Af­ter two rounds of mixed da­ta, Eli Lil­ly im­press­es an­a­lysts with new Covid-19 an­ti­body re­sults. And ex­ecs want an EUA now

Eli Lil­ly has more da­ta from their Covid-19 neu­tral­iz­ing an­ti­bod­ies — da­ta, they say, should war­rant an FDA OK.

The Big Phar­ma said Wednes­day that a cock­tail of two mon­o­clon­al an­ti­bod­ies looked safe and re­duced vi­ral load in Covid-19 pa­tients. It al­so al­le­vi­at­ed symp­toms and re­duced ER vis­its and hos­pi­tal­iza­tion rate com­pared to place­bo, ap­pear­ing over­all to pro­vide bet­ter re­sults than a sin­gle Lil­ly an­ti­body showed in Sep­tem­ber and to com­pare fa­vor­ably with the Re­gen­eron an­ti­body cock­tail that Pres­i­dent Trump re­ceived last week.

“To date we have been large­ly dis­ap­point­ed in the clin­i­cal re­sults for COVID-19 mAbs,” Baird’s Mad­hu Ku­mar said in a note, sin­gling out the first Lil­ly and Re­gen­eron da­ta. “In con­trast, to­day’s … cock­tail re­sults look pret­ty en­cour­ag­ing.”

Eli Lil­ly al­so dis­closed that, de­spite mixed sig­nals in a Phase II, they had ap­plied for an EUA for the sin­gle an­ti­body. With some an­a­lysts ex­pect­ing an im­mi­nent EUA for Re­gen­eron, that could quick­ly dou­ble the num­ber of FDA-au­tho­rized Covid-19 ther­a­pies from two to four.

These new da­ta mark the third batch of re­sults from neu­tral­iz­ing mon­o­clon­al an­ti­bod­ies, a close­ly-watched method to treat or pre­vent Covid-19 that re­searchers and a hand­ful of ma­jor com­pa­nies have been rac­ing to de­vel­op for near­ly a year.

Al­though tri­als are un­der­way across a range of pa­tient types, re­searchers ex­pect­ed the an­ti­bod­ies to be more ef­fec­tive in ear­li­er-stage pa­tients than lat­er ones. But the re­sults Eli Lil­ly re­leased on a sin­gle an­ti­body last month left as many as ques­tions as an­swers. A medi­um dose of the drug sig­nif­i­cant­ly re­duced vi­ral loads in ear­ly-stage pa­tients but nei­ther the high dose nor the low dose did.

The re­sults for the an­ti­body cock­tail, how­ev­er, paint a clear­er pic­ture. At 2,800 mg, the drug sig­nif­i­cant­ly re­duced vi­ral lev­els com­pared to place­bo by day 11 in symp­to­matic but not hos­pi­tal­ized pa­tients, meet­ing the pri­ma­ry end­point. The re­sults were al­so sig­nif­i­cant for day 3 and day 7.

Con­sis­tent with the de­cline in vi­ral load, pa­tients who re­ceived the an­ti­body al­so saw a greater de­cline in symp­toms over 11 days. And, al­though the re­sults were on­ly nar­row­ly sig­nif­i­cant (P=0.049), pa­tients in the drug arm saw few­er hos­pi­tal­iza­tions and ER vis­its, with 0.9% of an­ti­body pa­tients and 5.8% of place­bo pa­tients wind­ing up in med­ical cen­ters.

Al­though more Lil­ly da­ta would be need­ed for a full com­par­i­son, these num­bers com­pare fa­vor­ably with the da­ta Re­gen­eron un­veiled last week.

The New York-based biotech, which had been the fron­trun­ner in the an­ti­body race af­ter show­ing ground­break­ing da­ta from an Ebo­la an­ti­body last year, re­vealed sta­tis­ti­cal­ly sig­nif­i­cant re­sults re­duc­tions in vi­ral load from their first 275 pa­tients. There were al­so nu­mer­i­cal im­prove­ments in symp­tom al­le­vi­a­tion and hos­pi­tal­iza­tion rates but the re­sults weren’t sig­nif­i­cant.

Still, the big biotech cau­tioned that far more pa­tients and more da­ta were com­ing, and Baird’s Bri­an Sko­r­ney saw to­day’s Eli Lil­ly da­ta as po­ten­tial ev­i­dence that the re­duc­tions in vi­ral load Re­gen­eron saw would ul­ti­mate­ly trans­late in­to im­por­tant re­duc­tions in symp­toms and hos­pi­tal­iza­tions.

“All told, while ear­ly clin­i­cal da­ta from Re­gen­eron’s REGN-COV2 cock­tail are lim­it­ed to date,” he said in a note to in­vestors, “we do find the clin­i­cal da­ta from Eli Lil­ly’s two drug com­bi­na­tion quite en­cour­ag­ing and be­lieve that this da­ta may pro­vide proof-of-con­cept that re­duc­ing vi­ral load with an an­ti­body cock­tail could lead to a clin­i­cal ben­e­fit.”

