Mer­ck and Bay­er un­veil the da­ta be­hind their CV ‘suc­cess,’ un­der­whelm­ing the in­dus­try

Four months af­ter Mer­ck an­nounced a sur­prise Phase III suc­cess on the heart drug they gave Bay­er $1 bil­lion for, the full da­ta is out — and car­di­ol­o­gists, in­vestors and pay­ers are left won­der­ing just how ef­fec­tive the drug re­al­ly is.

The da­ta, pub­lished in the New Eng­land Jour­nal of Med­i­cine and an­nounced in the vir­tu­al Amer­i­can Col­lege of Car­di­ol­o­gy meet­ing, showed that across 5,050 pa­tients, veri­ciguat led to a 10% re­duc­tion in hos­pi­tal­iza­tions for heart fail­ure. Al­though that met the pri­ma­ry end­point — the com­pos­ite of time un­til first death or hos­pi­tal­iza­tion for heart fail­ure — it un­der­whelmed, par­tic­u­lar­ly as the drug did not lead to a sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tion in death.

The No­vem­ber an­nounce­ment had left it up in the air if the com­pos­ite suc­cess had been fu­eled by re­duc­tions in hos­pi­tal­iza­tions, or re­duc­tions in death, or both. That an­nounce­ment had sur­prised some, giv­en that the drug failed Phase II tri­als.

“Our KOLs’ mod­est ex­pec­ta­tions were met if not missed and in­vestor ex­pec­ta­tions were def­i­nite­ly missed,” Cowen’s Steve Scala wrote in a note, cit­ing a sur­vey they had done at their in­vestor con­fer­ence ear­li­er this month. He pro­ject­ed $500 mil­lion in peak sales in 2025.

In ad­vance of the vir­tu­al con­fer­ence, SVB Leerink’s Daina Gray­bosch not­ed that the car­dio­vas­cu­lar mar­ket had be­come murky in re­cent years. She cit­ed No­var­tis’s En­tresto, a drug that’s been slow to reach pa­tients de­spite be­ing hailed as a ma­jor ad­vance in car­dio­vas­cu­lar ther­a­py, and point­ed to an ob­sta­cle course of re­luc­tant pay­ers, un­fa­mil­iar physi­cians, out-of-pock­et costs for pa­tients and loom­ing ques­tions about re­al-world ben­e­fits. Still, with the po­ten­tial for re­al-world da­ta, she said the da­ta could Mer­ck might get “a leg up” on the mar­ket.

In­stead, on Mon­day, she wrote the da­ta re­duced veri­ciguat’s po­ten­tial to a “niche” mar­ket in those who can’t tol­er­ate parts of the cur­rent stan­dard-of-care. Even that, though, was based on da­ta not yet re­leased, in­clud­ing qual­i­ty of life met­rics in a larg­er set of pa­tients al­so treat­ed with En­tresto.

“MEDA­Corp car­di­ol­o­gists we spoke with were pleased to have an ad­di­tion­al ther­a­peu­tic op­tion at their dis­pos­al, with pos­i­tive (but not en­thu­si­as­tic) com­men­tary pro­vid­ed on veri­ciguat’s in­cre­men­tal ben­e­fit,” Gray­bosch wrote, cit­ing Leerink’s ex­pert net­work.

Car­di­ol­o­gists who have may have or­di­nar­i­ly de­bat­ed the re­sults in the hall­ways of a Chica­go ho­tel in­stead dis­cussed them on Twit­ter, with some prais­ing the hos­pi­tal­iza­tion ben­e­fit and not­ing that, while not sta­tis­ti­cal­ly sig­nif­i­cant, the tri­al did see an ab­solute de­cline in deaths. Oth­ers de­scribed the com­pos­ite win as “am­bigu­ous.”

In a we­b­cast for the Amer­i­can Jour­nal of Man­aged Care, Uni­ver­si­ty of Mis­sis­sip­pi Col­lege of Med­i­cine chair Javed But­ler said the re­sults looked more promis­ing when you con­sid­ered how short the fol­low-up was and the par­tic­u­lar­ly high-risk pa­tient pop­u­la­tion.

“So, if you ac­tu­al­ly look at the ab­solute risk re­duc­tion, there was about a 4% ab­solute risk re­duc­tion,” he said, “which is the same or bet­ter than some of the re­cent tri­als that we’ve seen.”

It’s not clear when Mer­ck will file for an NDA, al­though an­a­lysts agreed a sub­mis­sion was like­ly com­ing and like­ly to suc­ceed. Still, with low pro­ject­ed sales and with gefapix­ant re­sults they Leerink viewed as dis­ap­point­ing ear­li­er this month, Scala wrote that Mer­ck might be in need of some changes.

“MRK’s cur­rent strength — thanks to Keytru­da and Vac­cines — is clear,” he wrote, “but the oxy­gen for drug man­u­fac­tur­ers are pipelines, and MRK’s ap­pears in­suf­fi­cient, rais­ing po­ten­tial for sig­nif­i­cant M&A.”

Phase III read­outs spell dis­as­ter for Genen­tech’s lead IBD drug

Roche had big plans for etrolizumab. Eyeing a hyper-competitive IBD and Crohn’s market where they have not historically been a player, the company rolled out 8 different Phase III trials, testing the antibody for two different uses across a range of different patient groups.

