As­traZeneca’s pro­phy­lac­tic treat­ment for Covid-19, known as Evusheld, has sur­vived where oth­er mAbs failed, show­ing ef­fi­ca­cy for the im­muno­com­pro­mised and oth­ers who can­not be vac­ci­nat­ed across mul­ti­ple vari­ants, in­clud­ing Delta and sev­er­al Omi­cron sub­vari­ants.

But new cor­re­spon­dence pub­lished in the New Eng­land Jour­nal of Med­i­cine yes­ter­day says that the dom­i­nant Omi­cron sub­vari­ants right now are much less sus­cep­ti­ble to Evusheld, which is a com­bi­na­tion of tix­agevimab and cil­gav­imab. That da­ta may end up re­sult­ing in a pause in the use of Evusheld, al­though an As­traZeneca spokesper­son in­sists that it won’t, and HHS has not in­di­cat­ed that there’ll be a pause any­time soon.

An As­traZeneca spokesper­son told End­points via email that “stud­ies have shown that Evusheld neu­tral­izes all known vari­ants of con­cern, in­clud­ing BA.4/5,” adding:

• The pub­li­ca­tion da­ta do not sup­port that Evusheld does not work against BA.5, and the NE­JM au­thors do not make that con­clu­sion. The NE­JM da­ta show the com­bi­na­tion of the two an­ti­bod­ies that com­prise Evusheld neu­tral­izes BA.5, with a FRNT50 (a lev­el of an an­ti­body’s neu­tral­iz­ing po­ten­cy, al­so called IC50) of 192ng/ml.  The lim­it of de­tec­tion of the as­say was 10,000ng/ml.
• In the NE­JM study, the FRNT50 for Evusheld against BA.1 is 351. There­fore, it makes sense that Evusheld would re­main ef­fec­tive against BA.5, since the FRNT50 against BA.5 is low­er than for BA.1 (192 for BA.5 and 361 for BA.1; low­er means high­er po­ten­cy)
• Evusheld start­ed with high­ly po­tent in vit­ro neu­tral­iza­tion against the orig­i­nal SARS-CoV-2 virus and ear­li­er vari­ants. There­fore, IC50/FRNT50 lev­el dif­fer­ences and fold changes may be re­port­ed against cer­tain Omi­cron vari­ants even though ac­tiv­i­ty is re­tained and above the thresh­old need­ed to neu­tral­ize the vari­ant.
• There have been no dis­cus­sions with the US FDA over a pause of use of Evusheld.
• The FDA has re­viewed pre­vi­ous neu­tral­iza­tion da­ta against BA.4/.5 that are now in­clud­ed in the re­vised Evusheld Fact Sheet. That da­ta are gen­er­al­ly in line with the new da­ta re­port­ed in the NE­JM.

The U.S gov­ern­ment has spent more than $1.5 bil­lion in de­vel­op­ing and ac­quir­ing dos­es of Evusheld dur­ing the pan­dem­ic, and As­traZeneca re­port­ed $469 mil­lion in world­wide sales of the mAb com­bo in Q1 of this year.

The re­searchers from Japan, the Uni­ver­si­ty of Wis­con­sin-Madi­son, Johns Hop­kins and Ic­ahn School of Med­i­cine at Mount Sinai wrote that Eli Lil­ly’s bebtelovimab may be the on­ly mAb left stand­ing that’s ef­fec­tive against three dif­fer­ent Omi­cron sub­lin­eages – BA.2.12.1, BA.4, and BA.5.

Re­gen­eron’s com­bo of casiriv­imab and imde­vimab, as well as GSK’s sotro­vimab, both of which have been pulled from the US mar­ket in re­cent months, al­so may not pro­vide ef­fec­tive treat­ment against BA.2.12.1, BA.4, or BA.5, the study shows. Lil­ly’s oth­er mAb com­bo of bam­lanivimab and ete­se­vimab al­so was pulled from the mar­ket pre­vi­ous­ly.

“Our find­ings show that the se­lec­tion of mon­o­clon­al an­ti­bod­ies to treat pa­tients who are in­fect­ed with omi­cron vari­ants should be care­ful­ly con­sid­ered,” the au­thors wrote.

The FDA late last month au­tho­rized re­vi­sions to Evusheld’s dos­ing, say­ing that, “Non­clin­i­cal da­ta and phar­ma­co­ki­net­ic mod­el­ing sug­gest that ac­tiv­i­ty against these sub­vari­ants [BA.2, BA.2.12.1, BA.4, and BA.5] may be re­tained for six months at drug con­cen­tra­tions achieved fol­low­ing an Evusheld dose of 300 mg of tix­agevimab and 300 mg cil­gav­imab.”

And the agency now rec­om­mends re­peat dos­ing every six months. But sup­plies of the pro­phy­lac­tic mAb are not run­ning thin in the US, with HHS re­port­ing that a lit­tle less than half of about 800,000 cours­es of Evusheld have been ad­min­is­tered so far.

How­ev­er, the good news, de­spite some lim­i­ta­tions to the re­search, is that the au­thors found three small-mol­e­cule an­tivi­ral drugs against Covid-19 — Gilead’s remde­sivir, Mer­ck’s mol­nupi­ravir, and Pfiz­er’s nir­ma­trelvir — all still work against the lat­est Omi­cron sub­lin­eages.

“The main lim­i­ta­tion of our study is the lack of clin­i­cal da­ta on the ef­fi­ca­cy of these mon­o­clon­al an­ti­bod­ies and an­tivi­ral drugs for the treat­ment of pa­tients in­fect­ed with BA.2.12.1, BA.4, or BA.5 sub­vari­ants,” the re­searchers added.

Ed­i­tor’s note: Ar­ti­cle up­dat­ed with com­ment from As­traZeneca.

A lack of diversity in clinical trials has persisted despite decades of initiatives to try to turn the tide.

In a recent review of 17 years of clinical trials, drugmaker GSK found that there were some mismatches between the demographics of its US-based trials and how prevalent diseases were in those populations.

The results, the company says, will help GSK and others design studies that better represent epidemiological rates within races and ethnicities.

FDA announced today that doctors and pharmacists can now prescribe Paxlovid to patients without a positive test for Covid-19.

CDER Director Patrizia Cavazzoni reissued Paxlovid’s authorization letter Wednesday, saying it has revised the authorization to “no longer require positive results of direct SARS-CoV-2 viral testing.” The EUA now requires instead that adults and kids 12 years of age and older have a “current diagnosis of mild-to-moderate COVID-19.”

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.