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.

Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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In his­toric Covid-19 ad­comm, vac­cine ex­perts de­bate a sea of ques­tions — but of­fer no clear an­swers

The most widely anticipated and perhaps most widely watched meeting in the FDA’s 113-year history ended late Thursday night with a score of questions and very few answers.

For nearly 9 hours, 18 different outside experts listened to public health agencies and foundations present how the United States’ Covid-19 vaccine program developed through October, and they debated where it should go from there: Were companies testing the right metrics in their massive trials? How long should they track patients before declaring a vaccine safe or effective? Should a vaccine, once authorized, be given to the volunteers in the placebo arm of a trial?

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A top drug pro­gram at Bay­er clears a high bar for CKD — open­ing the door to an FDA pitch

Over the past 4 years, Bayer has been steering a major trial through a pivotal program to see if their drug finerenone could slow down the pace of chronic kidney disease in patients suffering from both CKD as well as Type 2 diabetes.

Today, their team jumped on a virtual meeting hosted by the American Society of Nephrology to offer a solid set of pivotal data to demonstrate that the drug can delay dialysis or a kidney replacement as well as cardio disease, while also adding some worrying signs of hyperkalemia among the patients taking the drug. And they’re hustling it straight to regulators in search of an approval for kidney disease and cardio patients — one of the toughest challenges in the book, as demonstrated by repeated past failures.

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Biond­Vax stock im­plodes af­ter a big PhI­II gam­ble for its uni­ver­sal flu vac­cine fails

After flying high on Wall Street for the last few months of a pandemic, BiondVax’s stock and dreams of getting approval for its universal flu vaccine hit the windshield.

The Jerusalem-based biotech announced on Friday that its only clinical candidate, M-001, failed both primary and secondary endpoints in a Phase III study. There was no statistically significant difference in reduction of flu illness and severity between the vaccine and placebo groups, according to the company. The vaccine did prove safe, if ineffective, BiondVax said.

Pascal Soriot, AstraZeneca CEO (Zach Gibson/Bloomberg via Getty Images)

UP­DAT­ED: FDA gives As­traZeneca the thumbs-up to restart PhI­II Covid-19 vac­cine tri­als, and J&J is prepar­ing to re­sume its study

Several countries had restarted their portions of AstraZeneca’s global Phase III Covid-19 vaccine trial after the study was paused worldwide in early September, but the US notably stayed on the sidelines — until now. Friday afternoon the pharma giant announced the all clear from US regulators. And on top of that, J&J announced Friday evening that it’s preparing to resume its own Phase III vaccine trial.

Ul­tragenyx in­jects $40M to grab Solid's mi­crody­s­trophin trans­gene — while side­step­ping the AAV9 vec­tor that stirred up safe­ty fears

Since before Ilan Ganot started Solid Bio to develop a gene therapy for kids like his son, who has Duchenne muscular dystrophy, Ultragenyx CEO Emil Kakkis has been watching and advising the former investment banker as he navigated the deep waters of drug development.

Just as Solid is getting back up on its feet after a yearlong clinical hold, Kakkis has decided to jump in for a formal alliance.

With a $40 million upfront, Ultragenyx is grabbing 14.45% of Solid’s shares $SLDB and the rights to its microdystrophin construct for use in combination with AAV8 vectors. Solid’s lead program, which utilizes AAV9, remains unaffected. The company also retains rights to other applications of its transgene.

Dan O'Day, Gilead CEO (Andrew Harnik, AP Images)

UP­DAT­ED: FDA anoints Gilead­'s remde­sivir as the Covid-19 treat­ment win­ner, hand­ing down full ap­proval — de­spite some deep skep­ti­cism

Seven months into the Covid-19 pandemic, the race to develop a treatment for the disease that’s proved to be the biggest health crisis in a century has an officially designated winner: Gilead. And they’re picking up the prize — worth billions in peak sales — despite a major study that concluded the drug was no help in reducing the number of people who die from the virus.

The FDA handed down a thumbs-up for remdesivir, the company announced Thursday afternoon, as the drug becomes the first fully approved treatment for Covid-19 in the US. Remdesivir, to be marketed as Veklury, will come with a label for treatment in adults and children older than 12 in Covid-19 cases that require hospitalization.

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Adam Koppel and Jeffrey Schwartz, Bain

Bain ex­ecs Adam Kop­pel and Jef­frey Schwartz line up $125M for their first blank check deal as Wall Street con­tin­ues to em­brace biotech

Adam Koppel and Jeffrey Schwartz have jumped into the blank check game, raising $125 million for a stock listing in search of a company.

Their SPAC, BCLS Acquisition Corp, raised $125 million this week, with a line on $25 million more as it scouts for a biotech in search of money and a place on Wall Street.

The two principals at Bain Life Sciences have been on a romp since they set up the Bain operation 4 years ago. Their S-1 spells out a track record of 22 deals totaling $650 million for the life sciences group, which led to 9 IPOs.

Covid-19 roundup: An mR­NA play­er gets a boost out of the lat­est round of an­i­mal da­ta; Phase­Bio pulls the plug on treat­ment tri­al

The big tell for CureVac $CVAC is coming up with a looming early-stage readout on their mRNA Covid-19 vaccine in the clinic. But for now they’ll make do with an upbeat assessment on the preclinical animal data they used to get into the clinic.

Researchers for the German biotech say they got the high antibody titers and T cell activation they were looking for, lining up a hamster challenge to demonstrate — in a simple model — that the vaccine could protect the furry creatures. Like the other mRNA vaccines, the drug sends instructions to spur cells to decorate themselves with the distinctive spike on the virus to elicit an immune response.