Mer­ck­'s Keytru­da nets an­oth­er ap­proval, this time in triple neg­a­tive breast can­cer. Can it catch up to Tecen­triq?

An­oth­er day, an­oth­er win for Mer­ck’s block­buster Keytru­da.

The FDA has grant­ed ac­cel­er­at­ed ap­proval for the cash cow com­bined with chemother­a­py in triple neg­a­tive breast can­cer, giv­ing the drug the green light in its 18th dif­fer­ent can­cer. Mon­day’s new in­di­ca­tion comes for pa­tients with PD-L1-ex­press­ing tu­mors with a Com­bined Pos­i­tive Score of at least 10.

Mer­ck not­ed that due to the na­ture of the ac­cel­er­at­ed ap­proval, the thumbs up is con­tin­gent up­on con­fir­ma­to­ry tri­als.

Da­ta for the ap­proval first came back in Feb­ru­ary, when the Keynote-355 tri­al demon­strat­ed Keytru­da plus chemo sig­nif­i­cant­ly im­proved pro­gres­sion-free sur­vival com­pared to chemo by it­self. The study showed that, in the tar­get pop­u­la­tion with a CPS of at least 10, the com­bi­na­tion re­duced the risk of dis­ease pro­gres­sion or death by 35% with a me­di­an PFS of 9.7 months, against 5.6 months in the place­bo arm.

On safe­ty, the Feb­ru­ary da­ta showed 2.5% of all pa­tients in the drug arm saw fa­tal ad­verse events, in­clud­ing car­diac ar­rest and sep­tic shock, with se­ri­ous side ef­fects ap­pear­ing in 30% of pa­tients. Keytru­da was dis­con­tin­ued due to ad­verse events in 11% of pa­tients.

Front­line triple neg­a­tive breast can­cer is a par­tic­u­lar­ly dif­fi­cult in­di­ca­tion to treat, as the growth of the can­cer is not fu­eled by the hor­mones es­tro­gen and prog­es­terone, or by the HER2 pro­tein. It’s one of the rare fields in which Roche’s PD-L1 Tecen­triq has en­joyed a head start over Keytru­da and Op­di­vo, the lead­ers in the check­point race, as Tecen­triq is ap­proved in com­bi­na­tion with Abrax­ane for this in­di­ca­tion.

Back in May 2019, Mer­ck con­ced­ed a fail­ure in the are­na af­ter a Phase III study flopped on over­all sur­vival. But a few months lat­er, the phar­ma turned things around af­ter dis­cov­er­ing a neoad­ju­vant reg­i­men of Keytru­da and chemo — fol­lowed by Keytru­da monother­a­py af­ter surgery — in­duced a high­er patho­log­i­cal com­plete re­sponse rate.

Though ex­ecs pre­sent­ed that as a pos­i­tive, some an­a­lysts didn’t paint as sun­ny a pic­ture. This past Feb­ru­ary, when the Keynote-355 topline da­ta was first pub­lished, SVB Leerink’s Daina Gray­bosch point­ed out that be­cause on­ly pa­tients with a CPS of at least 10 ap­peared to ben­e­fit, in­stead of a score of at least 1, it won’t be able to treat as broad a pop­u­la­tion as Tecen­triq. Roche, she not­ed, al­so has about a two-year head start.

A Mer­ck spokesper­son al­so had this to say about the CPS and IC per­cent­ages:

In TNBC, we mea­sure PD-L1 with a com­bined pos­i­tive score (CPS). The CPS in­cludes stain­ing for tu­mor cells, as well as tu­mor-in­fil­trat­ing im­mune cells and it is not a per­cent­age. We be­lieve CPS ≥10 is rough­ly equiv­a­lent to how Roche scores PD-L1+ pa­tients (IC>=1% based on the SP142 as­say) on tu­mor-in­fil­trat­ing im­mune cells (IC). The preva­lence of the PD-L1 pos­i­tive pop­u­la­tion in TNBC whether by CPS of greater than or equal to 10 or IC of 1% is both about 40%.

Keytru­da is al­ready one of the best-sell­ing drugs in the world, hav­ing notched rough­ly $3.9 bil­lion in the first half of 2020 alone. Some have pre­dict­ed the drug may over­take Ab­b­Vie’s Hu­mi­ra as the top sell­er with­in the next few years, with the most op­ti­mistic es­ti­mate pegged for $22.2 bil­lion in sales by 2025.

