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.

Michel Vounatsos, Biogen CEO (via YouTube)

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Pfizer CEO Albert Bourla (Drew Angerer/Getty Images)

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