President Biden and Pfizer CEO Albert Bourla (Patrick Semansky/AP Images)

Chaot­ic ad­comm sees Pfiz­er/BioN­Tech boost­ers re­ject­ed for gen­er­al pop­u­la­tion, but rec­om­mend­ed for old­er and high-risk pop­u­la­tions

With just days be­fore Pres­i­dent Joe Biden’s Covid-19 boost­er roll­out is set to go in­to ef­fect, an FDA ad­vi­so­ry com­mit­tee ap­peared on the verge of not rec­om­mend­ing boost­ers for any­one in the US be­fore a last-minute change of word­ing laid the ground­work for old­er adults to have ac­cess to a third dose.

The FDA’s ad­comm on Vac­cines and Re­lat­ed Bi­o­log­i­cal Prod­ucts (VRB­PAC) round­ly re­ject­ed Pfiz­er/BioN­Tech boost­er shots for all in­di­vid­u­als old­er than 16 by a 16-2 vote Fri­day af­ter­noon. Soon af­ter, how­ev­er, the agency posed com­mit­tee mem­bers a new ques­tion lim­it­ing boost­er use to the 65-and-old­er pop­u­la­tion and in­di­vid­u­als at high risk of dis­ease due to oc­cu­pa­tion­al ex­po­sure or co­mor­bidi­ties.

That ques­tion, com­ing rough­ly 45 min­utes af­ter the first, passed through the ad­comm with a unan­i­mous 18-0 vote. This vote cen­tered on an emer­gency use au­tho­riza­tion — not the sup­ple­men­tal BLA for which Pfiz­er had ap­plied.

And at the end of the hear­ing, CBER di­rec­tor Pe­ter Marks asked the pan­el to take an “in­for­mal poll” on whether health-care work­ers and oth­ers at high risk of “oc­cu­pa­tion­al ex­po­sure” be in­clud­ed in the EUA. Here, the pan­el al­so gave a unan­i­mous 18-0 yes.

Af­ter the votes, Pfiz­er vac­cine chief Kathrin Jansen said in a state­ment that the com­pa­ny would con­tin­ue to push for boost­ers in the gen­er­al pop­u­la­tion.

“These da­ta, and the larg­er body of sci­en­tif­ic ev­i­dence pre­sent­ed at the meet­ing, un­der­score our be­lief that boost­ers will be a crit­i­cal tool in the on­go­ing ef­fort to con­trol the spread of this virus,” Jansen said in an emailed state­ment to End­points News. “We thank the com­mit­tee for their thought­ful re­view of the da­ta and will work with the FDA fol­low­ing to­day’s meet­ing to ad­dress the com­mit­tee’s ques­tions, as we con­tin­ue to be­lieve in the ben­e­fits of a boost­er dose for a broad­er pop­u­la­tion.”

Sev­er­al ad­comm mem­bers not­ed through­out the dis­cus­sion pe­ri­od that they’d be open to rec­om­mend­ing boost­ers for small­er high-risk pop­u­la­tions, prompt­ing pan­el chair Arnold Mon­to to ask Marks for mul­ti­ple clar­i­fi­ca­tions on the orig­i­nal, broad vot­ing ques­tion. The ques­tion, re­leased late Thurs­day night, asked whether or not the safe­ty and ef­fi­ca­cy da­ta from Pfiz­er/BioN­Tech’s orig­i­nal Phase III study “sup­port­ed ap­proval” of a boost­er at least six months af­ter the sec­ond dose in those aged 16 and up.

But Mon­to asked if Marks would al­low pan­el mem­bers to con­sid­er da­ta from oth­er re­al-world stud­ies in their votes, to which Marks said the com­mit­tee would be al­lowed to con­sid­er the “to­tal­i­ty of the da­ta.” Then, Mon­to want­ed to know if the ques­tion could be mod­i­fied to al­low com­mit­tee mem­bers to vote on a nar­row­er pop­u­la­tion.