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.

Stéphane Bancel, Moderna CEO

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Even as public health officials remain guarded about their comments on the likelihood Omicron will escape the reach of the currently approved Covid-19 vaccines, there’s growing scientific consensus that we’re facing a variant that threatens to overwhelm the vaccine barricades that have been erected.

Stéphane Bancel, the CEO of Moderna, one of the leading mRNA players whose quick vault into the markets with a highly effective vaccine created an instant multibillion-dollar market, added his voice to the rising chorus early Tuesday. According to Bancel, there will be a significant drop in efficacy when the average immune system is confronted by Omicron. The only question now is: How much?

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Ap­peals court puts the fi­nal nail in the cof­fin for Tec­fidera patent, adding to Bio­gen's bur­geon­ing set­backs

In another setback for Biogen, the big biotech lost its appeal to revive a patent for the once-blockbuster drug Tecfidera, marking a likely conclusion to the case.

The US Court of Appeals for the Federal Circuit issued the ruling Tuesday morning, saying Biogen failed to satisfy the “written description” requirement for patent law. As a result, Mylan-turned-Viatris will be able to sell its multiple sclerosis generic without fear of infringement and Biogen will have to find a new revenue driver elsewhere.

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Glax­o­SmithK­line poach­es Pfiz­er's vi­ral vac­cines lead in rush to cap­i­tal­ize on fu­ture of mR­NA

GlaxoSmithKline has appointed Philip Dormitzer, formerly chief scientific officer of Pfizer’s viral vaccines unit, as its newest global head of vaccines R&D, looking to leverage one of the leading minds behind Pfizer and BioNTech’s RNA collaboration that led to Covid-19 jab Comirnaty, the British drug giant said Tuesday.

Dormitzer had been with Pfizer for a little more than six years, joining up after a seven-year stint with Novartis, where he reached the role of US head of research and head of global virology for the company’s vaccines and diagnostics unit.

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In­tro­duc­ing End­points Stu­dio, a new way to ad­ver­tise with End­points-craft­ed brand­ing cam­paigns

Since our start in 2016, Endpoints has grown fast while executing our mission to cover biopharma’s most critical developments for industry pros worldwide. As readership has grown, our advertising business has too. Endpoints advertising partners support the mission and engage their desired audiences through announcements on our email and web platforms, brand recognition in our event coverage and sponsorships of Endpoints daily and weekly reports.

FDA can­cels ODAC meet­ing this week to re­view two more dan­gling ac­cel­er­at­ed ap­provals — but won't ex­plain why

The FDA’s Oncologic Drugs Advisory Committee has decided to cancel a planned meeting on Thursday to discuss two cancer drugs that previously won accelerated approvals but failed to confirm clinical benefit in required follow-up trials or have taken a long time to finish those trials.

The FDA said in a statement that the meeting “is no longer needed” but did not offer further detail on why exactly it was canceled, telling Endpoints News to contact the companies. Attempts to contact both Secura Bio and Acrotech went unreturned. The companies may have decided to pull these treatments from the market, or they’ve come to new agreements with the agency on their confirmatory trials.

How to use reg­istry da­ta to sup­port FDA de­ci­sion mak­ing: Agency ex­plains in new guid­ance

Drugmakers looking to design a new registry or use an existing one to support a regulatory decision on a drug’s effectiveness or safety will need to consult with a new draft guidance released Monday by the FDA.

The agency’s reliance on registry data for regulatory decisions dates back more than two decades, at least, as in 1998 Bayer won approval for its anticoagulant Refludan (withdrawn from the market in 2013 for commercial reasons) based in part on a historical control group pulled from a registry.

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Till­man Gern­gross on Omi­cron: 'It is a grim sit­u­a­tion...we’re go­ing to see a sig­nif­i­cant drop in vac­cine ef­fi­ca­cy'

Tillman Gerngross, the rarely shy Dartmouth professor, biotech entrepreneur and antibody expert, has been warning for over a year that the virus behind Covid-19 would likely continue to mutate, potentially in ways that avoid immunity from infection and the best defenses scientists developed. He spun out a company, Adagio, to build a universal antibody, one that could snuff out any potential mutation.

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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.