Pascal Soriot, AstraZeneca CEO (Raphael Lafargue/Abaca/Sipa USA; Sipa via AP Images)

Up­dat­ed: Study shows As­traZeneca's Covid-19 mAb Evusheld may not work against dom­i­nant Omi­cron strain

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.

Jean-Paul Clozel, Idorsia CEO (Patrick Straub/Keystone via AP Images)

Idor­si­a's brain bleed drug flunks PhI­II tri­al, a decade af­ter pre­vi­ous flop

Idorsia’s long journey with clazosentan came to an abrupt “unexpected result” Monday morning with a Phase III flop.

The Swiss biopharma said the drug did not meet the main goal of the late-stage REACT study, conducted in the US, Canada and Europe since early 2019.

The 409-patient trial tested the intravenous drug’s ability to prevent complications due to delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage (aSAH), in which blood vessels in the brain narrow and blood accumulates around the brain’s surface, which then dials up the pressure on the brain.

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Kenji Yasukawa, Astellas CEO (Photographer: Akio Kon/Bloomberg via Getty Images)

Astel­las taps chief strat­e­gy of­fi­cer as next CEO to 'go on the ag­gres­sive'

Five years into its big R&D revamp, Astellas says it’s time for a changing of the guard.

Kenji Yasukawa, who took over as president and CEO in 2018, will step down to become chairman of the board in April, making room for Naoki Okamura to take over. Okamura joined the company in 1986 and has served in a variety of finance, business and strategy roles, including most recently as chief strategy officer.

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Clin­i­cal tri­al di­ver­si­ty da­ta show mis­match be­tween en­roll­ment and dis­ease preva­lence, GSK says

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.

The Big Phar­ma dis­card pile; Lay­offs all around while some biotechs bid farewell; New Roche CEO as­sem­bles top team; 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.

With earnings seasons in full swing, we’ve listened in on all the calls so you don’t have to. But news is popping up from all corners, so make sure you check out our other updates, too.

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Photo: Julia Weeks/AP Images

FDA ax­es re­quire­ment for pos­i­tive Covid test be­fore Paxlovid use

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.”

Sen. Ron Wyden (D-OR) (Francis Chung/E&E News/Politico via AP Images)

In­fla­tion re­bates in­com­ing: Wyden calls on CMS to move quick­ly as No­var­tis CEO pledges re­ver­sal

Senate Finance Chair Ron Wyden (D-OR) this week sent a letter to the head of the Centers for Medicare & Medicaid Services seeking an update on how and when new inflation-linked rebates will take effect for drugs that see major price spikes.

The newly signed Inflation Reduction Act requires manufacturers to pay a rebate to Medicare when they increase drug prices faster than the rate of inflation.

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Trodelvy notch­es a win in most com­mon form of breast can­cer

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.

Raymond Stevens, Structure Therapeutics CEO

Be­hind Fri­day's $161M IPO: A star sci­en­tist, GPCR drug dis­cov­ery and a plan to chal­lenge phar­ma in di­a­betes

What does it take to pull off a $161 million biotech IPO these days?

In Structure Therapeutics’ case, it means having a star scientist co-founder paired with the computational drug discovery company Schrödinger, $198 million in private funding from blue-chip investors, almost six years of research work on G protein-coupled receptors and a slate of oral, small-molecule drugs, with an eye on the huge and growing diabetes and weight-loss market.

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Af­ter 13 years, Ramy Mah­moud steps in­to CEO seat at Opti­nose; Ru­pert Vessey set to ex­it Bris­tol My­ers in Ju­ly

After 13 years as president and COO at Optinose, Ramy Mahmoud has stepped into a new role as its CEO. He is taking the place of Peter Miller, who stepped down earlier this week, though Miller is still staying with the company as a consultant.

In 2010, the two business partners joined Optinose to take it in a new direction, transforming it from a delivery platform to product company. They previously worked together at Johnson & Johnson, when Miller was president at Janssen and Mahmoud headed medical affairs. Miller said after he learned about Optinose, “I did what I always do, which is find people smarter than me to talk with about the idea. And the first person I called was Ramy … and I said, ‘Hey, Ramy, what do you think of this technology?’”

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