Blake Ferguson, 12, receives his first dose of the Pfizer vaccine (Photo by Anthony Behar/Sipa USA)(Sipa via AP Images)

Covid-19 vac­cines for kids: FDA spells out ques­tions on im­muno­bridg­ing, safe­ty fol­lowup ahead of ad­comm

NI­AID chief An­tho­ny Fau­ci pre­dict­ed days ago that Covid-19 vac­cines for younger chil­dren will be avail­able by the end of the year or ear­ly next year. But what re­quire­ments should they sat­is­fy be­fore get­ting the clear­ance from the FDA? The agency laid out some of its thoughts on brief­ing doc­u­ments for an ad­vi­so­ry com­mit­tee set for Thurs­day.

As with the first ex­pert pan­els con­vened to dis­cuss Covid-19 vac­cine reg­u­la­tions, the ad­comm won’t be talk­ing about spe­cif­ic prod­ucts. Rather, the goal is to gauge their opin­ion on frame­work, such as da­ta need­ed and ap­pro­pri­ate end­points.

Right now, Pfiz­er and BioN­Tech have the on­ly shot that’s au­tho­rized for ado­les­cents above the age of 12 — but noth­ing is sanc­tioned yet for those younger. (Cana­da and the EU, though, have green­light­ed Mod­er­na’s jab for the same pop­u­la­tion.)

Reg­u­la­tors set the stage by not­ing that al­though pe­di­atric pop­u­la­tions seem less like­ly to be in­fect­ed by the coro­n­avirus (and when they do, tend not to get as sick), many have still been hos­pi­tal­ized or died from Covid-19:

As of May 25, 2021, ap­prox­i­mate­ly 553,000 and 2.7 mil­lion COVID-19 cas­es, re­spec­tive­ly, were re­port­ed in chil­dren 0-4 and 5-17 years of age in the US, among which 121 (0.02%) and 278 (0.01%), re­spec­tive­ly, were fa­tal, and more than 38,000 of which re­sult­ed in hos­pi­tal­iza­tions re­port­ed since Au­gust 1, 2020, in pa­tients 0-17 years of age

The FDA em­pha­sized that any au­tho­riza­tion for pe­di­atric use should fol­low “sub­stan­tial ev­i­dence of ef­fec­tive­ness from ad­e­quate and well-con­trolled tri­als” plus am­ple safe­ty da­ta. Yet with three vac­cines from Pfiz­er/BioN­Tech, Mod­er­na and J&J al­ready show­ing ef­fi­ca­cy in adults, they won­der if the ev­i­dence could take a dif­fer­ent shape.

Giv­en the low­er in­fec­tion, hos­pi­tal­iza­tion and death rates in chil­dren, af­ter all, the dy­nam­ics are quite dif­fer­ent.

FDA ac­knowl­edges that di­rect demon­stra­tion of ef­fec­tive­ness in field ef­fi­ca­cy tri­als may not be fea­si­ble in pe­di­atric pop­u­la­tions and thus, fol­low­ing di­rect demon­stra­tion of pro­tec­tion in adults, ef­fec­tive­ness of the same vac­cine could be in­ferred in pe­di­atric pop­u­la­tions by im­muno­bridg­ing. … In this ap­proach, an im­mune re­sponse bio­mark­er(s) elicit­ed by the vac­cine in a pe­di­atric age group is com­pared to the same im­mune re­sponse bio­mark­er(s) elicit­ed by the same vac­cine in a rel­e­vant adult age group, with for­mal sta­tis­ti­cal hy­poth­e­sis test­ing to demon­strate that the mea­sured im­mune re­sponse in the pe­di­atric age group is non-in­fe­ri­or to that in adults.

There are al­so ques­tions about whether there should be a longer safe­ty fol­lowup than the two months man­dat­ed for the adult and ado­les­cent OKs.

