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.

M&A: a crit­i­cal dri­ver for sus­tain­able top-line growth in health­care

2021 saw a record $600B in healthcare M&A activity. In 2022, there is an anticipated slowdown in activity, however, M&A prospects remain strong in the medium to long-term. What are future growth drivers for the healthcare sector? Where might we see innovations that drive M&A? RBC’s Andrew Callaway, Global Head, Healthcare Investment Banking discusses with Vito Sperduto, Global Co-Head, M&A.

15 LGBTQ lead­ers in bio­phar­ma; Paul Stof­fels’ Gala­pa­gos re­vamp; As­traZeneca catch­es up in AT­TR; 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.

A return to in-person conferences also marks a return to on-the-ground reporting. My colleagues Beth Synder Bulik and Nicole DeFeudis were on-site at Cannes Lions, bringing live coverage of pharma’s presence at the ad festival — accompanied by photos from Clara Bui, our virtual producer, that bring you right to the scene. You can find a recap (and links to all the stories) below.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 144,300+ biopharma pros reading Endpoints daily — and it's free.

Abortion-rights protesters regroup and protest following Supreme Court's decision to overturn Roe v. Wade. (AP Photo/Gemunu Amarasinghe)

Fol­low­ing SCO­TUS de­ci­sion to over­turn abor­tion pro­tec­tions, AG Gar­land says states can't ban the abor­tion pill

Following the Supreme Court’s historic decision on Friday to overturn Americans’ constitutional right to an abortion after almost 50 years, Attorney General Merrick Garland sought to somewhat reassure women that states will not be able to ban the prescription drug sometimes used for abortions.

Following the decision, the New England Journal of Medicine also published an editorial strongly condemning the reversal, saying it “serves American families poorly, putting their health, safety, finances, and futures at risk.”

AstraZeneca's new Evusheld direct to consumer campaign aims to reach more immunocompromised patients.

As­traZeneca de­buts first con­sumer cam­paign for its Covid-19 pro­phy­lac­tic Evusheld — and a first for EUA drugs

AstraZeneca’s first consumer ad for Evusheld is also a first for drugs that have been granted emergency use authorizations during the pandemic.

The first DTC ad for a medicine under emergency approval, the Evusheld campaign launching this week aims to raise awareness among immunocompromised patients — and spur more use.

Evusheld nabbed emergency authorization in December, however, despite millions of immunocompromised people looking for a solution and now more widespread availability of the drug.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 144,300+ biopharma pros reading Endpoints daily — and it's free.

Sanofi, GSK tout 72% Omi­cron ef­fi­ca­cy in PhI­II tri­al of next-gen, bi­va­lent shot — with an eye to year-end roll­out

Sometimes, being late can give you an advantage.

That’s what Sanofi and GSK are trying to say as the Big Pharma partners report positive results from a late-stage trial of their next-gen bivalent Covid-19 vaccine, which was designed to protect against both the original strain of the SARS-CoV-2 virus and the Beta variant. Specifically, against Omicron, they note, the vaccine delivered 72% efficacy in all adults and 93.2% in those previously infected.

Rwanda president Paul Kagame and BioNTech CEO Uğur Şahin (via BioNTech)

BioN­Tech breaks ground on first mR­NA vac­cine man­u­fac­tur­ing fa­cil­i­ty in Africa

Covid vaccine access to lower- and middle-income nations has been a concern during the length of the pandemic, but BioNTech is now pushing forward with plans to increase vaccine access for Africa.

Construction work has kicked off for an mRNA manufacturing facility in Kigali, Rwanda. According to BioNTech, the facility, dubbed the African modular mRNA manufacturing facility, has a target for the first set of manufacturing tools to be delivered to the site by the end of this year.

GSK says its drug for chron­ic hep B could ‘lead to a func­tion­al cure’ — but will it be alone or in com­bi­na­tion?

GSK, newly branded and soon-to-be demerged, shared interim results from its Phase II trial on its chronic hepatitis B treatment, one that it says has the “potential to lead to a functional cure.”

At a presentation at the EASL International Liver Congress, GSK shared that in around 450 patients who received its hep B drug bepirovirsen for 24 weeks, just under 30% had hepatitis B surface antigen and viral DNA levels that were too low to detect.

Stéphane Bancel (AP Photo/Charles Krupa)

Mod­er­na to se­cure a UK pres­ence with $1B+ in new man­u­fac­tur­ing and R&D fa­cil­i­ties

As Moderna keeps up the fight against Covid-19, recently winning authorization in the US for children under the age of five, the company is also looking to make a serious investment in the UK.

According to the UK government, Moderna will be looking to establish a vaccine research center and a manufacturing site for a series of vaccines.

Moderna will establish this new mRNA Innovation and Technology Centre to develop mRNA vaccines for a wide range of respiratory diseases, including Covid-19.

De­spite a slow start to the year for deals, PwC pre­dicts a flur­ry of ac­tiv­i­ty com­ing up

Despite whispers of a busy year for M&A, deal activity in the pharma space is actually down 30% on a semi-annualized basis, according to PwC’s latest report on deal activity. But don’t rule out larger deals in the second half of the year, the consultants said.

PwC pharmaceutical and life sciences consulting solutions leader Glenn Hunzinger expects to see Big Pharma companies picking up earlier stage companies to try and fill pipeline gaps ahead of a slew of big patent cliffs. Though a bear market continues to maul the biotech sector, Hunzinger said recent deals indicate that pharma companies are still paying above current trading prices.