The FDA re­leased brief­ing doc­u­ments this week from the agency and Pfiz­er each out­lin­ing their ar­gu­ments for to­day’s Covid-19 boost­er shot ad­comm, but one thing con­spic­u­ous­ly miss­ing was the ques­tion on which pan­el mem­bers would be vot­ing. But late Thurs­day night, reg­u­la­tors pub­lished that ques­tion.

Ad­comm mem­bers will be asked whether or not the safe­ty and ef­fi­ca­cy da­ta from Pfiz­er/BioN­Tech’s orig­i­nal Phase III study “sup­port ap­proval” of a boost­er shot at least six months af­ter the sec­ond dose in in­di­vid­u­als old­er than 16. The ques­tion no­tably ex­cludes the re­al-world da­ta from Is­rael and oth­er analy­ses that Pfiz­er and the Biden ad­min­is­tra­tion had said would be a cen­ter­piece of their ar­gu­ments for boost­ers.

It’s not im­me­di­ate­ly clear whether this ques­tion would be the on­ly one asked at the ad­comm, but the FDA had yet to up­date its web­site as of ear­ly Fri­day morn­ing.

Here’s the ex­act word­ing:

Do the safe­ty and ef­fec­tive­ness da­ta from clin­i­cal tri­al C4591001 sup­port ap­proval of a COMIR­NATY boost­er dose ad­min­is­tered at least 6 months af­ter com­ple­tion of the pri­ma­ry se­ries for use in in­di­vid­u­als 16 years of age and old­er? Please vote Yes or No.

Pfiz­er spent much of its 53-page brief­ing doc­u­ment on the var­i­ous ob­ser­va­tion­al stud­ies that have popped up dur­ing the Delta surge, show­ing the vac­cine’s pro­tec­tion against mild dis­ease wan­ing over time but re­main­ing very strong against se­vere Covid-19 and hos­pi­tal­iza­tion. The FDA’s brief­ing doc­u­ments, how­ev­er, spent on­ly two para­graphs ad­dress­ing those stud­ies, say­ing there is a lot that present “con­flict­ing con­clu­sions.”

The word­ing of the ques­tion dif­fers con­sid­er­ably from those asked in the orig­i­nal vac­cine ad­comms last year, be­fore any vac­cine had been au­tho­rized or ap­proved. Fri­day’s ques­tion fo­cus­es specif­i­cal­ly on sup­port­ing ap­proval, where­as the old­er ques­tions asked whether or not the ben­e­fits of the vac­cine out­weighed the risks.

It’s a phras­ing some out­side ob­servers strug­gled to in­ter­pret. Walid Gel­lad, di­rec­tor of the Uni­ver­si­ty of Pitts­burgh Cen­ter for Phar­ma­ceu­ti­cal Pol­i­cy and Pre­scrib­ing, not­ed in a Twit­ter thread Thurs­day night the con­trast be­tween the ques­tion and the “nar­row” fo­cus on the Phase III study.

FDA post­ed the vot­ing ques­tion for ad­com to­mor­row, but not sure how to in­ter­pret.

Do the safe­ty and ef­fi­ca­cy da­ta from the 300 per­son boost­er tri­al sup­port ap­proval? Sure, they 'sup­port it.' Are they suf­fi­cient for boost­er ap­proval for all 16+? No. https://t.co/1x6tNOIH3H pic.twit­ter.com/x1IC636bZj

— Walid Gel­lad, MD MPH (@walidgel­lad) Sep­tem­ber 17, 2021

— Max Gel­man

FDA ex­pands EUA for Eli Lil­ly’s an­ti­body cock­tail to cov­er pre­ven­tion

Eli Lil­ly and Ab­Cellera are square­ly back in ac­tion.

Just days af­ter the US re­sumed dis­tri­b­u­tion of their an­ti­body cock­tail na­tion­wide to fight against a surge in cas­es — dom­i­nat­ed by the Delta vari­ant — the com­pa­nies said the com­bo of bam­lanivimab and ete­se­vimab has been cleared for emer­gency use to pre­vent Covid-19 in peo­ple who have been ex­posed to some­one in­fect­ed with SARS-CoV-2 or at high risk of ex­po­sure, such as in the prison or nurs­ing home set­ting.

It marks the sec­ond EUA the FDA has is­sued for post-ex­po­sure pro­phy­lax­is, af­ter grant­i­ng the same ex­pan­sion for Re­gen­eron’s an­ti­bod­ies.

On top of pro­tect­ing peo­ple who have not been ful­ly vac­ci­nat­ed, Lil­ly notes that in­di­vid­u­als who can’t mount an ad­e­quate im­mune re­sponse to com­plete vac­ci­na­tion may ben­e­fit from the drugs. It’s sanc­tioned for high-risk in­di­vid­u­als 12 or old­er.

The com­bi­na­tion of a low vac­ci­na­tion rate and a rise in break­through Covid-19 cas­es has trans­lat­ed to sky­rock­et­ing de­mand for mon­o­clon­al an­ti­bod­ies. Just days ago, Re­gen­eron re­vealed the gov­ern­ment has placed a new, $2.9 bil­lion or­der for 1.4 mil­lion ad­di­tion­al dos­es of its an­ti­bod­ies.