One oth­er spe­cif­ic con­sid­er­a­tion for chil­dren, the FDA added, would be how the Covid-19 vac­cine might in­ter­fere with oth­er rou­tine­ly rec­om­mend­ed im­mu­niza­tions. Vac­cine mak­ers are en­cour­aged to in­clude in­for­ma­tion but will not be re­quired to as­sess con­comi­tant ad­min­is­tra­tion to sup­port li­cen­sure.

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

All about Omi­cron; We need more Covid an­tivi­rals; GSK snags Pfiz­er’s vac­cine ex­ec; Janet Wood­cock’s fu­ture at FDA; and more

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Merck's new antiviral molnupiravir (Quality Stock Arts / Shutterstock)

As Omi­cron spread looms, oral an­tivi­rals ap­pear to be one of the best de­fens­es — now we just need more

After South African scientists reported a new Covid-19 variant — dubbed Omicron by the WHO — scientists became concerned about how effective vaccines and monoclonal antibodies might be against it, which has more than 30 mutations in the spike protein.

“I think it is super worrisome,” Dartmouth professor and Adagio co-founder and CEO Tillman Gerngross told Endpoints News this weekend. Moderna CEO Stéphane Bancel echoed similar concerns, telling the Financial Times that experts warned him, “This is not going to be good.”

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Pfiz­er, Am­gen and Janssen seek fur­ther clar­i­ty on FDA's new ben­e­fit-risk guid­ance

Three top biopharma companies are seeking more details from the FDA on how the agency conducts its benefit-risk assessments for new drugs and biologics.

While Pfizer, Amgen and Janssen praised the agency for further spelling out its thinking on the subject in a new draft guidance, including a discussion of patient experience data as part of the assessment, the companies said the FDA could’ve included more specifics in the 20-page draft document.

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Re­searchers move clos­er to de­ci­pher­ing blood clots from As­traZeneca, J&J's Covid-19 vac­cines

Researchers may be nearing an answer for the mysterious and life-threatening blood clots that appeared on very rare occasions in people who received the J&J or AstraZeneca Covid-19 vaccine.

The new work builds on an early hypothesis researchers in Norway put forward last spring, when the cases first cropped up. They proposed the events were similar to blood clots that can occur in a small subset of patients who receive heparin, one of the most commonly used blood thinners.

Janet Woodcock (AP Images)

Janet Wood­cock plots her fu­ture at FDA, with se­nior ad­vi­sor role to fall back on if Califf wins con­fir­ma­tion

Acting FDA commissioner Janet Woodcock has been the face of just about every drug approval decision at the agency since the turn of the century. Since the pandemic began, she’s moved between the top of the drugs center to the head of therapeutics at Operation Warp Speed, leading the drive for work on Covid-targeted mAbs and antivirals.

Looking forward — and pending a quick Senate confirmation to cement Rob Califf’s return to the top of FDA early next year — Woodcock’s role at the agency will again be in flux.

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Richard Pazdur (via AACR)

Ac­cel­er­at­ed ap­proval re­forms need mean­ing­ful con­fir­ma­to­ry tri­al im­prove­ments, pro­fes­sors write in Sci­ence

Outside of Covid-19, 2021 has been the year of the accelerated approval.

Beginning last spring, FDA openly challenged six “dangling” accelerated approvals (hadn’t confirmed their clinical benefit yet), three of which were later pulled by the companies.

Then in June, FDA pulled out the accelerated approval pathway, seemingly out of nowhere, to sign off on Biogen’s controversial Alzheimer’s drug Aduhelm. It hadn’t even been mentioned at the drug’s adcomm.

Lisa Deschamps, AviadoBio CEO

Ex-No­var­tis busi­ness head hops over to a gene ther­a­py start­up — and she's reeled in $80M for a dash to the clin­ic

Neurologist and King’s College London professor Christopher Shaw has been researching neurodegenerative diseases like ALS and collaborating with drugmakers for the last 25 years in the hopes of pushing new therapies forward. But unfortunately, none of those efforts have come anywhere close to fruition.

“So, you know, after 20 years in the game, I said, ‘Let’s try and do it ourselves,’” he told Endpoints News. 

In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.