Eli Lil­ly said they will file for an EUA for the cock­tail. They’ve al­ready re­quest­ed au­tho­riza­tion for the sin­gle an­ti­body at the low dose of 700 mg, say­ing they saw “sim­i­lar clin­i­cal ef­fects” across dos­es in their Phase II study. Re­gen­eron has ar­gued sim­i­lar­ly, say­ing they would dis­cuss a low-dose EUA from the agency de­spite on­ly the high dose reach­ing sta­tis­ti­cal sig­nif­i­cance. Lil­ly, un­like Re­gen­eron, has not re­leased any da­ta for the 700 mg dose.

Giv­en the stronger da­ta from the com­bi­na­tion, Baird’s Ku­mar said they did “not ex­pect re­al up­take” for the sin­gle an­ti­body, re­gard­less of whether it was au­tho­rized. Lil­ly, though, has made clear that far more of the monother­a­py will be avail­able soon­er than the com­bi­na­tion ther­a­py.

The com­pa­ny said to­day that up to 1 mil­lion dos­es could be avail­able in the fourth quar­ter of 2020, com­pared to 50,000 dos­es of the com­bo. Man­u­fac­tur­ing of the cock­tail would pick up in Q1 2021, fu­eled by a new agree­ment with Am­gen. Re­gen­eron is aim­ing for 300,000 dos­es of its cock­tail this year and 250,000 dos­es per month next year.

There will like­ly be far more de­mand than ei­ther com­pa­ny can meet, Cred­it Su­isse’s Evan Seiger­man not­ed.

Lil­ly’s sin­gle an­ti­body, LY­CoV55, came from Cana­di­an start­up Ab­Cellera. The cock­tail com­bined LY­CoV555 with an an­ti­body de­vel­oped by the Shang­hai-based biotech Jun­shi Bio­sciences. Lil­ly has now named them bam­lanivimab and ete­se­vimab.

Ku­mar added that the stronger re­sults now seen in the two cock­tail tri­als and the mixed re­sults from the sin­gle Lil­ly an­ti­body might not bode well for the third con­tender in the race, Vir. The Glax­o­SmithK­line-part­nered com­pa­ny re­cent­ly put a sin­gle an­ti­body in­to Phase III they hope can be as or more pow­er­ful than Re­gen­eron’s cock­tail. Ku­mar, though, ar­gued pre­clin­i­cal al­ready points to a less po­tent mol­e­cule and the re­cent cock­tail da­ta leave lit­tle wig­gle room.

“Over­all, giv­en VIR-7831’s in­fe­ri­or bio­chem­i­cal and dos­ing pro­file,” he said, “to­day’s bam­lanivimab/ete­se­vimab da­ta leave no room to hide for a bio­chem­i­cal­ly in­fe­ri­or and un­der-dosed COVID-19 mAb in the Phase 2/3 COMET-ICE tri­al.”

For a look at all End­points News coro­n­avirus sto­ries, check out our spe­cial news chan­nel.

UP­DAT­ED: Mer­ck pulls Keytru­da in SCLC af­ter ac­cel­er­at­ed nod. Is the FDA get­ting tough on drug­mak­ers that don't hit their marks?

In what could be an early shot in the battle against drugmakers that whiff on confirmatory studies to support accelerated approvals, the FDA ordered Bristol Myers Squibb late last year to give up Opdivo’s approval in SCLC. Now, Merck is next on the firing line — are we seeing the FDA buckling down on post-marketing offenders?

Merck has withdrawn its marketing approval for PD-(L)1 inhibitor Keytruda in metastatic small cell lung cancer as part of what it describes as an “industry-wide evaluation” by the FDA of drugs that do not meet the post-marketing checkpoints on which their accelerated nods were based, the company said Monday.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,400+ biopharma pros reading Endpoints daily — and it's free.

Michael Shpigelmacher

Khosla joins bet on un­con­ven­tion­al start­up look­ing to send drug de­liv­er­ing ro­bots in­to the brain

When Michael Shpigelmacher started the project, he knew he’d have to fund it himself. Every other effort of its kind was academic, rejected as too risky by investors.

Shpigelmacher, a robotics geek and entrepeneur who had drifted into consulting for pharma, wanted to build the real-life equivalent of technology from the 1960s film Fantastic Voyage, the one where a submarine crew is shrunk to “about the size of a microbe” and sent on a mission to repair a scientist’s brain. He scanned the literature, found the lab that was working on the most advanced project — at the Max Planck Institute in Germany, it turned out — and started funding them with money from his own account, along with some seed cash from friends and family.

Af­ter bail­ing on Covid-19 vac­cines, Mer­ck will team up with J&J to pro­duce its shot as part of un­usu­al Big Phar­ma pact

Merck took a big gamble when it opted to jump into the Covid-19 vaccine race late, and made an equally momentous decision to back out in late January. Now, looking to chip in on the effort, Merck reportedly agreed to team up with one of the companies that has already crossed the finish line.

