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.

BY­OD Best Prac­tices: How Mo­bile De­vice Strat­e­gy Leads to More Pa­tient-Cen­tric Clin­i­cal Tri­als

Some of the most time- and cost-consuming components of clinical research center on gathering, analyzing, and reporting data. To improve efficiency, many clinical trial sponsors have shifted to electronic clinical outcome assessments (eCOA), including electronic patient-reported outcome (ePRO) tools.

In most cases, patients enter data using apps installed on provisioned devices. At a time when 81% of Americans own a smartphone, why not use the device they rely on every day?

Voting in the 2020 election (AP Images)

The right to vote is fun­da­men­tal — a let­ter from biotech­nol­o­gy in­dus­try lead­ers

Biotech Voices is a collection of exclusive opinion editorials from some of the leading voices in biopharma on the biggest industry questions today. Think you have a voice that should be heard? Reach out to senior editors Kyle Blankenship and Amber Tong.

We oppose all attempts to introduce laws that reduce the rights of US citizens to vote or that restrict them from exercising that right. The right to vote is fundamental to democracy. States that have enacted, or are proposing to enact, legislation to restrict voting are undermining our democracy and posing a threat to our nation. As leaders of the life sciences industry, we stand for what we believe is right for our country, our enterprises, our employees and those who benefit from our work. We join the first groups of business leaders who have challenged these laws and will continue to make our collective voices heard on this matter.

UP­DAT­ED: J&J paus­es vac­cine roll­out as feds probe rare cas­es of blood clots

The FDA and CDC have jointly decided to stop administering J&J’s Covid-19 vaccine after reviewing data involving six reported US cases of a rare and severe type of blood clot in individuals after receiving the vaccine.

CDC will convene a meeting of its Advisory Committee on Immunization Practices on Wednesday to further review these cases and assess their potential significance. “FDA will review that analysis as it also investigates these cases. Until that process is complete, we are recommending a pause in the use of this vaccine out of an abundance of caution,” Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research and Anne Schuchat, Principal Deputy Director of the CDC, said in a joint statement Tuesday morning.

Pascal Soriot (AstraZeneca via YouTube)

Af­ter be­ing goad­ed to sell the com­pa­ny, Alex­ion's CEO set some am­bi­tious new goals for in­vestors. Then Pas­cal So­ri­ot came call­ing

Back in the spring of 2020, Alexion $ALXN CEO Ludwig Hantson was under considerable pressure to perform and had been for months. Elliott Advisers had been applying some high public heat on the biotech’s numbers. And in reaching out to some major stockholders, one thread of advice came through loud and clear: Sell the company or do something dramatic to change the narrative.

In the words of the rather dry SEC filing that offers a detailed backgrounder on the buyout deal, Alexion stated: ‘During the summer and fall of 2020, Alexion also continued to engage with its stockholders, and in these interactions, several stockholders encouraged the company to explore strategic alternatives.’

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Near­ly a year af­ter Au­den­tes' gene ther­a­py deaths, the tri­al con­tin­ues. What hap­pened re­mains a mys­tery

Natalie Holles was five months into her tenure as Audentes CEO and working to smooth out a $3 billion merger when the world crashed in.

Holles and her team received word on the morning of May 5 that, hours before, a patient died in a trial for their lead gene therapy. They went into triage mode, alerting the FDA, calling trial investigators to begin to understand what happened, and, the next day, writing a letter to alert the patient community so they would be the first to know. “We wanted to be as forthright and transparent as possible,” Holles told me late last month.

The brief letter noted two other patients also suffered severe reactions after receiving a high dose of the therapy and were undergoing treatment. One died a month and a half later, at which point news of the deaths became public, jolting an emergent gene therapy field and raising questions about the safety of the high doses Audentes and others were now using. The third patient died in August.

“It was deeply saddening,” Holles said. “But I was — we were — resolute and determined to understand what happened and learn from it and get back on track.”

Eleven months have now passed since the first death and the therapy, a potential cure for a rare and fatal muscle-wasting disease called X-linked myotubular myopathy, is back on track, the FDA having cleared the company to resume dosing at a lower level. Audentes itself is no more; last month, Japanese pharma giant Astellas announced it had completed working out the kinks of the $3 billion merger and had restructured and rebranded the subsidiary as Astellas Gene Therapies. Holles, having successfully steered both efforts, departed.

