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.

An­oth­er ex­am­ple would be some­one who re­ceived the ini­tial two-dose se­ries of Pfiz­er or Mod­er­na, and who is el­i­gi­ble to get a boost­er (i.e., 65 years of age and old­er, 18 through 64 years of age at high-risk of se­vere Covid-19, and 18 through 64 years of age with fre­quent in­sti­tu­tion­al or oc­cu­pa­tion­al ex­po­sure to SARS-CoV-2) may re­ceive a shot of the Mod­er­na, Pfiz­er or a J&J vac­cine, at least six months af­ter com­plet­ing their pri­ma­ry vac­ci­na­tion.

“Fol­low­ing a pre­sen­ta­tion of clin­i­cal tri­al da­ta from the Na­tion­al In­sti­tute of Al­ler­gy and In­fec­tious Dis­eases, the Vac­cines and Re­lat­ed Bi­o­log­i­cal Prod­ucts Ad­vi­so­ry Com­mit­tee’s dis­cus­sion of in­for­ma­tion sub­mit­ted for con­sid­er­a­tion, along with the agency’s eval­u­a­tion of the avail­able da­ta, the FDA has de­ter­mined that the known and po­ten­tial ben­e­fits of the use of a sin­gle het­erol­o­gous boost­er dose out­weigh the known and po­ten­tial risks of their use in el­i­gi­ble pop­u­la­tions,” FDA said in a state­ment.

Kirsten Lyke

At that VRB­PAC meet­ing, ex­perts re­viewed da­ta from a mix-and-match study where par­tic­i­pants who re­ceived J&J’s sin­gle shot fol­lowed by a Mod­er­na shot saw a geo­met­ric mean fold rise (the ra­tio of post-vac­ci­na­tion titer val­ue to pre-vac­ci­na­tion titer val­ue) of 76-fold, ac­cord­ing to Kirsten Lyke of the Cen­ter for Vac­cine De­vel­op­ment and Glob­al Health at the Uni­ver­si­ty of Mary­land School of Med­i­cine. That com­pared to a 4.2 GM­FR in those who re­ceived two dos­es of J&J’s vac­cine, and a 35 GM­FR in those who got J&J’s vac­cine fol­lowed by the Pfiz­er/BioN­Tech vac­cine.

“What I would note is that the neu­tral­iz­ing an­ti­bod­ies did in­crease in re­sponse to any boost re­gard­less of the pri­ma­ry vac­ci­na­tion se­ries,” she said, al­so not­ing that the mR­NA vac­cines re­sult­ed in high­er an­ti­body titers in the first 28 days af­ter the boost.

Oth­er ex­perts called for the EUA for mix-and-match boost­ers so that they can be tracked, as the het­erol­o­gous sec­ond and third shots are oc­cur­ring in the re­al world with or with­out an FDA au­tho­riza­tion.

Ofer Levy, di­rec­tor of Boston Chil­dren’s Hos­pi­tal’s pre­ci­sion vac­cines pro­gram, ex­pressed con­cern over re­cent re­ports that some Amer­i­cans are tak­ing mat­ters in­to their own hands, re­ceiv­ing unau­tho­rized boost­ers and mix­ing prod­ucts.

“In the re­al world, all these kinds of com­bi­na­tions or ex­tra boost­ers are al­ready hap­pen­ing,” he said. “So I think it’s a mat­ter of some ur­gency for FDA to help sort out what is ad­mit­ted­ly a com­pli­cat­ed and chal­leng­ing sce­nario. But we can’t hide from it, and I do think we need to give guid­ance to the pub­lic.”

Sep­a­rate­ly, the agency al­so of­fered an EUA for a sin­gle boost­er half-dose of the Mod­er­na vac­cine that may be ad­min­is­tered at least 6 months af­ter com­ple­tion of the pri­ma­ry se­ries to se­niors, those at high risk of se­vere Covid, and those who work in places where there’s a high risk of ex­po­sure to the virus.

For J&J, FDA said the boost­er may be ad­min­is­tered for any adult, at least 2 months af­ter com­ple­tion of the sin­gle-dose pri­ma­ry reg­i­men.

Pe­ter Marks

Both of those rec­om­men­da­tions for Mod­er­na and J&J boost­ers fol­lowed unan­i­mous votes from the FDA’s vac­cine ad­comm.

The CDC’s Ad­vi­so­ry Com­mit­tee on Im­mu­niza­tion Prac­tices will vote on a rec­om­men­da­tion to­day for which groups should re­ceive boost­ers. It will al­so dis­cuss new safe­ty up­dates. But as the Pfiz­er boost­er au­tho­riza­tion showed, the CDC di­rec­tor does not have to fol­low ACIP’s rec­om­men­da­tions.

“We will work to ac­crue ad­di­tion­al da­ta as quick­ly as pos­si­ble to fur­ther as­sess the ben­e­fits and risks of the use of boost­er dos­es in ad­di­tion­al pop­u­la­tions and plan to up­date the health­care com­mu­ni­ty and pub­lic with our de­ter­mi­na­tion in the com­ing weeks,” CBER di­rec­tor Pe­ter Marks said in a state­ment.

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

Moderna CEO Stéphane Bancel faced a barrage of questions from the Senate health committee on Wednesday but emerged mostly unscathed as he defended the quadrupling of the price of the company’s blockbuster Covid-19 vaccine in the US, from about $26 per dose to $130 per dose.

What’s behind that rise in price, many senators on both sides of the aisle questioned, and Bancel offered a variety of reasons. First and foremost, the company is expecting a 90% reduction in demand for its vaccine next fall, when the FDA is likely to roll out another booster campaign to fight Covid-19.

Incyte touted an accelerated approval for its PD-1 retifanlimab in a rare skin cancer on Wednesday, roughly a year and a half after the drug suffered a rejection in squamous cell carcinoma of the anal canal (SCAC).

Retifanlimab, marketed as Zynyz, was approved for metastatic or recurrent locally advanced Merkel cell carcinoma (MCC), a fast-growing skin cancer typically characterized by a single, painless nodule. It’s roughly 40 times rarer than melanoma, according to the nonprofit Skin Cancer Foundation — but incidence is growing, particularly among older adults, Incyte said in its announcement.

Novartis is calling off a UK-based trial for Leqvio in the primary prevention of cardiovascular events in patients with high cholesterol, the company confirmed on Wednesday.

The Swiss pharma giant made the decision after “careful evaluation,” a spokesperson told Endpoints News via email. The trial, dubbed ORION-17, was planned in partnership with England’s National Health Service (NHS) and was part of the company’s strategy to establish Leqvio as a standard of care in cardiovascular disease management.