Marks once again an­swered in the af­fir­ma­tive but, in an ex­tra­or­di­nary ex­change, re­ceived sig­nif­i­cant push­back from top vac­cine of­fi­cial Mar­i­on Gru­ber who not­ed that Pfiz­er’s sub­mis­sion cov­ered all in­di­vid­u­als old­er than 16. Gru­ber, along with an­oth­er top vac­cine staffer, Philip Krause, an­nounced their in­tent to re­tire last month af­ter rais­ing con­cerns with boost­ers in the Lancet.

Mon­to then al­lowed Pfiz­er to make a five-minute clos­ing state­ment that was not on the agen­da, in which com­pa­ny ex­ecs pushed for the com­mit­tee to vote on the orig­i­nal ques­tion.

Ob­servers crit­i­cized the FDA in the im­me­di­ate wake of the first vote, pos­ing what they said was an in­flex­i­ble ques­tion giv­en some da­ta has shown the ben­e­fits of boost­ers out­weigh the risk in old­er pop­u­la­tions. Scripps Re­search di­rec­tor Er­ic Topol blast­ed the agency, say­ing the first ques­tion “was set up to fail” in es­sen­tial­ly ask­ing for da­ta that are not yet avail­able.

Through­out the af­ter­noon, pan­elists had ex­pressed se­vere reser­va­tions about rec­om­mend­ing boost­ers for every­one old­er than 16, par­tic­u­lar­ly giv­en the un­known safe­ty risks in young boys and men with re­gards to my­ocardi­tis. It’s an is­sue that harkened back to the orig­i­nal vac­cine ad­comm as well, when pan­elists took is­sue with ap­prov­ing vac­cines for 16- and 17-year-olds.

“I was struck by the FDA’s com­ments on the to­tal­i­ty of da­ta giv­en there’s more da­ta com­ing soon on safe­ty for my­ocardi­tis,” pan­el mem­ber Hay­ley Gans said af­ter the first vote. “It feels like a missed op­por­tu­ni­ty when they con­sid­er these [datasets] large enough even when we have da­ta we could have looked at … it feels like we’re mak­ing de­ci­sions when there’s still da­ta out there.”

Af­ter the first vote con­clud­ed with a re­sound­ing no, FDA of­fi­cials re­turned to com­mit­tee mem­bers with a new ques­tion. Rather than fo­cus on the en­tire gen­er­al pop­u­la­tion, reg­u­la­tors posed the fol­low­ing ques­tion:

Based on the to­tal­i­ty of sci­en­tif­ic ev­i­dence avail­able, in­clud­ing the safe­ty and ef­fec­tive­ness da­ta from clin­i­cal tri­al C4591001, do the known and po­ten­tial ben­e­fits out­weigh the known and po­ten­tial risks of a Pfiz­er-BioN­Tech Covid-19 vac­cine boost­er dose ad­min­is­tered at least 6 months af­ter com­ple­tion of the pri­ma­ry se­ries for use in:

a) In­di­vid­u­als 65 years of age and old­er, and

b) In­di­vid­u­als at high risk of se­vere Covid-19

It’s here where the ma­jor­i­ty of pan­elists seemed to agree, giv­ing the EUA their thumbs up rec­om­men­da­tion.

The ad­comm start­ed off bright and ear­ly at 8:30 a.m. East­ern, with Mon­to wel­com­ing view­ers to the livestream. Af­ter a brief in­tro­duc­tion he soon hand­ed things off to Marks who, in a strik­ing move, di­rect­ed pan­el mem­bers to fo­cus con­ver­sa­tions on the sci­ence rather than con­cerns over vac­cine eq­ui­ty or “op­er­a­tional is­sues re­lat­ed to a boost­er cam­paign.”

Marks’ com­ments came against the back­drop of Gru­ber and Krause’s res­ig­na­tions. The two al­so co-au­thored an ar­ti­cle in the Lancet this week as­sert­ing boost­er dos­es for the gen­er­al pop­u­la­tion are not ap­pro­pri­ate at this stage in the pan­dem­ic, and Gru­ber — who spoke dur­ing the in­tro­duc­tion — not­ed this would like­ly be her last ad­comm ap­pear­ance.

