Roger Perlmutter, Merck

Catch­ing up with Roche, Mer­ck racks up pos­i­tive da­ta in front­line triple neg­a­tive breast can­cer

Mer­ck’s Keytru­da may not have qual­i­fied as a sec­ond- or third-line treat­ment of triple neg­a­tive breast can­cer, but the PD-1 in­hibitor is show­ing promise for the first-line set­ting in a Phase III tri­al.

In­ves­ti­ga­tors for the KEYNOTE-355 study re­port that Keytru­da plus chemother­a­py sig­nif­i­cant­ly im­proved pro­gres­sion-free sur­vival for pa­tients with metasta­t­ic TNBC whose tu­mors ex­press PD-L1 com­pared to chemo alone, hit­ting a co-pri­ma­ry end­point.

The topline re­sult was from an in­ter­im analy­sis. The oth­er pri­ma­ry end­point, over­all sur­vival, is still be­ing eval­u­at­ed.

Front­line triple neg­a­tive breast can­cer — a par­tic­u­lar­ly hard to treat form of the dis­ease that ac­counts for 10% to 20% of all breast can­cer cas­es — is 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. Tecen­triq is ap­proved in com­bi­na­tion with Abrax­ane for this in­di­ca­tion.

It didn’t help when Mer­ck con­ced­ed fail­ure in KEYNOTE-119, where Keytru­da failed to help pre­vi­ous­ly treat­ed pa­tients live longer.

But things soon took a turn for the bet­ter, as the com­pa­ny found that a neoad­ju­vant reg­i­men of Keytru­da and chemo — fol­lowed by Keytru­da monother­a­py af­ter surgery — in­duced a high­er patho­log­i­cal com­plete re­sponse rate. The con­trol arm, which re­ceived chemo alone, saw a pCR of 51.2% ver­sus 64.8% for the Keytru­da group.

That’s a key mark­er for pro­gres­sion and re­cur­rence, ex­ecs said.

But SVB Leerink an­a­lysts are less op­ti­mistic. In a note, Daina Gray­bosch point­ed out that the tri­al had six pri­ma­ry end­points, not all of which ap­peared to have been met. On­ly pa­tients with PD-L1 Com­bined Pos­i­tive Score (CPS) ≥ 10 ben­e­fit­ed, but not those whose CPS was high­er than or equal to 1.

Though they re­port­ed pos­i­tive topline da­ta for Keytru­da (pem­brolizum­ab) with chemother­a­py in PD-L1 high pa­tients, the reg­i­men failed to show ben­e­fit in a broad­er TNBC pop­u­la­tion. By the time Mer­ck en­ters the mar­ket, Roche will have a two-year lead, in ad­di­tion to a more pre­dic­tive bio­mark­er for clin­i­cal ben­e­fit (im­mune-cell (IC) PD-L1). A launch for Keytru­da in neo-ad­ju­vant TNBC would mit­i­gate this mar­ket risk, but we do not ex­pect this un­til 2021 at the ear­li­est, await­ing more ma­ture dis­ease-free sur­vival da­ta.

Roger Perl­mut­ter, who over­sees Keytru­da’s ex­pan­sive de­vel­op­ment pro­gram, high­light­ed that tri­al — KEYNOTE-522 — to­geth­er with the new Phase III as he talked up the po­ten­tial of reg­is­tra­tion.

While tar­get­ed ther­a­pies have ben­e­fit­ed a num­ber of breast can­cer pa­tients, the fact that TNBC is nei­ther fu­eled by the hor­mones es­tro­gen and prog­es­terone nor by the HER2 pro­tein ren­ders it es­pe­cial­ly hard to treat.

“While de­tail da­ta has yet to be an­nounced, a PFS hit in this pop­u­la­tion is im­por­tant giv­en the lack of avail­able ther­a­pies in this dis­ease, and fur­ther in­di­cates a role of check­point in­hibitors in a sub­set (of) TNBC pa­tients,” Mara Gold­stein of Mizuho not­ed about KEYNOTE-355.

Roche is look­ing to ex­pand its suc­cess with the Tecen­triq and Abrax­ane reg­i­men by adding their PI3K/AKT path­way drug ipatasert­ib to the mix — with some en­cour­ag­ing ear­ly da­ta.

Oth­er small­er play­ers have ze­roed in on new tar­gets, such as pro­tein ki­nase C, Lipocalin 2 and CD24.

Ryan Watts, Denali CEO

Bio­gen hands De­nali $1B-plus in cash, $1B-plus in mile­stones to part­ner on late-stage Parkin­son’s drug

Biogen is handing over more than a billion dollars cash to partner with the up-and-coming neurosciences crew at Denali on a new therapy for Parkinson’s. And the big biotech is ready to pile on more than a billion dollars more in milestones — if the alliance is a success.

For Biogen $BIIB, the move on Denali’s small molecule inhibitors of LRRK2 puts them in line to collaborate on a late-stage program for DNL151, which is scheduled to start next year.

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Covid-19 roundup: J&J and BAR­DA agree to $1 bil­lion for 100 mil­lion dos­es; Plas­ma re­duces mor­tal­i­ty by 50% — re­ports

J&J has become the latest vaccine developer to agree to supply BARDA with doses of their Covid-19 vaccine, signing an agreement that will give the government 100 million doses in exchange for $1 billion in funding.