Lil­ly had li­censed bam­lanivimab from Ab­Cellera and ete­se­vimab from Shang­hai’s Jun­shi to put to­geth­er the com­bo.

“The ex­pand­ed use au­tho­riza­tion for bam­lanivimab to­geth­er with ete­se­vimab pro­vides a way to pro­tect the sig­nif­i­cant num­ber of peo­ple who, be­cause of their sit­u­a­tion­al ex­po­sure risk or med­ical con­di­tion, re­main vul­ner­a­ble to COVID-19,” Ab­Cellera CEO Carl Hansen said in a state­ment. “More than 535,000 pa­tients have been treat­ed with bam­lanivimab alone or to­geth­er with ete­se­vimab, po­ten­tial­ly keep­ing more than 25,000 pa­tients out of the hos­pi­tal and sav­ing more than 10,000 lives.”

— Am­ber Tong

Re­searchers peg As­traZeneca/Ox­ford, Pfiz­er/BioN­Tech vac­cine im­mu­ni­ty about 1 year

A group of Ox­ford sci­en­tists says the Covid-19 vac­cine that their col­leagues have de­vel­oped with As­traZeneca ap­pears to kick up an­ti­bod­ies that last equal­ly as long as the ones elicit­ed by Pfiz­er and BioN­Tech’s ri­val shot.

An­a­lyz­ing an­ti-spike IGG an­ti­body re­spons­es among 186,527 vac­ci­nat­ed peo­ple in the UK to fig­ure out the du­ra­tion of pro­tec­tion of­fered by the two vac­cines, the re­searchers con­clud­ed:

Pro­tec­tion based on cur­rent pos­i­tiv­i­ty thresh­olds can last for at least 0.5-1 year for ChA­dOx1 and over a year for BNT162b2; how­ev­er, giv­en the re­duced ef­fec­tive­ness against vari­ants of con­cern, the du­ra­tion of pro­tec­tion may be sig­nif­i­cant­ly re­duced. These re­sults may in­form vac­ci­na­tion strate­gies; a third boost­ing dose may be need­ed, and could be pri­ori­tised to the more vul­ner­a­ble pop­u­la­tion groups.

They al­so found that no mat­ter when it’s giv­en af­ter the first dose, a sec­ond dose of ChA­dOx1 and BNT162b2 in­duced “sig­nif­i­cant boost­ing” of an­ti-spike an­ti­bod­ies tar­get­ing SARS-CoV-2.

There was, how­ev­er, a key dif­fer­ence: An­ti­body lev­els de­clined faster for younger in­di­vid­u­als af­ter a sec­ond dose of the Ox­ford/As­traZeneca vac­cine, while old­er peo­ple get­ting BNT162b2 saw their lev­els de­cline faster — al­though it was off­set by high­er peak lev­els.

“In the most vul­ner­a­ble groups, the net ef­fect was a sim­i­lar du­ra­tion of time above dif­fer­ent thresh­olds from the two vac­cines, but with longer du­ra­tions with BNT162b2 in younger groups,” they added.

No­tably, they al­so of­fered a coun­ter­point to re­cent stud­ies that sug­gest­ed longer dos­ing in­ter­vals may gen­er­ate more im­mu­ni­ty, sug­gest­ing that the dif­fer­ences in an­ti­body lev­els may be re­lat­ed to how and when those stud­ies mea­sured an­ti­body lev­els.

— Am­ber Tong

About five years ago, Amit Etkin had a breakthrough.

The Stanford neurologist, a soft-spoken demi-prodigy who became a professor while still a resident, had been obsessed for a decade with how to better define psychiatric disorders. Drugs for depression or bipolar disorder didn’t work for many patients with the conditions, and he suspected the reason was how traditional diagnoses didn’t actually get at the heart of what was going on in a patient’s brain.

While falling behind the biggest PD-(L)1 drugs in terms of sales, Roche has looked to carve out a space for its Tecentriq with a growing expertise in lung cancer. The drug will now take an early lead in the sought-after adjuvant setting — but competitors are on the way.

The FDA on Friday approved Tecentriq as an adjuvant therapy for patients with Stage II-IIIA non small cell lung cancer with PD-(L)1 scores greater than or equal to 1, making it the first drug of its kind approved in an early setting that covers around 40% of all NSCLC patients.

The FDA’s vaccine advisory committee on Thursday voted 19-0 in support of expanding Moderna’s Covid-19 vaccine EUA for booster doses for certain high-risk individuals. FDA is expected to authorize the Moderna booster shortly.

Similarly to the Pfizer booster shot, Moderna’s will likely be authorized for those older than 65, adults at high risk of severe Covid-19, and adults whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at high risk of serious complications of Covid-19. But unlike the Pfizer adcomm, where FDA had to scramble to get the committee to vote in favor of a booster, this committee was unanimous with the Moderna shot.