Merck CEO Robert Davis

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 as well as Ei­sai’s Lenvi­ma 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 Phase III 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.

Roy Baynes

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.

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

All about Omi­cron; We need more Covid an­tivi­rals; GSK snags Pfiz­er’s vac­cine ex­ec; Janet Wood­cock’s fu­ture at FDA; and more

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Usama Malik

Ex-Im­munomedics CFO charged with in­sid­er trad­ing, faces up to 20 years in prison af­ter al­leged­ly tip­ping off girl­friend and rel­a­tives of a PhI­II suc­cess

The former CFO of Immunomedics, who helped steer the company to its $21 billion buyout by Gilead last year, has been charged with insider trading, the Department of Justice announced Thursday.

Usama Malik tipped off his then-girlfriend and four others that a Phase III study for Trodelvy would be stopped early four days before Immunomedics publicly announced the result in April 2020, DoJ alleged in its complaint. The individuals then purchased Immunomedics shares, selling them after the news broke and Immunomedics’ stock price doubled.

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Merck's new antiviral molnupiravir (Quality Stock Arts / Shutterstock)

As Omi­cron spread looms, oral an­tivi­rals ap­pear to be one of the best de­fens­es — now we just need more

After South African scientists reported a new Covid-19 variant — dubbed Omicron by the WHO — scientists became concerned about how effective vaccines and monoclonal antibodies might be against it, which has more than 30 mutations in the spike protein.

“I think it is super worrisome,” Dartmouth professor and Adagio co-founder and CEO Tillman Gerngross told Endpoints News this weekend. Moderna CEO Stéphane Bancel echoed similar concerns, telling the Financial Times that experts warned him, “This is not going to be good.”

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Pfiz­er, Am­gen and Janssen seek fur­ther clar­i­ty on FDA's new ben­e­fit-risk guid­ance

Three top biopharma companies are seeking more details from the FDA on how the agency conducts its benefit-risk assessments for new drugs and biologics.

While Pfizer, Amgen and Janssen praised the agency for further spelling out its thinking on the subject in a new draft guidance, including a discussion of patient experience data as part of the assessment, the companies said the FDA could’ve included more specifics in the 20-page draft document.

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Janet Woodcock (AP Images)

Janet Wood­cock plots her fu­ture at FDA, with se­nior ad­vi­sor role to fall back on if Califf wins con­fir­ma­tion

Acting FDA commissioner Janet Woodcock has been the face of just about every drug approval decision at the agency since the turn of the century. Since the pandemic began, she’s moved between the top of the drugs center to the head of therapeutics at Operation Warp Speed, leading the drive for work on Covid-targeted mAbs and antivirals.

Looking forward — and pending a quick Senate confirmation to cement Rob Califf’s return to the top of FDA early next year — Woodcock’s role at the agency will again be in flux.

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Richard Pazdur (via AACR)

Ac­cel­er­at­ed ap­proval re­forms need mean­ing­ful con­fir­ma­to­ry tri­al im­prove­ments, pro­fes­sors write in Sci­ence

Outside of Covid-19, 2021 has been the year of the accelerated approval.

Beginning last spring, FDA openly challenged six “dangling” accelerated approvals (hadn’t confirmed their clinical benefit yet), three of which were later pulled by the companies.

Then in June, FDA pulled out the accelerated approval pathway, seemingly out of nowhere, to sign off on Biogen’s controversial Alzheimer’s drug Aduhelm. It hadn’t even been mentioned at the drug’s adcomm.

In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.

Lan Huang, BeyondSpring CEO

Months af­ter shock­ing in­vestors with lung can­cer win, Be­yond­Spring's lead drug hits road­block at the FDA

BeyondSpring shocked investors in early August after its once-marginal lead drug suddenly showed a lot of promise in a common form of lung cancer. With hopes high, the FDA has now slammed the door on that drug in another indication — does that spell bad news for BeyondSpring’s Cinderella story?

The FDA issued BeyondSpring a complete response letter for its plinabulin in combination with granulocyte colony-stimulating factor (G-CSF) for the prevention of chemotherapy-induced neutropenia, effectively shutting down the drug’s immediate chances at a marketing approval, the biotech said Wednesday.

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