J&J ad­comm live blog: Com­mit­tee votes 22-0 to rec­om­mend an FDA OK for the J&J vac­cine, set­ting up 3rd US Covid-19 jab

The US could have a third au­tho­rized Covid-19 vac­cine with­in hours.

The FDA’s ad­vi­so­ry com­mit­tee vot­ed unan­i­mous­ly — 22-0 — to rec­om­mend the agency is­sue an emer­gency use au­tho­riza­tion for J&J’s vac­cine. If they fol­low the prece­dent of the Pfiz­er and Mod­er­na vac­cine, the FDA will like­ly au­tho­rize the vac­cine by Sat­ur­day, im­me­di­ate­ly adding a few mil­lion dos­es to the US sup­ply and adding a 100 mil­lion by June. An au­tho­riza­tion would give the world its first sin­gle-dose vac­cine, a ma­jor weapon in the ef­fort to vac­ci­nate the world and bring the virus to heel, par­tic­u­lar­ly in rur­al and de­vel­op­ing ar­eas.

“I think it was a rel­a­tive­ly easy call,” ob­served Er­ic Ru­bin, New Eng­land Jour­nal of Med­i­cine ed­i­tor-in-chief and com­mit­tee mem­ber.

One key con­cern through­out the day’s dis­cus­sions cen­tered around one sub­group in J&J’s tri­al: The shot ap­peared on­ly 42% ef­fec­tive in adults over the age of 60 with co­mor­bidi­ties 28 days af­ter vac­ci­na­tion. But com­mit­tee mem­bers agreed that it was too small a pop­u­la­tion to draw sweep­ing con­clu­sions from. Oth­er ev­i­dence point­ed to high­er ef­fi­ca­cy and the pub­lic health con­cern was too great.

“De­spite the con­cerns that were raised in the dis­cus­sion, we are still in the midst of this dead­ly pan­dem­ic,” Archana Chat­ter­jee, dean of Chica­go Med­ical School and a com­mit­tee mem­ber said. “There is a short­age of vac­cines that were au­tho­rized and I think this vac­cine will help meet the need at the mo­ment.”

Mul­ti­ple ad­vi­sors em­pha­sized that peo­ple should get what­ev­er vac­cine be­comes avail­able to them when it be­comes avail­able to them.

“In this en­vi­ron­ment, what­ev­er you can get, get,” Com­mit­tee chair Arnold Mon­to said.

J&J work­ing on vac­cine for vari­ants, tri­al sched­uled for sum­mer

This week, Mod­er­na an­nounced it would be­gin test­ing a mod­i­fied ver­sion of their mR­NA vac­cine to tack­le the vac­cine-re­sis­tant B1.351 vari­ant that popped up in South Africa. Pfiz­er said it would test giv­ing peo­ple an ex­tra boost of its orig­i­nal vac­cine to ac­com­plish the same.

J&J re­vealed at the ad­comm that they, too, have been work­ing on a mod­i­fied vac­cine to tack­le emerg­ing vari­ants.

The com­pa­ny didn’t re­veal much de­tail, in­clud­ing how they mod­i­fied the vac­cine or if they were tar­get­ing the same B1.351 vari­ant, but Jo­han van Hoof said they would be­gin test­ing a new con­struct in the sum­mer. The FDA has said they would al­low mod­i­fied vac­cines for vari­ants to be au­tho­rized af­ter quick im­muno­log­i­cal stud­ies that track whether the vac­cine elic­its an­ti­bod­ies against the new vari­ant.

4:15 J&J faces ques­tions on old­er adults, asymp­to­matic in­fec­tion, long-term im­mu­ni­ty

The FDA ad­comm has ad­vanced to the free-for-all ques­tion stage of the hear­ing and, as they did for Mod­er­na and Pfiz­er, com­mit­tee mem­bers are rais­ing ques­tions about the lin­ger­ing is­sues sur­round­ing the vac­cine.

In J&J’s case, one of those un­knowns is a group of par­tic­i­pants who ap­peared to re­spond worse to the vac­cine: those over 60 with co­mor­bidi­ties. In that group, the vac­cine was on­ly 42% ef­fec­tive at stop­ping dis­ease start­ing 28 days af­ter vac­ci­na­tion.