The agreement, similar to those signed by Novavax, Sanofi and AstraZeneca-Oxford, provides funding not only for individual doses but to help J&J ramp up manufacturing. Pfizer, by contrast, received $1.95 billion for the doses alone. Still, if one looked at each agreement as purchase amounts, J&J’s deal would be $10 per dose, slotting in between Novavax’s $16 per dose and AstraZeneca’s $4 per dose.

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Douglas Fambrough, Dicerna CEO (Boehringer Ingelheim via YouTube)

Roche-backed Dicer­na push­es in­to the pack rac­ing to­ward the block­buster hep B goal line, armed with PhI da­ta

Dicerna has lined up a set of proof-of-concept data from a small cohort of hepatitis B patients in a match-up against some heavyweight rivals which got out in front of this race. And right in the front row you’ll find a team from Roche, which paid $200 million in cash and offered another $1.5 billion in milestones to partner with Dicerna $DRNA on their RNAi program for hep B.

Right now it’s looking competitive, with lots of big challenges ahead.

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Ben Dake (Source: Aerovate)

RA Cap­i­tal-backed Aerovate launch­es with $72.6M to treat PAH with a re­pur­posed can­cer med

The landmark cancer drug imatinib has been on the market since 2001, first sold by Novartis as Gleevec and in recent years as a generic. Now, a new Boston biotech is aiming to repurpose the drug as a treatment for pulmonary arterial hypertension.

Aerovate emerged from stealth Thursday and announced a $72.6 million Series A, which will be used to develop and run trials for its candidate AV-101 — a dry powder version of imatinib meant to be used with an inhaler. The company emerged from RA Capital’s incubator and funding was led by Sofinnova.

Ab­b­Vie aban­dons a pi­o­neer­ing CRISPR R&D al­liance with Ed­i­tas as Brent Saun­der­s' deal is cast out

A little more than 3 years ago Allergan paid $90 million in a cash upfront to partner with gene editing player Editas on a CRISPR alliance focused on the eye. The lead program centered on LCA10, a rare, inherited retinal degenerative disease that appears in childhood and leads to blindness.

Allergan then went to AbbVie $ABBV in a buyout, and the pharma giant has no interest in moving forward on the gene editing front. The company punted it all back to Editas Thursday, with the biotech $EDIT noting in a statement after the market closed Thursday that it is regaining all rights for its ocular medicines, including EDIT-101.

President Trump speaks with members of the media before boarding Marine One (AP Images)

'Oc­to­ber is com­ing,' and every­one still wants to know if a Covid-19 vac­cine will be whisked through the FDA ahead of the elec­tion

Right on the heels of a lengthy assurance from FDA commissioner Stephen Hahn that the agency will not rush through a quick approval for a Covid-19 vaccine, the President of the United States has some thoughts on timing he’d like to share.

In an exchange with Fox News’ Geraldo Rivera on Thursday, President Trump allowed that a vaccine could be ready to roll “sooner than the end of the year, could be much sooner.”

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Jan Hatzius (Photographer: Christopher Goodney/Bloomberg via Getty Images)

When will it end? Gold­man econ­o­mist gives late-stage vac­cines a good shot at tar­get­ing 'large shares' of the US by mid-2021 — but the down­side is daunt­ing

It took decades for hepatitis B research to deliver a slate of late-stage candidates capable of reining the disease in.

With Covid-19, the same timeline has devoured all of 5 months. And the outcome will influence the lives of billions of people and a multitrillion-dollar world economy.

Count the economists at Goldman Sachs as optimistic that at least one of these leading vaccines will stay on this furiously accelerated pace and get over the regulatory goal line before the end of this year, with a shot at several more near-term OKs. That in turn should lead to the production of billions of doses of vaccines that can create herd immunity in the US by the middle of next year, with Europe following a few months later.

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J&J gets a fresh OK for es­ke­t­a­mine, but is it re­al­ly the game-chang­er for de­pres­sion Trump keeps tweet­ing about?

Backed by an enthusiastic set of tweets from President Trump and a landmark OK for depression, J&J scooped up a new approval from the FDA for Spravato today. But this latest advance will likely bring fresh scrutiny to a drug that’s spurred some serious questions about the data, as well as the price.

First, the approval.

Regulators stamped their OK on the use of Spravato — developed as esketamine, a nasal spray version of the party drug Special K or ketamine — for patients suffering from major depressive disorder with acute suicidal ideation or behavior.

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Le­vo Ther­a­peu­tics miss­es pri­ma­ry end­point in PhI­II tri­al of Prad­er-Willi drug — the lat­est set­back in a dis­as­ter-prone field

Marking yet another setback in the Prader-Willi Syndrome field, Levo Therapeutics failed to hit its primary endpoint in a Phase III study of intranasal carbetocin. But the biotech is now shifting its focus to the secondary endpoints in an effort to pluck victory out of the jaws of defeat.

The disorder, characterized by a false sense of starvation, is caused by the absence or deletion of a father’s chromosome 15. Illinois-based Levo’s potential therapy involves a selective oxytocin-receptor agonist.