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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Steve Harr (L) and Hans Bishop

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Early Wednesday, an EU Commission spokeswoman said that “the representative of AstraZeneca had announced this morning, had informed us this morning that their participation is not confirmed, is not happening.” But an AstraZeneca spokesperson later called the reports “not accurate.”

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The company is partnering with Japan’s Asahi Kasei Pharma on an experimental drug for chronic pain, acquiring the rights for the P2X7 receptor antagonist program dubbed AK1780. Lilly will shell out a pretty penny for the program, promising up to $410 million total should each milestone payment come to pass.

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Bob Nelsen (Michael Kovac/Getty Images)

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