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.

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Dipal Doshi, Entrada Therapeutics CEO

Ver­tex just found the next big ‘trans­for­ma­tive’ thing for the pipeline — at a biotech just down the street

Back in the summer of 2019, when I was covering Vertex’s executive chairman Jeff Leiden’s plans for the pipeline, I picked up on a distinct focus on myotonic dystrophy Type I, or DM1 — one of what Leiden called “two diseases (with DMD) we’re interested in and we continue to look for those assets.”

Today, Leiden’s successor at the helm of Vertex, CEO Reshma Kewalramani, is plunking down $250 million in cash to go the extra mile on DM1. The lion’s share of that is for the upfront, with a small reserve for equity in a deal that lines Vertex up with a neighbor in Seaport that has been rather quietly going at both of Vertex’s early disease targets with preclinical assets.

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Ab­b­Vie slapped with age dis­crim­i­na­tion law­suit, fol­low­ing oth­er phar­mas

Add AbbVie to the list of pharma companies currently facing age discrimination allegations.

Pennsylvania resident Thomas Hesch filed suit against AbbVie on Wednesday, accusing the company of passing him over for promotions in favor of younger candidates.

Despite 30 years of pharma experience, “Hesch has consistently seen younger, less qualified employees promoted over him,” the complaint states.

Rami Elghandour, Arcellx CEO

Up­dat­ed: Gilead, Ar­cel­lx team up on an­ti-BC­MA CAR-T as biotech touts a 100% re­sponse rate at #ASH22

Gilead and Kite are plunking down big cash to get into the anti-BCMA CAR-T game.

The pair will shell out $225 million in cash upfront and $100 million in equity to Arcellx, Kite announced Friday morning, to develop the biotech’s lead CAR-T program together. Kite will handle commercialization and co-development with Arcellx, and profits in the US will be split 50-50.

Concurrent with the deal, Arcellx revealed its latest cut of data for the program known as CART-ddBCMA, ahead of a full presentation at this weekend’s ASH conference — a 100% response rate among patients getting the therapy. Investors jumped at the dual announcements, sending Arcellx shares $ACLX up more than 25% in Friday’s morning session.

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Christian Itin, Autolus CEO (UKBIO19)

Au­to­lus tips its hand, bags $220M as CAR-T show­down with Gilead looms

The first batch of pivotal data on Autolus Therapeutics’ CAR-T is in, and execs are ready to plot a path to market.

With an overall remission rate of 70% at the interim analysis featuring 50 patients, the results set the stage for a BLA filing by the end of 2023, said CEO Christian Itin.

Perhaps more importantly — given that Autolus’ drug, obe-cel, is going after an indication that Gilead’s Tecartus is already approved for — the biotech highlighted “encouraging safety data” in the trial, with a low percentage of patients experiencing severe immune responses.

David Light, Valisure CEO

Val­isure in the hot seat: New Form 483 over a 2021 in­spec­tion as CEO fires back

The notorious drug testing company Valisure, which has made a name for itself by forcing FDA’s hand with some of its safety-related uncoverings, received a letter this week after the FDA uncovered violations at its Connecticut-based testing lab in 2021.

The letter, which was sent on Dec. 5, stated that the FDA is “concerned” that Valisure was not aware of  drug supply chain security requirements.

Mark Cuban (Jed Jacobsohn/AP Images)

Mov­ing to the em­ploy­er side of health­care, Mark Cuban's Cost Plus Drugs part­ners with a PBM

From “Shark Tank” to direct-to-consumer generic drugs, Mark Cuban has made another inroad in the ongoing battle over prescription drug prices. His cost-plus-15% generic drug company, frequently undercutting many competitors, now has its sights set on the employer healthcare market.

Cost Plus Drugs, which originally pledged to cut out PBMs, has now partnered with the PBM EmsanaRx, majority owned by the Purchaser Business Group on Health, to launch a supplemental drug discount program designed specifically for self-funded employers, the company announced Thursday.

WIB22: Am­ber Salz­man had few op­tions when her son was di­ag­nosed with a rare ge­net­ic dis­ease. So she cre­at­ed a bet­ter one

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

Amber Salzman’s life changed on a cold, damp day in Paris over tiny plastic cups of lukewarm tea.

She was meeting with Patrick Aubourg, a French neurologist studying adrenoleukodystrophy, or ALD, a rare genetic condition that causes rapid neurological decline in young boys. It’s a sinister disease that often leads to disability or death within just a few years. Salzman’s nephew was diagnosed at just 6 or 7 years old, and died at the age of 12.

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Ahead of ad­comm, FDA rais­es un­cer­tain­ties on ben­e­fit-risk pro­file of Cy­to­ki­net­ic­s' po­ten­tial heart drug

The FDA’s Cardiovascular and Renal Drugs Advisory Committee will meet next Tuesday to discuss whether Cytokinetics’ potential heart drug can safely reduce the risk of cardiovascular death and heart failure in patients with symptomatic chronic heart failure with reduced ejection fraction.

The drug, known as omecamtiv mecarbil and in development for more than 15 years, has seen mixed results, with a first Phase III readout from November 2020 hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as key to breaking into the market.