On Monday, Roche released results for 4 of those studies, and they mark a decided setback for both the Swiss pharma and their biotech sub Genentech, potentially spelling an end to a drug they put over half-a-decade and millions of dollars behind.

Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

Eric Shaff (Seres)

UP­DAT­ED: Af­ter a 4-year so­journ, strug­gling mi­cro­bio­me pi­o­neer Seres claims a break­out PhI­II come­back. And shares re­spond in fren­zied spike

Almost exactly 4 years ago, Seres Therapeutics $MCRB experienced one of those soul-crunching failures that can raise big questions about a biotech’s future. Out front in their pursuit of a gut punch to C. difficile infection (CDI), the Phase II test was a flat failure, and investors wiped out a billion dollars of equity value that never returned in the years that followed.

Seres, though, pressed ahead, changing out CEOs a year ago — bidding Merck vet Roger Pomerantz farewell from the C suite — and pushing through a Phase III, hoping that amping up the dosage would make the key difference. And this morning, they unveiled a claim that they had aced the Phase III and positioned themselves for a run at a landmark FDA OK.

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Warren Huff, Reata CEO

Rea­ta sug­gests Friedre­ich's atax­ia pro­gram could be de­layed, send­ing stock plung­ing

Reata Pharmaceuticals $RETA made waves last October when its drug omaveloxolone produced positive trial results in treating a rare neurological disorder, but the candidate’s path forward became much murkier Monday.

In a report of quarterly earnings, the biotech divulged that the FDA is considering delaying omaveloxolone’s NDA pending completion of a second trial. That could push back approval by at least a year given that the target population, individuals with Friedreich’s ataxia, is limited and progression of the hard-to-treat illness is notoriously slow. The Covid-19 pandemic would also hinder Reata’s ability to complete an additional trial.

Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen scores a pri­or­i­ty re­view for its Alzheimer's drug ad­u­canum­ab, mov­ing one gi­ant leap for­ward in its con­tro­ver­sial quest

Biogen scored a big win at the FDA today as regulators accepted their application for the controversial Alzheimer’s drug aducanumab and gave it a priority review.

The PDUFA date is March 7, 2021.

Significantly, Biogen says it did not use its priority review voucher to win special treatment at the FDA. The agency handed that out gratis.

That’s the ideal scenario Biogen was looking for as disappointed analysts wondered aloud about the delayed application earlier in the year.

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In­novent and Eli Lil­ly chal­lenge Mer­ck­'s mega-block­buster Keytru­da in non-small cell lung can­cer field

China-based Innovent Biologics and its multinational ally Eli Lilly shared Phase III evidence that their PD-1 inhibitor combo can delay the progression of nonsquamous non-small cell lung cancer.

But the drugmakers will face stiff competition in China from Merck’s Keytruda, the ruling PD-1 which is already approved to treat both squamous and nonsquamous NSCLC and boasts positive overall survival rates.

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Anap­tys­Bio's etokimab pro­vides more dis­ap­point­ing re­sults, rais­ing ques­tions about com­pound's fu­ture

The lead program for AnaptysBio’s in-house pipeline has hit another setback.

Etokimab, an IL-33 inhibitor, did not achieve statistically significant improvement in a Phase II trial for patients suffering from chronic rhinosinusitis with nasal polyps. Researchers measured the individuals’ bilateral nasal polyps score and sino-nasal outcome test, finding that neither improved upon a placebo after both four- and eight-week time markers, though they did demonstrate improvement over baseline levels of the examinations.

Brian Stuglik, Verastem CEO

The du­velis­ib hot pota­to is tossed to a new own­er as Ve­rastem looks to re­or­ga­nize around the pipeline

When Infinity put up duvelisib for a no-money-down instant deal, the biotech was looking for a quick exit from a clinical disaster. AbbVie had walked away from their alliance after looking at how the data stacked up in a crowded field.

And while it was approvable, it wasn’t looking pretty to anyone who thought in commercial terms.

One Big Pharma’s trash, though, was seen as a biotech treasure as a deeply troubled Verastem stepped up to grab the PI3K-delta/gamma — promising to run it across the goal lines at the FDA. And they did just that, only with little to show for it.

DFC CEO Adam Boehler and Kodak CEO Jim Continenza (Kodak)

Covid-19 roundup: Cure­Vac beefs up its uni­corn IPO dreams as bil­lion­aire own­er takes this Covid-19 mR­NA play­er on a forced march to Nas­daq; Ko­dak's $765M deal is put on hold

When CureVac initially jotted down $100 million for its IPO raise a couple of weeks ago, it seemed small. The German mRNA player, after all, had jumped into a Covid-19 race that swelled the sails of Moderna and BioNTech by tens of billions. And after raising $640 million in a slate of deals, $100 million in a hot market like this seemed like a pittance in the bigger scheme of things.

Today, we got a look at a figure that probably comes closer to the game-changing number the top execs probably have in mind. Selling 15.3 million shares at the high end of their $14 to $16 range would net a $243 million bounty. Majority owner Dietmar Hopp is putting in another €100 million, bringing the total to around $350 million. And what are the chances they want to do even better than that?

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