Merck’s Keytruda scores first win in adjuvant kidney cancer, giving it a leg up on checkpoint inhibitor rivals

Mer­ck is mak­ing room for yet an­oth­er use on its Keytru­da la­bel — this time, as the first ad­ju­vant im­munother­a­py for cer­tain re­nal cell car­ci­no­ma pa­tients af­ter they’ve had kid­ney surgery.

The FDA has ap­proved Keytru­da in the ad­ju­vant set­ting three weeks be­fore its goal date, mark­ing the lat­est in a streak of la­bel ex­pan­sions and giv­ing the PD-1 su­per­star a leg up on its check­point in­hibitor ri­vals.

The news comes al­most half a year af­ter Mer­ck took the stage at AS­CO to re­port on Phase III da­ta show­ing Keytru­da cut the risk of can­cer re­lapse or death by 32% com­pared to place­bo, hit­ting the pri­ma­ry end­point of dis­ease-free sur­vival. Reg­u­la­tors say their de­ci­sion was based on da­ta show­ing a 22% rate of events in the Keytru­da arm (de­fined as re­cur­rence, metas­ta­sis or death), ver­sus 30% in the place­bo arm (p=0.001). Over­all sur­vival da­ta were not ma­ture at the time of the analy­sis, ac­cord­ing to the FDA.

The study, dubbed KEYNOTE-564, en­rolled 994 RCC pa­tients at in­ter­me­di­ate-high or high risk of re­cur­rence af­ter a kid­ney re­moval, or af­ter re­moval of a kid­ney and metasta­t­ic le­sions.

While Keytru­da is al­ready ap­proved in com­bi­na­tion with Pfiz­er’s In­ly­ta for first-line RCC, Mer­ck sought to ex­pand in­to even ear­li­er, post-surgery use. In on­col­o­gy, an ad­ju­vant ther­a­py is one that’s ap­plied af­ter ini­tial treat­ment to sup­press sec­ondary tu­mor for­ma­tion. Mer­ck tout­ed KEYNOTE-564 as the first late-stage win for a check­point in­hibitor in ad­ju­vant kid­ney can­cer.

That’s not to say that oth­ers aren’t try­ing. Bris­tol My­ers Squibb is cur­rent­ly test­ing its an­ti-PD-(L)1 chal­lenger Op­di­vo alone and in com­bi­na­tion with Yer­voy for can­cer pa­tients who have re­moved part of a kid­ney. Roche is al­so test­ing Tecen­triq in the ad­ju­vant set­ting here, and ex­pects to file next year. Mean­while, Mer­ck has faced some push­back in oth­er ear­li­er set­tings, most no­tably its KEYNOTE-522 study in neoad­ju­vant/ad­ju­vant triple-neg­a­tive breast can­cer. That study re­ceived an over­whelm­ing thumbs-down from the mem­bers of an FDA ad­vi­so­ry com­mit­tee in Feb­ru­ary, af­ter ex­press­ing con­cerns about a lack of ma­ture event-free sur­vival da­ta and OS fig­ures. The FDA end­ed up hand­ing the drug a CRL in that pop­u­la­tion — but weeks lat­er, Mer­ck un­corked some da­ta demon­strat­ing a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in event-free sur­vival com­pared to the con­trol.

‘Now that we are see­ing the da­ta ma­ture af­ter four years to in­clude a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in event-free sur­vival, we look for­ward to work­ing with the FDA and oth­er glob­al au­thor­i­ties,’ Roy Baynes, CMO of Mer­ck Re­search Lab­o­ra­to­ries, said at the time.

For years, paper-based processes and individual point solutions dominated the clinical research landscape, and patient participation in clinical trials was largely an in-person engagement. But when the COVID-19 pandemic took a stronghold, traditional clinical trial methods emerged as inadequate, putting clinical trials and the life sciences industry at a crossroads. Practically overnight, the industry had to rapidly shift to decentralized clinical trial methods, while maintaining data quality and regulatory compliance.

Douglas Fambrough, Dicerna CEO (Dicerna via YouTube)

Early this year researchers at Novo Nordisk were beaming as they announced the first drug identified in their RNAi alliance with Dicerna was headed into the clinic. And now they’re coming back for the whole thing.

This morning the Copenhagen-based pharma giant put out word that it is buying Dicerna $DRNA — an RNAi pioneer that has had its up and downs over the years — for $3.3 billion. Novo is paying $38.25 a share — an 80% premium.

Unlock this story instantly and join 123,500+ biopharma pros reading Endpoints daily — and it’s free.

