Eli Lil­ly launch­es PhI­II JAK study, aim­ing for the first drug to low­er mor­tal­i­ty in Covid-19

Soon af­ter the NIH an­nounced in late April that Eli Lil­ly’s JAK in­hibitor baric­i­tinib would be the sec­ond drug test­ed in the tri­al that had proven remde­sivir ef­fec­tive, doc­tors around the world be­gan telling Lil­ly that that wouldn’t be enough.

Since the ear­ly days of the pan­dem­ic, the In­di­anapo­lis phar­ma had heard from doc­tors in Italy, Spain and else­where who, fac­ing hos­pi­tals full of pa­tients with a dis­ease with no known treat­ment, used the JAK in­hibitor — known com­mer­cial­ly as the rheuma­toid arthri­tis drug  Olu­mi­ant — off-la­bel. The doc­tors want­ed to know con­clu­sive­ly if it worked. But the NIH tri­al could on­ly tell them if, when com­bined with remde­sivir, it worked bet­ter than remde­sivir alone. And then on­ly in the more se­vere pa­tients.

Pa­trik Jon­s­son

“We de­cid­ed it’s our oblig­a­tion,” Eli Lil­ly Bio-Med­i­cines Pres­i­dent Pa­trik Jon­s­son told End­points News. “For sci­en­tif­ic rea­sons but most im­por­tant­ly for health­care providers and for pa­tients, we need­ed to un­der­stand the over­all ef­fects of Olu­mi­ant/baric­i­tinib alone in treat­ing Covid-19.”

Lil­ly is now launch­ing their own Phase III, 400-per­son study to test whether baric­i­tinib alone can beat place­bo in treat­ing Covid-19. Spread across 15 sites in 4 coun­tries, the tri­al will test the idea that the drug not on­ly has po­ten­tial to man­age the cy­tokine storms that af­flict late-stage pa­tients, but al­so treat the dis­ease in its mild to mod­er­ate man­i­fes­ta­tions.

Un­like some oth­er ma­jor Covid-19 tri­als, in­clud­ing most no­tably the first part of the NIH study and sev­er­al Gilead ran on remde­sivir, the tri­al’s pri­ma­ry end­point won’t be about time to re­cov­ery or how symp­toms im­prove on an 8-point scale. In­stead, the ques­tion will be sim­ple: At day 28, is there a sig­nif­i­cant­ly few­er num­ber of pa­tients on the drug arm who have died or gone to ven­ti­la­tion than in the place­bo arm?

“Since the com­mu­ni­ty got the da­ta on remde­sivir in the be­gin­ning of May, we are set­ting the bar high­er,” Jonn­son said. “We need to add in­cre­men­tal val­ue.”

The new Lil­ly tri­al joins a throw-any­thing-against-the-wall now cov­ered in tra­di­tion­al Chi­nese and In­di­an med­i­cines, im­mune block­ers and im­mune boost­ers, an­ti-co­ag­u­lants, and an­tivi­rals of myr­i­ad ori­gins. Clin­i­cal­tri­als.gov now lists 1,211 dif­fer­ent in­ter­ven­tion­al Covid-19 tri­als.

Still, re­searchers say there’s rea­son to be­lieve that baric­i­tinib has bet­ter odds than oth­ers. It was first iden­ti­fied as a po­ten­tial treat­ment in Feb­ru­ary by the British biotech Benev­o­lent AI as part of a ma­chine learn­ing-based drug screen.

Vin­cent Mar­coni

“Baric­i­tinib, be­ing a JAK in­hibitor, has some ad­van­tages on some of the oth­er cy­tokine agents,” Vin­cent Mar­coni, an in­fec­tious dis­ease spe­cial­ist at Emory Uni­ver­si­ty, told End­points.

Like the Roche drug IL-6 block­ing drug Actem­ra — which has shown po­ten­tial in ear­ly stud­ies — baric­i­tinib blocks some of the cy­tokines, or im­mune sig­nals, that can lead to an over­ac­tive in­flam­ma­to­ry re­sponse in some pa­tients. But un­like IL-6 block­ers, Mar­coni said, baric­i­tinib blocks sev­er­al im­mune path­ways as op­posed to just one.

“The hope with a sin­gle cy­tokine ther­a­py is that maybe you can get the crit­i­cal one and that’s all that’s need­ed, and the oth­er ones don’t play much of a role. We don’t know the an­swer to the yet,” Mar­coni said. “But with JAK-STAT in­hibitors like baric­i­tinib, we’re re­al­ly tar­get­ing mul­ti­ple of these cy­tokine path­ways. I think that’s one of the main at­trac­tive ra­tio­nales.”

With virus-neu­tral­iz­ing an­ti­bod­ies now en­ter­ing hu­man test­ing — in­clud­ing two from Eli Lil­ly — to great med­ical at­ten­tion, Mar­coni said he could imag­ine a fu­ture where sev­er­al of the most ef­fec­tive ther­a­pies were used in com­bi­na­tion, as in HIV treat­ments.

Any coro­n­avirus study will fluc­tu­ate with the case counts in tri­al site cities, but Lil­ly is hop­ing to have re­sults by Sep­tem­ber. The NIH hasn’t an­nounced a time­line, but the com­pa­ny said it is al­ready more than half-en­rolled.

Pa­tients in the tri­al will still be able to take remde­sivir if their doc­tors pre­scribe it, al­though pa­tients would not nec­es­sar­i­ly fit cri­te­ria for both, said Patrick Mil­li­gan, an in­fec­tious dis­ease spe­cial­ist at the Com­mu­ni­ty Health Net­work in In­di­anapo­lis, one of the study sites. Al­though guid­ance for remde­sivir can vary state to state and even hos­pi­tal to hos­pi­tal, it is gen­er­al­ly giv­en to lat­er-stage pa­tients.

Mil­li­gan said his hos­pi­tal has giv­en baric­i­tinib to Covid-19 pa­tients since the ear­ly days of the pan­dem­ic and the pa­tients who re­ceived it seemed to do bet­ter than those that got Actem­ra. But the re­sults were hard to parse; the pa­tients who got Actem­ra were gen­er­al­ly al­ready in worse con­di­tion.

”This is all anec­do­tal. It’s use­ful. If that’s the da­ta you have, that’s fine,” he told End­points. But now they were join­ing the study “to hope­ful­ly help get some de­fin­i­tive an­swers.”

So­cial: Dar­ron Cum­mings, AP Im­ages

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