WHO says remde­sivir has lit­tle ef­fect in hos­pi­tal­ized Covid-19 — but Gilead calls new da­ta 'in­con­sis­ten­t' with pre­vi­ous find­ings

A new WHO study is throw­ing cold wa­ter on the ef­fec­tive­ness on remde­sivir in Covid-19 pa­tients.

Af­ter con­duct­ing a large clin­i­cal tri­al look­ing in­to remde­sivir and three oth­er treat­ments, the WHO has found that none had any sub­stan­tial ef­fect on im­prov­ing mor­tal­i­ty rates, re­duc­ing the amount of pa­tients need­ing ven­ti­la­tors or short­en­ing hos­pi­tal stays. The oth­er ther­a­pies in the study were hy­drox­y­chloro­quine, lopinavir and in­ter­fer­on.

The study first came to light fol­low­ing a Fi­nan­cial Times re­port Thurs­day af­ter­noon. With­in the preprint, WHO re­searchers said the tri­al was de­signed to see how the drugs af­fect­ed in-hos­pi­tal mor­tal­i­ty.

With remde­sivir, their find­ings didn’t con­firm what the NIH had re­port­ed from ACTT-1: that the drug had “mod­er­ate­ly re­duced time to re­cov­ery.” In SOL­I­DAR­I­TY, it had no ma­te­r­i­al ef­fects on ven­ti­la­tion ini­ti­a­tion or time to dis­charge.

Per­haps more im­por­tant­ly, the new re­sults shat­tered any hopes of mor­tal­i­ty ben­e­fits — where the pre­vi­ous study saw a slight nu­mer­i­cal im­prove­ment that’s not sta­tisi­cal­ly sig­nif­i­cant — any­one may have held:

This ab­solute­ly ex­cludes the sug­ges­tion that Remde­sivir can pre­vent a sub­stan­tial frac­tion of all deaths. The con­fi­dence in­ter­val is com­fort­ably com­pat­i­ble with pre­ven­tion of a small frac­tion of all deaths, but is al­so com­fort­ably com­pat­i­ble with pre­ven­tion of no deaths (which would be con­sis­tent with the ap­par­ent lack of any re­duc­tion by Remde­sivir in the ini­ti­a­tion of ven­ti­la­tion or the du­ra­tionof hos­pi­tal­iza­tion in Sol­i­dar­i­ty).

In a state­ment emailed to End­points News, Gilead said it is aware of the re­port and “con­cerned” that the study hasn’t un­der­gone peer re­view.

“The emerg­ing da­ta ap­pear in­con­sis­tent with more ro­bust ev­i­dence from mul­ti­ple ran­dom­ized, con­trolled stud­ies pub­lished in peer-re­viewed jour­nals val­i­dat­ing the clin­i­cal ben­e­fit of Vek­lury,” the state­ment read, re­fer­ring to the com­mer­cial name of remde­sivir. “The tri­al de­sign pri­or­i­tized broad ac­cess, re­sult­ing in sig­nif­i­cant het­ero­gene­ity in tri­al adop­tion, im­ple­men­ta­tion, con­trols and pa­tient pop­u­la­tions and con­se­quent­ly, it is un­clear if any con­clu­sive find­ings can be drawn from the study re­sults.”

The WHO’s tri­al is one of the biggest on­go­ing stud­ies in­to Covid-19 treat­ments, and drugs can be added or re­moved at any time. The remde­sivir arm en­rolled 2,750 pa­tients who were treat­ed for 10 days, with a 200 mg dose ad­min­is­tered on the first day and 100 mg dos­es giv­en each of the fol­low­ing days. The pa­per on­ly showed re­sults cov­er­ing the pe­ri­od from March to Oc­to­ber.

Baird’s Bri­an Sko­r­ney took a grim view of Thurs­day’s news, all but de­clar­ing an end to the po­ten­tial full FDA ap­proval that’s cur­rent­ly un­der re­view. Sko­r­ney stopped short of say­ing the FDA would pull its emer­gency use au­tho­riza­tion, but said Gilead will like­ly see much more lim­it­ed use of remde­sivir out­side the US.

“Giv­en the sub­stan­tial size of this study and ab­sence of even a hint of an ef­fect, it’s hard to see these re­sults as any­thing but ex­tra­or­di­nar­i­ly neg­a­tive for the out­look that remde­sivir could have any re­al im­pact on the pan­dem­ic,” Sko­r­ney wrote to in­vestors.

Remde­sivir has had a long and bumpy road through­out the pan­dem­ic, and it’s cur­rent­ly not ap­proved in any in­di­ca­tion. Orig­i­nal­ly de­vel­oped as a treat­ment for Ebo­la, remde­sivir won or­phan drug sta­tus in late March on­ly for Gilead to give it up two days lat­er fol­low­ing crit­i­cism that the com­pa­ny had rushed to ob­tain the des­ig­na­tion, which comes with 7 years of mar­ket ex­clu­siv­i­ty among oth­er reg­u­la­to­ry ben­e­fits.

Then in May, the agency grant­ed it a par­tial EUA to treat se­vere Covid-19 cas­es af­ter the tri­al con­duct­ed by the NI­AID sug­gest­ed that the drug cut the av­er­age time to re­cov­ery to 11 days in the drug arm of a tri­al, com­pared to 15 in the con­trol group. Remde­sivir’s EUA was ex­pand­ed in Au­gust to in­clude the treat­ment of all hos­pi­tal­ized adults and chil­dren, thanks to an­oth­er Gilead-led tri­al that showed mod­est ef­fi­ca­cy.

That study gar­nered mixed re­ac­tions, how­ev­er, as a 10-day dos­ing arm of remde­sivir didn’t lead to a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment over stan­dard of care. That re­sult came in spite of the ther­a­py meet­ing its pri­ma­ry end­point, as pa­tients giv­en a 5-day dose of remde­sivir were 65% more like­ly to show “clin­i­cal im­prove­ment.”

Gilead has al­so drawn scruti­ny over its pric­ing of the treat­ment, charg­ing gov­ern­ments out­side the US $2,340 for a 5-day course and $3,120 for Amer­i­can in­sur­ers.

When Pres­i­dent Don­ald Trump was di­ag­nosed with Covid-19 a few weeks ago, remde­sivir was one of three treat­ments he re­ceived along­side Re­gen­eron’s ex­per­i­men­tal an­ti­body cock­tail and dex­am­etha­sone, a cheap steroid that’s re­duced mor­tal­i­ty in the UK RE­COV­ERY tri­al.

Remde­sivir is one of on­ly three treat­ments to have re­ceived an EUA from the FDA, along­side hy­drox­y­chloro­quine and con­va­les­cent plas­ma, which were au­tho­rized in March and Au­gust, re­spec­tive­ly. The for­mer, an an­ti-malar­i­al, had its EUA re­voked in June.

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