Kiniksa whiffs on ef­fi­ca­cy try­ing to re­pur­pose an RA pro­gram for Covid-19, but spins sur­vival 'trend­s' as a pos­i­tive

As the search for more po­ten­tial Covid-19 treat­ments con­tin­ues, Kiniksa Phar­ma­ceu­ti­cals $KN­SA has re­vealed da­ta for a re­pur­posed im­munol­o­gy can­di­date it says are pos­i­tive. But the num­bers paint a much murki­er pic­ture.

The Bermu­da-based biotech whiffed bad­ly on the pri­ma­ry end­point in the small Phase II por­tion of a Phase II/III study for its mavril­i­mum­ab pro­gram, say­ing that af­ter two weeks the pro­por­tion of pa­tients with se­vere Covid-19 who were alive and off sup­ple­men­tal oxy­gen was not sta­tis­ti­cal­ly sig­nif­i­cant com­pared to place­bo. Kiniksa al­so missed the sec­ondary end­point — pro­por­tion of pa­tients alive and with­out res­pi­ra­to­ry fail­ure af­ter four weeks — though it not­ed the da­ta moved in the right di­rec­tion over longer pe­ri­ods.

John Paoli­ni

“The da­ta showed en­cour­ag­ing trends of re­duced mor­tal­i­ty and du­ra­tion of me­chan­i­cal ven­ti­la­tion in pa­tients treat­ed with mavril­i­mum­ab, es­pe­cial­ly when con­sid­er­ing that many pa­tients in this place­bo-con­trolled study had al­ready been treat­ed with remde­sivir and/or cor­ti­cos­teroids,” Kiniksa CMO John Paoli­ni said in a state­ment.

In­vestors were most­ly mut­ed on the news, with Kiniksa shares up less than 1% in ear­ly Tues­day trad­ing.

Kiniksa had been test­ing its can­di­date in 40 pa­tients with se­vere pneu­mo­nia and hy­per­in­flam­ma­tion re­lat­ed to Covid-19 and ran­dom­ized them in an open-la­bel fash­ion in­to the drug and place­bo arms at a 1-to-1 ra­tio. All the pneu­mo­nia pa­tients need­ed sup­ple­men­tal oxy­gen, half need­ed non-in­va­sive ven­ti­la­tion, and none re­quired me­chan­i­cal ven­ti­la­tion at the base­line, Kiniksa said.

In ad­di­tion, 26 of the 40 pa­tients were on cor­ti­cos­teroids such as dex­am­etha­sone and 30 had al­so been tak­ing Gilead’s Vek­lury (remde­sivir). Kiniksa fol­lowed the pa­tients for 60 days af­ter a sin­gle in­fu­sion of mavril­i­mum­ab.

Over­all, 12 of the 21 pa­tients tak­ing mavril­i­mum­ab, or 57.1%, were alive and off oxy­gen af­ter two weeks, com­pared to 9 of 19 pa­tients (47.4%) on place­bo. That marked a rel­a­tive in­crease of 20.5%, Kiniksa said, but clocked in at a nom­i­nal p-val­ue of p=0.536 — more than a full or­der of mag­ni­tude high­er than need­ed to prove sig­nif­i­cance.

The sec­ondary al­so failed to reach the mag­ic p=0.05 num­ber, though it’s here where the biotech is point­ing to­ward the pos­i­tive trend. Af­ter four weeks, 20 of 21 pa­tients were alive and not suf­fer­ing from res­pi­ra­to­ry fail­ure, com­pared to 15 of 19 in the place­bo group. Kiniksa’s rel­a­tive in­crease in this in­stance was 20.7%, which reg­is­tered a p-val­ue of p=0.172.

Kiniksa al­so pro­vid­ed da­ta re­gard­ing the deaths of pa­tients in both arms. Fol­low­ing the four-week sec­ondary end­point pe­ri­od, there was one death in the mavril­i­mum­ab arm and three on place­bo, good for a nom­i­nal p=0.222. Af­ter the full 60-day ob­ser­va­tion pe­ri­od, there was one ad­di­tion­al death in the place­bo group, which low­ered the nom­i­nal p-val­ue to 0.108.

Tues­day’s da­ta mark the lat­est in a string of ex­per­i­men­tal drugs re­pur­posed to fight Covid-19 that show ini­tial pos­i­tive signs of ef­fi­ca­cy but al­so pose as many ques­tion as they an­swer. Vek­lury has been the most promi­nent of the bunch, hav­ing demon­strat­ed a re­duc­tion in re­cov­ery time by five days in hos­pi­tal­ized Covid-19 pa­tients and by sev­en days in pa­tients re­quir­ing oxy­gen, in a NI­AID-spon­sored tri­al.

But the WHO has come out against Gilead’s drug, find­ing Vek­lury did not have any sub­stan­tial ef­fect on im­prov­ing mor­tal­i­ty rates, re­duc­ing the amount of pa­tients need­ing ven­ti­la­tors or short­en­ing hos­pi­tal stays. De­spite this, the FDA hand­ed down a full ap­proval for Vek­lury in Oc­to­ber and said it found the for­mer tri­al “bet­ter suit­ed” for a time-to-re­cov­ery end­point since the WHO study was open la­bel.

It re­mains to be seen whether Tues­day’s mavril­i­mum­ab da­ta will help or hurt its chances as a Covid-19 drug giv­en the ever-shift­ing land­scape of tack­ling the dis­ease. Mavril­i­mum­ab is a mon­o­clon­al an­ti­body that tar­gets GM-CS­FRα, hav­ing made it through a Phase IIb study for rheuma­toid arthri­tis. Kiniksa’s lead in­di­ca­tion for mavril­i­mum­ab is gi­ant cell ar­teri­tis, a rare in­flam­ma­to­ry dis­ease of medi­um-to-large ar­ter­ies.

The com­pa­ny is fur­ther eval­u­at­ing the pro­gram in Covid-19 in a glob­al, adap­tive de­sign Phase II/III tri­al, and is ex­pect­ing Phase II da­ta in the first half of next year.

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

So­cial: Kiniksa web­site

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George Yancopoulos (L) and Len Schleifer (Regeneron)

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Anthony Fauci, NIAID director (AP Images)

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Pascal Soriot, AP

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