Covid-19 roundup: FDA re­veals boost­er ad­comm ques­tion; Eli Lil­ly's an­ti­body cock­tail cleared for pre­ven­tion

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.

— 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

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

So — that pig-to-hu­man trans­plant; Po­ten­tial di­a­betes cure reach­es pa­tient; Ac­cused MIT sci­en­tist lash­es back; 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.

We’re incredibly excited to welcome Beth Bulik, seasoned pharma marketing reporter, to the team. You can find much of her work in our new Marketing channel — and in her weekly newsletter, Endpoints PharmaRx, which will launch in early November. Add it to your subscriptions here.

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NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

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How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data are messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data are exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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David Livingston (Credit: Michael Sazel for CeMM)

Renowned Dana-Far­ber sci­en­tist, men­tor and bio­phar­ma ad­vi­sor David Liv­ingston has died

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.

Pfiz­er pitch­es its Covid-19 vac­cine for younger chil­dren ahead of ad­comm next week

Pfizer will present its case to the FDA’s vaccine adcomm next week, seeking authorization for a lower-dose version of its Covid-19 vaccine for kids ages 5 through 12, which the Biden administration said will likely begin rolling out early next month.

Two primary doses of the 10 µg vaccine (the dose for those ages 12 and up is 30 μg) given 3 weeks apart in this group of children “have shown a favorable safety and tolerability profile, robust immune responses against all variants of concern including Delta, and vaccine efficacy of 90.7% against laboratory-confirmed symptomatic COVID-19,” the company said in briefing documents ahead of next Tuesday’s meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee.

No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty

 

I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

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Boost­er bo­nan­za: FDA en­dors­es 'mix-and-match' scheme, and Mod­er­na and J&J too

The FDA late Wednesday signed off on authorizing the use of heterologous — or what FDA calls a “mix and match” of a primary vaccine series and different booster doses — for all currently available Covid-19 vaccines, in addition to separately authorizing Moderna and J&J boosters.

On the mix-and-match approach, which FDA officials insisted isn’t too confusing in a press conference, the agency offered the example of an 18-year-old who received the J&J shot at least two months ago and may now receive a single booster of the J&J, a half dose of the Moderna, or the Pfizer-BioNTech booster.