An­oth­er co-au­thor to that pa­per, British sta­tis­ti­cian Jonathan Sterne, gave a pre­sen­ta­tion ear­ly in the ses­sion on the top­ic of “con­found­ables,” or vari­ables that can in­tro­duce or pre­dict both vac­ci­na­tion and Covid-19 out­comes in re­al-world stud­ies. Sterne’s dis­cus­sion drew wide praise among ob­servers on so­cial me­dia, rais­ing ques­tions over how dif­fi­cult it is to de­ter­mine whether wan­ing vac­cine im­mu­ni­ty is pri­mar­i­ly a re­sult of the shots be­com­ing less ef­fec­tive or the Delta vari­ant’s surge.

Sand­wich­ing Sterne were da­ta pre­sen­ta­tions from the CDC and Is­raeli health of­fi­cials, who de­scribed how the pan­dem­ic had pro­gressed in their coun­tries. The Is­raeli pre­sen­ta­tion al­so in­clud­ed da­ta from re­al-world stud­ies dur­ing the coun­try’s Delta surge, which proved no­table giv­en the FDA’s writ­ten ques­tion to pan­el mem­bers asked sole­ly about Pfiz­er’s Phase III study.

Soon af­ter came the heavy hit­ters: Pfiz­er and the FDA. Much of the ar­gu­ments as­sert­ed here matched up with how they each in­ter­pret­ed the da­ta in the brief­ing doc­u­ments re­leased ear­li­er this week. In a mi­nor point of con­tention dur­ing the hear­ing, Mon­to cut off Pfiz­er’s pre­sen­ter who went over his al­lot­ted time when try­ing to re­it­er­ate find­ings from Is­raeli stud­ies.

Af­ter these pre­sen­ta­tions and the open com­ment pe­ri­od, pan­elists be­gan their Q&A ses­sion with Pfiz­er and the FDA. The first ques­tion de­liv­ered some fire­works, with Gru­ber giv­ing Krause the op­por­tu­ni­ty to ques­tion Pfiz­er on the sta­tis­ti­cal mod­els used in a re­al-world study in Is­rael.

Krause claimed there was a dis­crep­an­cy be­tween the ef­fi­ca­cy Pfiz­er re­port­ed us­ing a spe­cif­ic mod­el, which said ef­fi­ca­cy af­ter 8 months fell to 58% to 61%, but num­bers cal­cu­lat­ed through a dif­fer­ent math­e­mat­i­cal process us­ing cas­es per per­son-years re­sult­ed in 93% ef­fi­ca­cy. These dis­parate fig­ures, Krause said, came from the same num­ber of cas­es in a study by Cal­i­for­nia health care com­pa­ny Kaiser Per­ma­nente.

When giv­en time to re­spond, how­ev­er, Pfiz­er be­gan ex­pe­ri­enc­ing tech­ni­cal dif­fi­cul­ties. Ex­ecs from the Big Phar­ma os­ten­si­bly had three mi­cro­phone lines open at the same time, per the ad­comm’s tech­ni­cal mod­er­a­tor, prompt­ing an un­sched­uled break to fix the is­sue. Af­ter the feed re­turned, Mon­to moved the pan­el on to the next ques­tion.

Pan­elists con­tin­ued pep­per­ing Pfiz­er with ques­tions about the risks of my­ocardi­tis in younger pa­tients and whether Pfiz­er should tai­lor its boost­er shots to spe­cif­ic vari­ants. Ques­tions al­so arose about how Is­raeli of­fi­cials have clas­si­fied se­vere Covid-19, with the CDC pre­sen­ter say­ing they use a loos­er de­f­i­n­i­tion than the Unit­ed States.

Then things moved to the dis­cus­sion pe­ri­od when things start­ed to grow more chaot­ic. Ul­ti­mate­ly, the pan­el land­ed on rec­om­mend­ing an EUA for in­di­vid­u­als 65 and old­er and at high risk for se­vere Covid-19. The ball now moves back to the FDA’s court, and it’s not im­me­di­ate­ly clear how long it will take for the agency to make an EUA de­ci­sion.

