Just days af­ter Bris­tol-My­ers Squibb man­aged to sur­prise the an­a­lyst brigade with a Phase III flop for its PD-1 check­point Op­di­vo com­bined with chemo in lung can­cer, Mer­ck’s dom­i­nant team is back with an­oth­er sol­id hit for a par­tic­u­lar­ly tough-to-treat sub­group of breast can­cer pa­tients.

Mer­ck’s Phase III KEYNOTE-522 tri­al con­nect­ed on one of two pri­ma­ry end­points, with their Keytru­da/chemo com­bo elim­i­nat­ing all signs of triple-neg­a­tive breast can­cer — what’s called a patho­log­i­cal com­plete re­sponse — at a sig­nif­i­cant­ly high­er rate than chemo alone, re­gard­less of PD-L1 lev­els in the neo-ad­ju­vant set­ting.

That’s an­oth­er first for Mer­ck, which has been steadi­ly rack­ing up new Phase III suc­cess­es for the mar­quee PD-1. In­ves­ti­ga­tors are con­tin­u­ing the tri­al as they wait to see how Keytru­da/chemo did on event-free sur­vival.

As usu­al, we’ll have to wait for a sci­en­tif­ic con­fer­ence to see the hard num­bers. But it’s im­por­tant to note that Mer­ck’s string of suc­cess­es with Keytru­da is al­so a psy­cho­log­i­cal vic­to­ry that can’t be un­der­es­ti­mat­ed. When Bris­tol-My­ers re­leased its lat­est batch of da­ta on Op­di­vo, the com­pa­ny al­so claimed a suc­cess on Part 1a of the Check­mate -227 tri­al, which met the co-pri­ma­ry end­point of OS, “demon­strat­ing a sta­tis­ti­cal­ly sig­nif­i­cant ben­e­fit for Op­di­vo plus low-dose Yer­voy (ip­il­i­mum­ab) ver­sus chemother­a­py in pa­tients whose tu­mors ex­press PD-L1 ≥1%.”

An­a­lysts weren’t hav­ing it, though, skep­ti­cal that the drug would beat Keytru­da af­ter see­ing the Keynote-189 da­ta. At this stage of the PD-1 bat­tle, Bris­tol-My­ers is as­sumed to come in be­hind Mer­ck.

The string of suc­cess­es has an­a­lysts com­pet­ing in peak sales fore­casts for Keytru­da. Mizuho’s Mara Gold­stein re­cent­ly not­ed:

News of the fail­ure of BMY’s Check­mate-227 Part 2, OP­DI­VO + chemother­a­py in front­line NSCLC to demon­strate an OS ben­e­fit vs. chemother­a­py alone, fur­ther so­lid­i­fies KEYTRU­DA’s dom­i­nance in this mul­ti-bil­lion dol­lar mar­ket op­por­tu­ni­ty, in our view, and is sup­port­ive of our in­vest­ment the­sis. We es­ti­mate that KEYTRU­DA sales will sur­pass $20 bil­lion by 2024, and that KEYTRU­DA will re­main the dom­i­nant check­point in­hibitor in the mar­ket.

Gold­stein added this morn­ing that every­thing is still look­ing rosy for Mer­ck as the com­pa­ny looks to add to its lead in triple neg­a­tive breast can­cer. Plus, the Eu­ro­peans are help­ing with an­oth­er pos­i­tive opin­ion for Mer­ck.

In ad­di­tion to TNBC, MRK al­so an­nounced a pos­i­tive CHMP opin­ion for KEYTRU­DA+IN­LY­TA in 1L RCC based on piv­otal Phase III KEYNOTE-426 da­ta – im­proved OS, PFS, and ORR vs SU­TENT. We think this lends sup­port to our view that KEYTRU­DA should pull far­ther ahead of com­peti­tors as the lead­ing check­point in­hibitor, and is sup­port­ive of our in­vest­ment the­sis.

So­cial im­age: Shut­ter­stock

When Regeneron scored an early approval for lipid lowering antibody Evkeeza back in February, the drugmaker cracked open a new pathway to lower abnormally high cholesterol levels. Now, Regeneron is chasing high triglycerides as well with some promising mid-stage data — but will genetic restrictions limit the drug’s use?

Regeneron’s Evkeeza (evinacumab) cut median triglyceride levels by more than 800 mg/dL (57%) in patients with a rare disorder causing abnormally high triglyceride levels compared with an overall increase of 50 mg/dL (1.8%) in participants on placebo, according to Phase II data presented Sunday at the virtual American College of Cardiology meeting.

AstraZeneca hasn’t seen many setbacks in recent months for SGLT2 inhibitor Farxiga, which broke ground in heart failure and kidney disease regardless of diabetes diagnosis. But the British drugmaker had to admit defeat in taking Farxiga into Covid-19, but follow-up results add a bit of a silver lining to that trial’s safety data.

Of hospitalized Covid-19 patients dosed with AstraZeneca’s Farxiga, 11.2% experienced an organ failure or died after 30 days of therapy compared with 13.8% of those given placebo, according to follow-up data from the DARE-19 study revealed Sunday at the virtual American College of Cardiology meeting.

Pfizer and Bristol Myers Squibb’s non-warfarin blood thinner Eliquis has raced out to become the most prescribed drug of its class on the market — even overtaking warfarin’s long-time lead. But in tricky-to-treat patients after a valve replacement, an investigator-sponsored study couldn’t turn up benefit and raised a troubling safety signal.

Eliquis failed to show benefit over standard of care in preventing serious clinical outcomes after a transaortic valve replacement (TAVR) and was linked to an “unexplained signal” in a subset of populations with a higher rate of non-CV deaths who did not need blood thinners apart from the surgery, according to data presented Saturday at the virtual American College of Cardiology meeting.

When Bristol Myers Squibb signed off on its $13 billion acquisition of MyoKardia back in October, it was making a big bet that lead drug mavacamten could prove a game changer in cardiac myopathy. Now, with the drug up for FDA review, Bristol Myers is backing up its case with new quality of life data.

Patients dosed with myosin inhibitor mavacamten posted a clinically significant increase in scores on the Kansas City Cardiomyopathy Questionnaire, a catch-all summary of symptoms and quality of life markers, over placebo at 30 weeks, according to data from the Phase III EXPLORER-HCM study presented Saturday at the virtual American College of Cardiology meeting.

If Novartis learned one thing from its interaction with the FDA over its latest heart failure approval for Entresto, it was that missing a primary endpoint may not be the nail in the coffin. Now, Entresto has missed again on a late-stage study in high-risk heart patients, and it’s already sowing the seeds for a path forward regardless.

Novartis’ Entresto couldn’t best standard-of-care ramipril in staving off a composite of deaths and heart failure events in patients with left ventricular systolic dysfunction and/or pulmonary congestion who have had a prior heart attack, according to topline data from the Phase III PARADISE-MI study revealed Saturday at the virtual American College of Cardiology meeting.