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.

Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Steve Cutler, Icon CEO (Icon)

In the biggest CRO takeover in years, Icon doles out $12B for PRA Health Sci­ences to fo­cus on de­cen­tral­ized clin­i­cal work

Contract research M&A had a healthy run in recent years before recently petering out. But with the market ripe for a big buyout and the Covid-19 pandemic emphasizing the importance of decentralized trials, Wednesday saw a tectonic shift in the CRO world.

Icon, the Dublin-based CRO, will acquire PRA Health Sciences for $12 billion in a move that will shake up the highest rungs of a fragmented market. The merger would combine the 5th- and 6th-largest CROs by 2020 revenue, according to Icon, and the merger will set the newco up to be the second-largest global CRO behind only IQVIA.

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Tom Barnes (Orna)

The mR­NA era is here. MPM be­lieves the fu­ture be­longs to oR­NA — and Big Phar­ma wants a seat at the ta­ble

If the ultra-fast clinical development of Covid-19 vaccines opened the world’s eyes to the promises of messenger RNA, the subsequent delays in supply offered a crash course on the ultra-complex process of producing them. Even before the formulation and fill-finish steps, mRNA is the precious end product from an arduous journey involving enzyme-aided transcription, modification and purification.

For Bristol Myers Squibb, Novartis Institutes for Biomedical Research, Gilead’s Kite and Astellas, it’s time to rethink the way therapeutic RNA is engineered.

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S&P ex­pects steady ero­sion in Big Phar­ma's cred­it pro­file in 2021 as new M&A deals roll in — but don't un­der­es­ti­mate their un­der­ly­ing strength

S&P Global has taken a look at the dominant forces shaping the pharma market and come to the conclusion that there will be more downgrades than upgrades in 2021 — the 8th straight year of steady decline.

But it’s not all bad news. Some things are looking up, and there’s still plenty of money to be made in an industry that enjoys a 30% to 40% profit margin, once you factor in steep R&D expenses.

Tal Zaks, Moderna CMO (AP Photo/Rodrique Ngowi, via still image from video)

CMO Tal Zaks bids Mod­er­na a sur­prise adieu as biotech projects $18.4B in rev­enue, plots post-Covid ex­pan­sion

How do you exit a company after six years in style? Developing one of the most lucrative and life-saving products in pharma history is probably not the worst way to go.

Tal Zaks, Moderna’s CMO since 2015, will leave the mRNA biotech in September, the biotech disclosed in their annual report this morning. The company has already retained the recruitment firm Russell Reynolds to find a replacement.

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FDA re­view­ers en­dorse J&J sin­gle-dose shot, lay­ing path for 3rd US vac­cine

J&J’s single-dose vaccine may not have produced quite the stellar numbers of the mRNA shots, but it still won a ringing endorsement from FDA reviewers, who argued in briefing documents that it could provide robust protection against the still-raging virus.

The FDA confirmed that across just under 40,000 volunteers, the vaccine proved 66% effective at preventing symptomatic Covid-19, including 72% effective in the United States. Although that’s short of the 95% figures put up by Moderna and Pfizer-BioNTech, the shot was still 85% effective at stopping severe disease 28 days after administration. There were seven deaths in the placebo group — zero in the vaccine group.

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Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

UP­DAT­ED: Mer­ck takes a swing at the IL-2 puz­zle­box with a $1.85B play for buzzy Pan­dion and its au­toim­mune hope­fuls

When Roger Perlmutter bid farewell to Merck late last year, the drugmaker perhaps best known now for sales giant Keytruda signaled its intent to take a swing at early-stage novelty with the appointment of discovery head Dean Li. Now, Merck is signing a decent-sized check to bring an IL-2 moonshot into the fold.

Merck will shell out roughly $1.85 billion for Pandion Pharmaceuticals, a biotech hoping to gin up regulatory T cells (Tregs) to treat a range of autoimmune disorders, the drugmaker said Thursday.

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Biden is look­ing be­yond Wood­cock or Sharf­stein for FDA com­mis­sion­er — re­port

Neither Janet Woodcock nor Joshua Sharfstein is likely to be nominated as the permanent FDA commissioner, Steve Usdin at BioCentury reports.

The White House is looking for alternatives to Woodcock, the acting chief and longtime CDER director, after opposition from several Democratic senators who are calling on others to block her nomination if her name is put forth, according to Usdin. Sharfstein, the former principal deputy FDA commissioner and current Johns Hopkins professor, is out of the running altogether.