Both J&J and the FDA avoid­ed mak­ing any con­clu­sions about the num­ber, cau­tion­ing that there weren’t many peo­ple in that sub­group and it could just be a re­sult of a too-small sam­ple size. Still, Stan­ley Perl­man, a coro­n­avirus ex­pert at the Uni­ver­si­ty of Iowa, ques­tioned whether peo­ple in that group who re­ceive the shot will feel like they’re re­ceiv­ing a sec­ond-class vac­cine. (Mod­er­na and Pfiz­er both saw around 90% in old­er adults.)

“Peo­ple who re­ceive this will feel like they’re get­ting a vac­cine that doesn’t work as well,” Perl­man said. “We don’t want to have two class­es of par­tic­i­pants and feel like we’re in­creas­ing health in­equities.”

J&J’s Jo­han van Hoof not­ed in re­sponse that the vac­cine was more than 60% ef­fec­tive in that group be­tween day 14 and 28 and that the vac­cine still ap­peared able to pro­tect against se­vere dis­ease, in­clud­ing death. The dif­fer­ence could just be a re­sult of the place­bo group.

“There’s no ev­i­dence of sta­tis­ti­cal sig­nif­i­cance,” he said.

Mem­bers al­so asked about how long pro­tec­tion lasts and how ef­fec­tive it is against asymp­to­matic in­fec­tion. These ques­tions al­so loomed over the Pfiz­er or Mod­er­na for vac­cine, al­though they dif­fer for the J&J vac­cine in a cou­ple ways.

For one, J&J — un­like Pfiz­er and Mod­er­na — has al­ready col­lect­ed da­ta on asymp­to­matic in­fec­tion from about 1,500 par­tic­i­pants in both the place­bo and treat­ment arms, of­fer­ing pre­lim­i­nary da­ta that the vac­cine can re­duce asymp­to­matic in­fec­tion by around 70%. An ac­tu­al an­swer, though, may lag sig­nif­i­cant­ly: J&J won’t make the fi­nal cal­cu­la­tion un­til they have 6 months fol­lowup on 15,000 par­tic­i­pants.

The tech­nol­o­gy be­hind J&J’s vac­cine al­so changes the cal­cu­lus for the long-term re­sponse. J&J us­es a harm­less ade­n­ovirus to de­liv­er a gene for the coro­n­avirus spike pro­tein. But each time a per­son is ex­posed to that ade­n­ovirus, they de­vel­op an­ti­bod­ies against it — an­ti­bod­ies that might pre­vent boost­er shots from restor­ing im­mu­ni­ty if it wanes in sub­se­quent years.

Van Hoof, how­ev­er, said they ex­pect pro­tec­tion to last at least one to two years. And in tri­als for Ebo­la and HIV vac­cines that use the same plat­form, they had lit­tle trou­ble up­ping an­ti­body lev­els with shots in sub­se­quent years.

“It seems to have no prob­lem at all to get that boost­er re­sponse,” he said.

J&J is al­so test­ing a two-dose vac­cine. What hap­pens if it’s more ef­fec­tive?

J&J has spent the day tout­ing the da­ta be­hind their Covid-19 vac­cine, but one ad­vi­sor point­ed that, in a few months, an­oth­er batch of da­ta could force them in­to a cu­ri­ous dilem­ma.

J&J was the on­ly ma­jor vac­cine de­vel­op­er to at­tempt to pro­duce a sin­gle-dose vac­cine, a huge as­set when try­ing to rapid­ly in­oc­u­late the world against an on­go­ing pub­lic health threat, but they hedged their bets. Along­side their main Phase III tri­al, they al­so launched an­oth­er that would test two dos­es, each spaced two months apart.

Re­sults from the first tri­al are in: The vac­cine is 66% ef­fec­tive at pre­vent­ing mild ill­ness and 85% ef­fec­tive against se­vere dis­ease. As both the FDA and J&J have ar­gued, that’s enough to pro­vide a ma­jor weapon in the fight to bring Covid-19 un­der con­trol.

The sec­ond tri­al hasn’t read out yet, though. What hap­pens if it turns out that two dos­es are more ef­fec­tive than one?

