J&J re­leas­es PhI­II safe­ty blue­print for Covid-19 vac­cine tri­al. How does it stack up to Mod­er­na, Pfiz­er and As­traZeneca?

Along with the ini­ti­a­tion of its Phase III Covid-19 vac­cine study an­nounced Wednes­day morn­ing, John­son & John­son al­so re­leased its tri­al pro­to­col, giv­ing an in­side look at how the com­pa­ny is con­duct­ing its late-stage re­search.

The move comes af­ter the oth­er three com­pa­nies con­duct­ing Phase III’s in the US — Mod­er­na, Pfiz­er and As­traZeneca — each dis­closed their own tri­al blue­prints with­in the last week. Though the re­lease of such pro­to­cols is typ­i­cal­ly done af­ter tri­als have been com­plet­ed, drug de­vel­op­ers had come un­der in­tense pres­sure af­ter a brief safe­ty scare in an As­traZeneca tri­al and amid grow­ing con­cern of a po­lit­i­cal­ly mo­ti­vat­ed vac­cine au­tho­riza­tion.

J&J’s ef­fi­ca­cy and Covid-19 event tar­gets are rough­ly on par with its com­peti­tors. The com­pa­ny is tar­get­ing 60% ef­fi­ca­cy for its one-shot mod­i­fied ade­n­ovirus can­di­date, the same lev­el sought by Mod­er­na and Pfiz­er (As­traZeneca is tar­get­ing 50% ef­fi­ca­cy). At com­ple­tion, the 60,000-pa­tient J&J tri­al would need 154 cas­es of Covid-19 to prove ef­fi­ca­cy, sim­i­lar to the oth­er num­bers. In their own blue­prints, Pfiz­er said they need 164 events, Mod­er­na 151 and As­traZeneca 150.

There are, how­ev­er, two no­table dif­fer­ences be­tween J&J’s tri­al and the pre­vi­ous three that jump out right off the bat. First­ly, J&J’s pri­ma­ry end­point is fo­cus­ing more on mod­er­ate and se­vere coro­n­avirus in­fec­tions than mild cas­es. Ac­cord­ing to Scripps pro­fes­sor Er­ic Topol, there is some over­lap be­tween the cas­es in­clud­ed in the pri­ma­ry end­point with Mod­er­na and As­traZeneca, but the cri­te­ria are “clear­ly more strin­gent” than Pfiz­er’s.

And sec­ond, J&J is not plan­ning on con­duct­ing any in­ter­im analy­ses un­less four spe­cif­ic con­di­tions are met. Those con­di­tions are as fol­lows:

1. The first 50% of planned par­tic­i­pants had at least 2 months of fol­low-up af­ter vac­ci­na­tion.

2. A min­i­mum of 6 Covid-19 cas­es for the ≥60 years age group.

3. At least 20 cas­es meet­ing the pri­ma­ry end­point de­f­i­n­i­tion of mod­er­ate to se­vere/crit­i­cal Covid-19.

4. A sub­set of at least 5 cas­es meet­ing the pri­ma­ry end­point de­f­i­n­i­tion of se­vere/crit­i­cal Covid-19.

Once these oc­cur, the pro­to­cols say that mon­i­tor­ing for ef­fi­ca­cy will take place once a week by the DSMB un­til J&J reach­es the mag­ic 154 num­ber.

That first con­di­tion falls in line with a new set of FDA guide­lines that the agency is re­port­ed­ly ex­pect­ed to re­lease soon for vac­cine EUAs, per the Wash­ing­ton Post. The new rules in­clude re­quire­ments to fol­low sub­jects for a me­di­an of at least 60 days fol­low­ing the sec­ond dose of the vac­cine and ask drug­mak­ers to ac­crue at least 5 cas­es of se­vere Covid-19 in the place­bo group.

J&J al­so ap­pears to have struc­tured their tri­al to in­clude that sec­ond new guide­line, re­quir­ing the fol­low­ing for a suc­cess­ful pri­ma­ry end­point con­clu­sion:

1. Es­tab­lish­ing the hy­poth­e­sis H1: VE>30% for the pri­ma­ry end­point AND

2. A fa­vor­able split vac­cine: place­bo for the sub­set of pri­ma­ry end­points meet­ing the se­vere/crit­i­cal COVID-19 case de­f­i­n­i­tion (ex­pressed as a VE point es­ti­mate against se­vere/crit­i­cal Covid-19 mol­e­c­u­lar­ly con­firmed end­points ≥50%) and a min­i­mum of 5 events in the place­bo group.

The po­lit­i­cal pres­sure placed on vac­cine mak­ers has been pro­found through­out the Covid-19 pan­dem­ic, but scruti­ny has on­ly es­ca­lat­ed with Pres­i­dent Don­ald Trump’s re­peat­ed promis­es of a vac­cine be­fore No­vem­ber 3rd. Al­so last week, HHS sec­re­tary Alex Azar ef­fec­tive­ly set the FDA staff on no­tice say­ing that his sig­na­ture is re­quired on all rule­mak­ing.

On­ly Pfiz­er CEO Al­bert Bourla has of­fered a time­line close to that promise, say­ing pub­licly that his com­pa­ny will know whether or not its can­di­date works in Oc­to­ber. Mod­er­na’s pres­i­dent, Stephen Hoge, said in an in­ter­view with CBS Evening News last week the biotech will know by No­vem­ber if its own vac­cine is safe and ef­fec­tive.

As­traZeneca’s Phase III tri­al re­mains on hold in the US af­ter a sus­pect­ed case of trans­verse myelitis popped up af­ter a vol­un­teer took their sec­ond dose of the vac­cine. The com­pa­ny has not con­firmed the di­ag­no­sis, and a doc­u­ment post­ed by Ox­ford Uni­ver­si­ty with­in the last two weeks sug­gest­ed that the vac­cine was not linked to the con­di­tion.

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

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Michel Vounatsos, Biogen CEO (via YouTube)

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HHS secretary Alex Azar (at the podium) and FDA commissioner Stephen Hahn (Pete Marovich/Getty Images)

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Jean-Pierre Sommadossi, Atea president and CEO (file photo)

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John Maraganore, Alnylam CEO (Scott Eisen/Bloomberg via Getty Images)

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