­cur­rence-free sur­vival for pa­tients with re­sect­ed high-risk stage II dis­ease. These find­ings of a sig­nif­i­cant 35% re­duc­tion in the risk of dis­ease re­cur­rence or death com­pared to place­bo sup­port ear­li­er in­ter­ven­tion with Keytru­da. We are pleased that these find­ings have been ac­cept­ed for pri­or­i­ty re­view by the FDA, and we are grate­ful to the in­ves­ti­ga­tors and pa­tients for their in­volve­ment in this im­por­tant study.

Ear­ly can­cer has emerged as a key bat­tle­field for the biggest I/O play­ers, with drugs such as Keytru­da and Bris­tol My­ers Squibb’s Op­di­vo set­tling in as stan­dards of care across ad­vanced can­cer and squab­bling over rel­a­tive­ly mi­nor in­di­ca­tions. But ad­ju­vant/neoad­ju­vant can­cer — and the po­ten­tial to prove im­mune check­point in­hibitors can be cu­ra­tive op­tions — has dri­ven those two biggest play­ers in­to a heat­ed con­test for pa­tients, with big rev­enues on the line.

Mer­ck toplined da­ta from the 716 study back in Au­gust, just days af­ter the megablock­buster earned the FDA’s ap­proval to head in­to ear­ly breast can­cer pa­tients. The agency gave its rub­ber stamp to a reg­i­men of Keytru­da plus chemo as a neoad­ju­vant com­bo fol­lowed by ad­ju­vant Keytru­da monother­a­py in pa­tients with high-risk triple-neg­a­tive breast can­cer.

The da­ta un­der­scor­ing that ap­proval were par­tic­u­lar­ly con­tentious: FDA hand­ed Mer­ck a com­plete re­sponse let­ter on the re­sults, cit­ing a lack of ma­ture safe­ty da­ta and ques­tions over the piv­otal study’s patho­log­ic com­plete re­sponse end­point. But Mer­ck with­in weeks rolled out OS da­ta show­ing a win on more ma­ture sur­vival da­ta, and caus­ing the FDA to re­verse its ear­li­er de­ci­sion.

In ear­ly June, Mer­ck rolled out da­ta from the KEYNOTE-564 study for Keytru­da in ad­ju­vant kid­ney can­cer, with the drug cut­ting the risk of can­cer re­lapse or death by 32% af­ter a lit­tle more than two years com­pared with place­bo in re­nal cell car­ci­no­ma pa­tients with a mid-to-high risk of re­cur­rence af­ter a kid­ney re­moval, or af­ter re­moval of a kid­ney and metasta­t­ic le­sions.

Mean­while, Op­di­vo sports an ad­ju­vant ap­proval of its own from May in re­sect­ed esophageal or gas­troe­sophageal junc­tion (GEJ) can­cer with resid­ual patho­log­ic dis­ease in pa­tients who have re­ceived neoad­ju­vant chemora­dio­ther­a­py. The ap­proval was based on re­sults from the Phase III CHECK­MATE-577 study, which found a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in dis­ease-free sur­vival (DFS) over place­bo, which was de­fined as the time be­tween ran­dom­iza­tion and the first re­cur­rence date, or death, from any cause.

A month be­fore, the FDA grant­ed pri­or­i­ty re­view to Op­di­vo as an ad­ju­vant treat­ment in mus­cle-in­va­sive urothe­lial can­cer.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

So — that pig-to-hu­man trans­plant; Po­ten­tial di­a­betes cure reach­es pa­tient; Ac­cused MIT sci­en­tist lash­es back; 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.

We’re incredibly excited to welcome Beth Bulik, seasoned pharma marketing reporter, to the team. You can find much of her work in our new Marketing channel — and in her weekly newsletter, Endpoints PharmaRx, which will launch in early November. Add it to your subscriptions here.

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NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

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No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty


I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

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How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data are messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data are exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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David Livingston (Credit: Michael Sazel for CeMM)

Renowned Dana-Far­ber sci­en­tist, men­tor and bio­phar­ma ad­vi­sor David Liv­ingston has died

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.

Pascal Soriot, AstraZeneca CEO (via Getty images)

UP­DAT­ED: FDA slaps As­traZeneca's MCL-1 can­cer drug with a hold af­ter safe­ty is­sue — 2 years af­ter Am­gen axed a trou­bled ri­val

There are new questions being posed about a class of cancer drugs in the wake of the second FDA-enforced clinical hold in the field.

Two years after the FDA hit Amgen with a clinical hold on its MCL-1 inhibitor AMG 397 following signs of cardiac toxicity, AstraZeneca says that regulators hit them with a hold on their rival therapy of the same class.

The pharma giant noted on that its Phase I/II study for the MCL-1 drug AZD5991 “has been put on hold to allow further evaluation of safety related information.”

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Sur­geons suc­cess­ful­ly at­tach pig kid­ney to a hu­man for the first time, us­ing tech from Unit­ed's Re­vivi­cor

In a first, researchers reportedly successfully transplanted a pig kidney into a human without triggering an immediate immune response this week. And the technology came from the biotech United Therapeutics.

Surgeons spent three days attaching the kidney to the patient’s blood vessels, but when all was said and done, the kidney appeared to be functioning normally in early testing, Reuters and the New York Times were among those to report. The kidney came from a genetically altered pig developed through United’s Revivicor unit.

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