Gilead is going all in — hook, line and sinker — on its oncology alliance with Arcus. And they are going for broke.

The big biotech unveiled a deal that now delivers $725 million in opt-in payments covering the clinical development programs for Arcus, ranging from their closely watched anti-TIGIT programs for domvanalimab and AB308 to etrumadenant (the A2a/A2b adenosine receptor antagonist) and quemliclustat, the small molecule CD73 inhibitor. Gilead will also cover half of the development costs, handing Terry Rosen’s biotech a deal that gives them a clear cash runway to achieving all its goals in oncology.

Unlock this story instantly and join 123,500+ biopharma pros reading Endpoints daily — and it’s free.

Protein degradation is one of the hot drug classes of the future, but competitors are piling in with the likes of C4, Arvinas, Frontier Medicines and Vividion jostling for position. A new startup wants to apply the lessons learned from degradation outside the cell, and it now has the greenlight from RA Capital to steam ahead.

Avilar Therapeutics launched Thursday with $60 million from founding investor RA to chase a novel protein degradation drug class the startup is calling ATACs— short for ‘ASGPR Targeting Chimeras’ — that looks to trash unwanted proteins circulating outside the human cell.

Catherine Stehman-Breen and Vic Myer, Chroma CEO and CSO

A handful of the world’s most prominent gene editing-focused academics have been working for over a year on a new company built around a new approach for modifying DNA to treat disease. Known as Chroma Medicine, it launched on Wednesday with $125 million in early funding from Atlas, Newpath, Cormorant and several other VCs.

Chroma will focus on a markedly different way of modifying the genome than most of the gene editing biotechs that have arisen since CRISPR was pioneered nearly a decade ago. Instead of trying to erase or rewrite portions of a patient’s actual DNA — those As, Ts, Cs and Gs — Chroma will try to change the way that DNA is expressed in the cell.

Unlock this story instantly and join 123,500+ biopharma pros reading Endpoints daily — and it’s free.

A few weeks after Jennifer Doudna introduced CRISPR/Cas9 genome editing to the world, one of her old students decided to take the central part of the biology-altering invention and kill it.

CRISPR/Cas9, as the name implies, is a two-part system: a string of letters called a guide RNA, that says where to cut the DNA. And an enzyme, Cas9, that does the cutting. Often compared to molecular scissors, it was the first system that allowed researchers to cut DNA with ease and precision, promising potential cures for genetic diseases such as sickle cell and cystic fibrosis.

Unlock this article along with other benefits by subscribing to one of our paid plans.

The House Energy & Commerce Committee began marking up a dozen bills on Wednesday morning including one that would require the FDA to craft a five-year action plan for fostering the development of drugs that improve or extend the lives of people living with rare neurodegenerative diseases.

Rare neurodegenerative diseases, like amyotrophic lateral sclerosis or ALS, have been historically very difficult to treat. But this bipartisan bill, introduced by Rep. Mike Quigley (D-IL), will provide $100 million for each of fiscal years 2022 through 2026 to help HHS award grants to facilitate access to investigational drugs that diagnose or treat ALS.

Rep. Diana DeGette (D-CO) (Alex Brandon/AP Images)

Reps. Fred Upton (R-MI) and Diana DeGette (D-CO) on Tuesday unveiled the second iteration of their mammoth 21st Century Cures Act, a wide-ranging, mostly pro-pharma law signed by former President Obama that pushed the FDA in certain directions on real-world data and other hot button issues.

This time around there’s a provision to fund a $6.5 billion (on par with Biden’s request) research center at NIH to speed new treatments and make riskier investments. Similar to DARPA, the new NIH division to be known as ARPA-H, would be run by a small group of program managers with more latitude to pursue high-risk, high-reward projects.

Unlock this article along with other benefits by subscribing to one of our paid plans.

Mene Pangalos (AstraZeneca via YouTube)

New follow-up data suggest that AstraZeneca’s long-acting antibody can protect high-risk populations from contracting Covid-19 for as long as six months, beefing up the case for it as a form of ‘passive immunization’ or ‘passive vaccination.’

At a six-month cutoff for the Phase III PROVENT trial, investigators tracked an 83% reduction in risk of symptomatic Covid-19 after one dose of the antibody among 4,991 volunteers. The company did not spell out case counts on either arm, noting only that there were no severe disease or Covid-related deaths in the AZD7442 arm and two additional cases of severe Covid-19 in the placebo arm (for a total of five severe cases and two related deaths).
https://endpts.com/mercks-keytruda-scores-first-win-in-adjuvant-kidney-cancer-giving-it-a-leg-up-on-checkpoint-inhibitor-rivals/