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.

UP­DAT­ED: In a fresh dis­ap­point­ment, Am­gen spot­lights a ma­jor safe­ty is­sue with KRAS com­bo

Amgen had hoped that its latest study matching its landmark KRAS G12C drug Lumakras with checkpoint inhibitors would open up its treatment horizons and expand its commercial potential. Instead, the combo spurred safety issues that blunted efficacy and forced the pharma giant to alter course on its treatment strategy, once again disappointing analysts who have been tracking the drug’s faltering sales and limited therapeutic reach.

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Ad­dress­ing the ‘Ca­pac­i­ty Crunch’ with a Scal­able Plat­form Process Ap­proach

The field of gene therapy has been diligently moving forward over the past several decades to bring potentially life-saving treatments to patients with genetic diseases. In addition to two approved adeno-associated viral (AAV) gene therapies, there are more than 250 AAV gene therapies in various clinical trial stages.1 AAV vectors remain the most frequently used vector for delivering therapeutic transgenes to target tissues due to their demonstrated and lasting clinical efficacy and extensive safety track record. As AAV therapies advance through clinical trials and into commercialization, many biotech companies are turning to contract development and manufacturing organizations (CDMOs) to prepare their programs for late-stage clinical and commercial scale manufacturing. Given the scope and scale of the manufacturing needs that will accompany regulatory approvals for these assets, CDMOs continue to expand their capacity to meet the needs of increasing prevalent patient populations. However, despite rapid growth, projected gene therapy manufacturing demands still outpace the collective capacity of the CDMO industry.

A $5B Pfiz­er buy­out? Am­gen, Gilead head­line M&A Thurs­day; Al­ny­lam's AT­TR sweep; An­drew Lo's rare dis­ease quest; 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.

One of the cool things about adding EndpointsPharma to the daily roster is that my colleagues can now dedicate time to tracking quarterly updates and tuning into calls with Big Pharma companies. Check out their dispatch from the Q2 earnings below.

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Albert Bourla, Pfizer CEO (Laurent Gillieron/Keystone via AP)

Break­ing: Pfiz­er in hot pur­suit of a $5B buy­out of Glob­al Blood Ther­a­peu­tics — re­port

Pfizer CEO Albert Bourla has vowed to leave no stone unturned in the search for new biotech deals, and the BD team is not letting him down.

The Wall Street Journal reported today that Pfizer is in the final stages of acquiring Global Blood Therapeutics for $5 billion. According to the Journal report, though, Pfizer is not the only buyer at the deal table and while the pharma giant may be close to clinching it, there are no guarantees it will continue.

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Bob Bradway, Amgen CEO (Justin Kase Conder/AP Images for Amgen)

UP­DAT­ED: Am­gen chief Brad­way nabs a rare dis­ease play­er in $4B buy­out as the M&A tem­po ac­cel­er­ates

Amgen CEO Bob Bradway is bellying up to the M&A table today, scooping up the newly anointed commercial biotech ChemoCentryx $CCXI and its recently approved rare disease drug for $3.7 billion out of the cash stockpile. The deal comes in at $52 a share — a hefty increase over the $24.11 close yesterday.

Bradway and the Amgen team get a drug called Tavneos (avacopan) in the deal, a complement factor C5a inhibitor OK’d to treat anti-neutrophil cytoplasmic autoantibody (ANCA)-vasculitis, an autoimmune disease which can be lethal.

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George Yancopoulos, Regeneron president and CSO (Brendan McDermid/Reuters/Alamy)

George Yan­copou­los says he's on the trail of the holy grail: ‘This could rep­re­sent the next break­through for im­munother­a­py’

Two of the most outspoken — and successful — drug developers in biotech say they’ve collected early-stage clinical data that are pointing them down the trail to the holy grail in cancer immunotherapy R&D.

While analysts largely busied themselves today with chronicling the ongoing success of Regeneron’s two big cash cows — Dupixent and Eylea — chief scientist George Yancopoulos and CEO Len Schleifer used the Q2 call to spotlight their early success with a combination of the “homegrown” PSMAxCD28 costimulatory bispecific antibody REGN5678 in combination with their PD-1 checkpoint Libtayo. The presentation comes just weeks after Regeneron completed a deal to gather all rights to the PD-1 that had been in Sanofi’s hands. And the two top execs are unstinting in their praise of the potential of a whole set of costimulatory pipeline projects which they say may finally deliver the long-awaited next-level approach to broadening the immunotherapy field of drugs.

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(AP Photo/Richard Vogel, File)

US de­clares mon­key­pox a na­tion­al health emer­gency, as new drug­mak­ers con­sid­er en­ter­ing vac­cine race

Rising monkeypox cases have put the US on high alert as it announces a national health emergency, which grants the government more power in its response.

The news comes as Bavarian Nordic continues to fill orders for its Jynneos vaccine and other companies – including Moderna – consider jumping into the vaccine race. Meanwhile, the New York Times reports that the US has allowed around 20 million doses of smallpox vaccine in its stockpile to expire.

Vlad Coric, Biohaven CEO

Bio­haven touts surge in Nurtec sales ahead of Pfiz­er takeover

Forget buyer’s remorse, Pfizer is likely feeling pretty good about its $11.6 billion Biohaven takeover deal following reports of a 57% sales boost for migraine med Nurtec.

Biohaven reported in Q2 results on Friday that it’s cleared the necessary antitrust hurdles to move forward with the sale of its calcitonin gene-related peptide (CGRP) assets to Pfizer. However, because the company is “focused on workstreams related to the closing” of the deal, it did not host a call with analysts and investors.

Pharma ads are showing up on cooler screens at retail pharmacies, including Walgreens and CVS, under a new OptimizeRx deal (OptimizeRx)

Phar­ma brands chill in the phar­ma­cy re­tail aisle with new style ads on re­frig­er­a­tion screens

Want a prescription drug with that soda? While not directly possible, ads for pharma brands now running on beverage and snack cooler screens at pharmacy retailers may at least inspire customers to think about it.

OptimizeRx is hooking up with Cooler Screens media company to bring prescription drug advertising to refrigerator front doors at pharmacies including Walgreens, CVS and Kroger.

The “point of dispense” ads show a full-door image on the cooler doors when a shopper is 12 feet away, but shrinks down to a smaller banner-sized ad so that the refrigerator contents can be seen when a person gets closer. The doors — which have to be specially installed by Cooler Screens — can detect when a person is nearby, how long a person “dwells” in front of the ad and if they do or don’t open the door.

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