Still, questions about precisely what led to the deaths of the 3 boys still linger. Trial investigators released key details about the case last August and December, pointing to a biological landmine that Audentes could not have seen coming — a moment of profound medical misfortune. In an emerging field that’s promised cures for devastating diseases but also seen its share of safety setbacks, the cases provided a cautionary tale.

Audentes “contributed in a positive way by giving a painful but important example for others to look at and learn from,” Terry Flotte, dean of the UMass School of Medicine and editor of the journal Human Gene Therapy, told me. “I can’t see anything they did wrong.”

Yet some researchers say they’re still waiting on Astellas to release more data. The company has yet to publish a full paper detailing what happened, nor have they indicated that they will. In the meantime, it remains unclear what triggered the events and how to prevent them in the future.

“Since Audentes was the first one and we don’t have additional information, we’re kind of in a holding pattern, flying around, waiting to figure out how to land our vehicles,” said Jude Samulski, professor of pharmacology at UNC’s Gene Therapy Center and CSO of the gene therapy biotech AskBio, now a subsidiary of Bayer.

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Launched by MIT grads, a small start­up gets $20M to back a ro­bot­ics rev­o­lu­tion in cell ther­a­py man­u­fac­tur­ing

As co-director of an experimental cellular therapy process development and manufacturing group at UCSF specializing in T cell therapies for autoimmune conditions, Jonathan Esensten has learned a lot about the challenges involved when his group hand-fashions a cell therapy. Esensten — who was a postdoc in Wendell Lim’s lab and counts the legendary Jeffrey Bluestone as a mentor — gives them all high marks at being great at what they do, but time and again there are variations in the treatments they construct.

Anand Shah (FDA)

For­mer head of FDA’s med­ical and sci­en­tif­ic af­fairs on Covid: ‘FDA has nev­er been test­ed like this’

Anand Shah has served the American public in a unique way, crisscrossing over the last two administrations between serving as an attending radiation oncologist focused on prostate cancer at NIH, serving as CMO at the Center for Medicare and Medicaid Innovation, and most recently, leading the FDA’s operations on medical and scientific affairs from within the commissioner’s office.

Shah, who stepped down from the FDA in January, caught up with Endpoints News in a phone interview on Tuesday afternoon, offering his thoughts on the agency’s latest decision to pause the J&J vaccinations in the US, and reflecting on his time at an agency during this once-in-a-lifetime pandemic.

Patrizia Cavazzoni, new CDER director

Pa­trizia Cavaz­zoni named per­ma­nent di­rec­tor of CDER, adding to ques­tions around where Wood­cock will end up

Patrizia Cavazzoni on Monday became the permanent director of the FDA’s Center for Drug Evaluation and Research, which puts to rest the idea that Janet Woodcock, Cavazzoni’s predecessor, might return to lead CDER if she isn’t made permanent commissioner.

Woodcock, who’s currently serving as acting commissioner and principal medical advisor to the commissioner, a position she was detailed to last year, may not make the move to permanent commissioner because of lingering questions from Senate Democrats. She previously served as director of CDER since 1994. Cavazzoni took over as acting director of CDER when Woodcock moved over to Operation Warp Speed to run the therapeutics side of the Trump-era program.

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Barbara Weber, Tango Therapeutics CEO (Tango)

It takes two to Tan­go: The biotech us­ing CRISPR to dis­cov­er new can­cer gene tar­gets rides a $353M SPAC deal to Nas­daq

Editor’s note: Interested in following biopharma’s fast-paced IPO market? You can bookmark our IPO Tracker here.

The latest biotech-SPAC deal has arrived, and it’s dancing its way to Nasdaq to the tune of several hundred million dollars.

Tango Therapeutics and its CRISPR-focused search for new cancer genes is reverse merging with Boxer Capital’s blank-check company, the biotech announced Wednesday morning. With a spotlight on three lead programs, Tango expects total proceeds to equal about $353 million in the deal, which includes the roughly $167 million held in the SPAC and an additional $186 million in PIPE financing.