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

The Fac­tors Dri­ving a Rapid Evo­lu­tion of Gene & Cell Ther­a­py and CAR-T Clin­i­cal Re­search in APAC

APAC is the fastest growing region globally for cell & gene therapy trials representing more than a third of all cell & gene studies globally, with China leading in the region. 

APAC is the leading location globally for CAR-T trials with China attracting ~60% of all CAR-T trials globally between 2015-2022. The number of CAR-T trials initiated by Western companies has rapidly increased in recent years (current CAGR of about 60%), with multiple targets being explored including CD19, CD20, CD22, BCMA, CD30, CD123, CD33, CD38, and CD138.

The End­points 11; blue­bird's $3M gene ther­a­py; Bio­gen tout new neu­ro da­ta; Harsh re­views for can­cer drugs; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Reading about John Carroll’s pick of biotech’s most promising startups has become a treasured tradition. If you ever get curious about previous classes of the Endpoints 11, you can find all of them (plus a number of our other regular specials) here.

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EMA warns of short­ages of two Boehringer heart drugs due to a spike in de­mand

The EMA is putting EU member states on alert over the shortage of two drugs that counter heart attacks due to an uptick in demand.

On Friday, the EMA sent out a warning that two Boehringer Ingelheim drugs are experiencing a shortage: Actilyse and Metalyse. The drugs are used as emergency treatments for adults experiencing acute myocardial infarction, or a heart attack, by dissolving blood clots that have formed in the blood vessels.

The End­points 11: The top pri­vate biotechs in pur­suit of new drugs. Push­ing the en­ve­lope with pow­er­ful new tech­nolo­gies

Right around the beginning of the year, we got a close-up look at what happens after a boom ripples through biotech. The crash of life sciences stocks in Q1 was heard around the world.

In the months since, we’ve seen the natural Darwinian down cycle take effect. Reverse mergers made a comeback, with more burned out shells to go public at a time IPOs and road shows are out of favor. And no doubt some of the more recent arrivals on the investing side of the business are finding greener pastures.

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Solicitor General Elizabeth Prelogar

Should SCO­TUS hear Am­gen's Repatha case? So­lic­i­tor gen­er­al says no

Back in April, Amgen said it was encouraged by the solicitor general’s anticipated review of its Supreme Court petition to rehear a Repatha patent case. They’re likely much less optimistic about the outcome now.

Solicitor General Elizabeth Prelogar wrote in a recent 27-page brief that Amgen’s arguments “lack merit and further review is not warranted.”

The case traces back to a suit filed in 2014 against Sanofi and Regeneron’s Praluent, which ended up beating Amgen’s PCSK9 blockbuster Repatha to market by a month just a year later.

Phil Sharp, Nobel Prize laureate (L), and John Carroll, Endpoints News co-CEO (via Michael Last)

The End­points 11: Fire­side chat with No­bel Prize lau­re­ate Phil Sharp

The following Q&A has been edited for length and clarity.

John Carroll:

We’ve had a chance to talk a little bit before here about some of the things that you’ve done. Just really remarkably, a lot of the things that you’ve done early in your career puts you in the path with some amazing science that has had an absolutely huge impact in terms of what we’re seeing now on drug development and some of the new technologies that are coming out here, and not only the new technologies, but also some of the most remarkable people ever.

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Petro Terblanche, Afrigen Biologics managing director (Kristin Palitza/picture-alliance/dpa/AP Images)

WHO-backed Afrigen plans a charge to­ward the clin­ic with Africa's first Covid-19 vac­cine

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Klick Health gath­ers biotech and phar­ma lu­mi­nar­ies to dis­cuss in­dus­try in­no­va­tions, in­vest­ments and fu­ture

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George Yancopoulos, chief scientist and cofounder of Regeneron, opened the conference responding to a question from Acorda CEO Ron Cohen about the spotlight on the industry during Covid and some of the “flak” biopharma has taken in the past.

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Though Moderna’s bivalent vaccine to counter the Omicron variant has cleared the initial hurdles in getting FDA authorization, the vaccine maker is moving on to the next step.

On Twitter, the company announced on Friday that it has filed a EUA for its bivalent vaccine for use in adolescents aged 12 through 17 and for smaller children aged six through 11.