“If we move for­ward with this vac­cine and find that with two dos­es we have a bet­ter clin­i­cal re­sponse, does this then be­come a two dose vac­cine?” Paul Of­fit, di­rec­tor of the Vac­cine Ed­u­ca­tion Cen­ter at the Chil­dren’s Hos­pi­tal of Philadel­phia, asked. If pos­i­tive da­ta even­tu­al­ly come in, should peo­ple who get the vac­cine in the com­ing weeks “come back for a sec­ond dose?”

J&J vac­cine ex­ec­u­tive Jo­han van Hoof didn’t di­rect­ly an­swer the ques­tion but he tout­ed re­peat­ed­ly the po­ten­tial pub­lic health ben­e­fits of a sin­gle-dose shot.

“In the sit­u­a­tion of an out­break, in a rag­ing epi­dem­ic, the big chal­lenge is to get the epi­dem­ic un­der con­trol,” Hoof said. “And that is where a sin­gle-dose vac­cine with rapid on­set of pro­tec­tion is high­ly pre­ferred.”

Of­fit agreed, but he said J&J may face a mes­sag­ing prob­lem if peo­ple hear that a sec­ond dose will be more ef­fec­tive.

1:26 New case re­port means ana­phy­lax­is con­cerns aren’t go­ing away

When the UK and the US au­tho­rized the Pfiz­er and Mod­er­na vac­cines and a tiny hand­ful of re­cip­i­ents de­vel­oped ana­phy­lac­tic re­ac­tions, re­searchers the­o­rized that the cul­prit may have been the lipid nanopar­ti­cle — the tiny bub­ble of fat used to en­case and de­liv­er mR­NA in­to cells.

Macaya Douogu­ih

At the FDA hear­ing, though, J&J’s head of med­ical af­fairs Macaya Douogu­ih re­vealed that on Wednes­day, the com­pa­ny was in­formed that one of the par­tic­i­pants in a new open-la­bel study in South Africa went in­to ana­phy­lac­tic shock af­ter re­ceiv­ing a dose of their vac­cine, which us­es a dif­fer­ent tech­nol­o­gy that doesn’t in­volve lipid nanopar­ti­cles.

While se­ri­ous, ana­phy­lac­tic re­ac­tions are both ex­cep­tion­al­ly rare (about 2.5 per mil­lion for Mod­er­na and 11.1 per mil­lion for Pfiz­er, ac­cord­ing to a re­cent JA­MA study) and easy to han­dle: Re­cip­i­ents are mon­i­tored for 15 min­utes af­ter in­jec­tion and, in the un­like­ly event there’s a re­ac­tion, giv­en ep­i­neph­rin.

Still, the new re­port means the is­sue is one doc­tors and of­fi­cials will have to con­sid­er for per­haps all vac­cines and for the lengthy re­main­der of the glob­al vac­ci­na­tion ef­fort.

11:10 Will vari­ants im­pede a long-sought goal for Covid-19 re­search?

The Covid-19 vac­cine tri­als have been an all-but un­mit­i­gat­ed suc­cess, lay­ing the ba­sis for vac­cines that have since brought the virus to heel in lo­ca­tions where they’ve been rolled out. But they are al­so long and la­bo­ri­ous and will be in­creas­ing­ly dif­fi­cult to run as more peo­ple be­come el­i­gi­ble for an au­tho­rized vac­cine and un­will­ing to risk get­ting a place­bo.

That’s why vac­ci­nol­o­gists have been work­ing all year to es­tab­lish an im­mune cor­re­late of pro­tec­tion — a pre­cise mix of an­ti­bod­ies that, with a sim­ple blood test, can de­ter­mine whether some­one will be pro­tect­ed. It’s how new flu vac­cines are ap­proved and it could al­low new Covid-19 vac­cines to reach mar­ket at a far brisker pace.

Adam Mac­Neil

As CDC epi­demi­ol­o­gist Adam Mac­Neil pre­sent­ed on new vari­ants, though, FDA com­mit­tee mem­bers ques­tioned whether mu­tat­ed ver­sions of the virus could jeop­ar­dize that goal. If new vari­ants, such as the B1.351 one that emerged in South Africa, es­cape the mix of an­ti­bod­ies in­duced by cur­rent vac­cines, wouldn’t that make it dif­fi­cult to find a sin­gle stan­dard for how many and what kind of an­ti­bod­ies of­fers pro­tec­tion?