President Joe Biden on Tuesday is expected to announce a partnership between drugmakers Merck and Johnson & Johnson to jointly produce J&J’s recombinant protein Covid-19 vaccine that received the FDA’s emergency use authorization Saturday, the Washington Post reported.

Paul Sekhri

The next big biotech su­per­star? Paul Sekhri has some thoughts on that

It occasionally occurs to Paul Sekhri that if they pull this off, his company will be on the front page of the New York Times and a lead story in just about every major news outlet on the planet. He tries not to dwell on it, though.

“I just want to be laser-focused on getting to that point,” Sekhri says, before acknowledging, “Yes, it absolutely crossed my mind.”

Sekhri, a longtime biopharma executive with tenures at Sanofi and Novartis, is now entering year three as CEO of eGenesis, the biotech that George Church protégé Luhan Yang founded to genetically alter pigs so that they can be used for organ transplants. He led them through one megaround and has just closed another, raising $125 million from 17 different investors to push the first-ever (humanized) pig to human transplants into the clinic.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,400+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: Feds clear the road for J&J to start de­liv­er­ing mil­lions of dos­es of their Covid-19 vac­cine — but frets linger about run­ner-up sta­tus

All the pieces needed to trigger a third wave of Covid-19 vaccine supply to start washing over the US fell neatly into place over the weekend.

After providing for a brief mime of regulatory judiciousness, the FDA stamped their emergency approval on J&J’s Covid-19 vaccine Saturday, adding to the Biden administration’s plan aimed at ending the pandemic in the near term — at least in the US. The CDC came through on Sunday with its stamp of approval and J&J is reportedly expected to start delivering vaccine sometime in the next few days.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,400+ biopharma pros reading Endpoints daily — and it's free.

Amit Munshi, Arena

One of Are­na's top drugs flops in a PhI­Ib study for IBS pain. But re­searchers tease out a pos­si­ble path for­ward as CEO ex­plores 's­trate­gic op­tion­s'

Four years ago, when Arena CEO Amit Munshi cut its ties to a troubled weight drug and doubled down on the pipeline, a cannabinoid receptor 2 agonist figured prominently in the biotech’s future. On Tuesday evening, however, Munshi’s high hopes for the drug took a nasty hit after it failed a Phase IIb study for patients with irritable bowel syndrome pain.

Put through a randomized pace with 273 patients, researchers said it flat failed the primary endpoint among the large group with abdominal pain. But they quickly went on to highlight subgroup data, always a tricky and controversial ploy, where they spotlighted a positive p value for patients with moderate to severe pain who received the high dose of the drug — one of 3 provided in the study.

Bob Nelsen (Photo by Michael Kovac/Getty Images)

With stars aligned and cash in re­serve, Bob Nelsen's Re­silience plans a makeover at 2 new fa­cil­i­ty ad­di­tions to its drug man­u­fac­tur­ing up­start

Bob Nelsen’s new, state-of-the-art drug manufacturing initiative is taking shape.

Just 3 months after gathering $800 million of launch money, a dream team board and a plan to shake up a field where he found too many bottlenecks and inefficiencies for the era of Covid-19, Resilience has snapped up a pair of facilities now in line for a retooling.

The company has acquired a 310,000-square-foot plant in Boston from Sanofi along with a 136,000-square-foot plant in Ontario to add to a network which CEO Rahul Singhvi says is just getting started on building his company’s operations up. The Sanofi deal comes with a contract to continue manufacturing one of its drugs.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,400+ biopharma pros reading Endpoints daily — and it's free.

CEO Marco Taglietti (Scynexis)

'N­ev­er been more ur­gent:' Scynex­is looks to tack­le su­per­bug cri­sis with late-stage read­out for an­ti­fun­gal hope­ful

As the superbug crisis heats up around the world, Scynexis says it has new data from two interim analyses that prove its antifungal has the potential to treat a broad range of infections.

“The need for new anti-infectives capable of fighting the most resistant pathogens has never been more urgent as we confront the ongoing COVID-19 global pandemic,” CEO Marco Taglietti said in a statement.

A spot­light schiz­o­phre­nia drug in Neu­ro­crine's $2B Take­da deal flunks its first ma­jor test. But it's not giv­ing up yet

When Takeda spun out a pipeline of experimental psychiatry drugs to Neurocrine in a $2 billion deal amid a post-merger shakeout, R&D chief Andy Plump described the therapies as “very interesting but still difficult.”

On Tuesday, we got some idea of how difficult.

San Diego-based Neurocrine revealed that one of the three spotlight clinical programs they’d acquired failed the primary endpoint in a Phase II trial for schizophrenia, registering a negative outcome on the change from baseline in the positive and negative syndrome scale/negative symptom factor score (PANSS NSFS).