“It may be a mov­ing tar­get,” Mac­Neil said.

It’s a ques­tion, Mac­Neil said, that will loom over the com­ing years as re­searchers mon­i­tor a virus that is not go­ing to van­ish and try to de­ter­mine whether and how to up­date vac­cines.

“Will we need an­nu­al up­dates like in­fluen­za?” he said. “Will we need an­nu­al up­dates every five years? Or will we have broad enough pro­tec­tion to in essence use a steady-state vac­cine?”

10:21 Pan­elists ques­tion EUA end­points as new vari­ants emerge

Greet­ings from the first tech­ni­cal dif­fi­cul­ties of the FDA ad­vi­so­ry com­mit­tee for J&J’s Covid-19 shot.

Arnold Mon­to

The au­dio went out on the live stream at about 9:30am and af­ter about 5 min­utes of un­halt­ed dis­cus­sion, they sent view­ers to a “time for a break” page. While they sort that out — oc­ca­sion­al­ly act­ing chair Arnold Mon­to’s voice breaks through the in­die hold mu­sic, so could be soon — we’ll fill you in on the hear­ing so far.

The first hour or so of an ad­comm is large­ly lo­gis­tics, in­clud­ing in­tro­duc­ing the com­mit­tee and out­lin­ing the le­gal ba­sis for emer­gency use au­tho­riza­tion mem­bers. Be­fore the au­dio dropped, though, a few com­mit­tee mem­bers were able to ask ques­tions and they cen­tered in part over what the right end­points should be for an EUA.

Over the sum­mer and fall, the FDA is­sued guide­lines that any vac­cine de­vel­op­er would have to prove their vac­cine was at least 50% ef­fec­tive at stop­ping dis­ease and fol­low tri­al par­tic­i­pants for at least two months for safe­ty. With two mR­NA vac­cines al­ready au­tho­rized and huge­ly ef­fec­tive, Mon­to asked, have those stan­dards changed at all?

Cody Meiss­ner

Cody Meiss­ner, head of pe­di­atric in­fec­tious dis­ease at Tufts Med­ical Cen­ter, put the ques­tion dif­fer­ent­ly: J&J’s vac­cine proved less ef­fec­tive — 66% com­pared to 95% — at pre­vent­ing mild dis­ease than the mR­NA vac­cines, but they con­duct­ed the tri­al at a time when new vari­ants of the virus had arisen, in­clud­ing a vari­ant in South Africa that has proven vac­cine-re­sis­tant. At the same time, the J&J vac­cine still proved high­ly ef­fec­tive at pre­vent­ing hos­pi­tal­iza­tion and death.

“Be­cause the strains of SARS-CoV-2 that are cir­cu­lat­ing now may be some­what dif­fer­ent than the ones that were cir­cu­lat­ing dur­ing the tri­als for the mes­sen­ger RNA, and so the ef­fi­ca­cy at pre­vent­ing rel­a­tive­ly mild or even mod­er­ate dis­ease might be dif­fer­ent,” Meiss­ner said. “But all the vac­cine seem to be equal­ly ef­fec­tive same for se­vere dis­ease and death. Has the FDA con­sid­ered that per­haps dif­fer­ent end­points should be con­sid­ered in terms of grant­i­ng an EUA in the fu­ture, as new vac­cines ap­ply for EUA?”

For now, the an­swer is no. Maria Al­lende, an FDA med­ical of­fi­cer, said the FDA would keep the cur­rent end­points un­til they can find im­mune cor­re­late of pro­tec­tion — a blood test to see if par­tic­i­pants have the right mix­ture of an­ti­bod­ies to pro­tect against dis­ease — and they would use sur­veil­lance and re­al-world mon­i­tor­ing mech­a­nisms to track how well the vac­cines work against new vari­ants.

The stan­dards for full ap­proval have not changed ei­ther, she said in re­sponse to an­oth­er ques­tion. The FDA would like 6 months of fol­lowup on tri­al par­tic­i­pants to ful­ly ap­prove a vac­cine, a bench­mark that would put Mod­er­na and Pfiz­er on the path to an ap­proval ap­pli­ca­tion in the next cou­ple of months.

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