Stéphane Bancel, Moderna CEO (Steven Ferdman/Getty Images)

Covid-19 roundup: Mod­er­na vac­cine kicks up an­ti­bod­ies against Delta vari­ant; UK study val­i­dates mix-and-match ap­proach for Pfiz­er-As­traZeneca

In an con­tin­ued ef­fort to mon­i­tor the ef­fec­tive­ness of its Covid-19 vac­cine, Mod­er­na has rolled out the lat­est slate of neu­tral­iza­tion da­ta against dif­fer­ent vari­ants — in­clud­ing the Delta vari­ant first iden­ti­fied in In­dia.

The da­ta were pub­lished on the preprint serv­er bioRx­iv as the Delta vari­ant has en­gulfed a num­ber of coun­tries, lead­ing to resur­gence of in­fec­tions.

De­ploy­ing a well-doc­u­ment­ed method, in­ves­ti­ga­tors took blood sam­ples from eight par­tic­i­pants of Mod­er­na’s Phase I tri­al one week af­ter their sec­ond dose of mR­NA-1273, and pit­ted them against pseudovirus en­gi­neered to bear fea­tures of vari­ants of con­cerns (VOCs), in­clud­ing the “the Be­ta vari­ant (B.1.351, first iden­ti­fied in South Africa), three lin­eage vari­ants of B.1.617 (first iden­ti­fied in In­dia), in­clud­ing the Kap­pa (B.1.617.1) and the Delta vari­ants (B.1.617.2); the Eta vari­ant (B.1.525, first iden­ti­fied in Nige­ria); and the A.23.1 and A.VOI.V2 vari­ants first iden­ti­fied in Ugan­da and An­go­la, re­spec­tive­ly.”

They then com­pared the neu­tral­iz­ing an­ti­body lev­els to that of the wild type virus first dis­cov­ered in Wuhan.

They re­port­ed:

Among VOCs test­ed, serum-elicit­ed neu­tral­iza­tion of the B.1.1.7 (Al­pha) vari­ant was com­pa­ra­ble to D614G; a range of re­duced neu­tral­iza­tion titers com­pared to D614G were ob­served for oth­er VOCs in­clud­ing the B.1.351 (Be­ta), B.1.617.2 (Delta), and P.1 (Gam­ma) vari­ants, with re­duc­tions rang­ing from 2.1-fold to 8.4-fold.

To Mod­er­na CEO Stéphane Ban­cel, the da­ta are “en­cour­ag­ing” in that they sup­port his vac­cine’s sta­tus as an ef­fec­tive “pri­ma­ry se­ries vac­cine” even against new­ly de­tect­ed vari­ants.

The biotech is al­so study­ing a mul­ti­va­lent boost­er can­di­date, which they’re call­ing mR­NA-1273.211, con­tain­ing both the orig­i­nal vac­cine and a new jab de­signed to tar­get the Be­ta vari­ant. — Am­ber Tong

UK study val­i­dates mix-and-match ap­proach for Pfiz­er-As­traZeneca

Some of the first da­ta for a mix-and-match vac­cine reg­i­men are in, and they’re en­cour­ag­ing for the UK and much of Eu­rope.

The Ox­ford study, called Com-COV, found that ad­min­is­ter­ing a shot of Pfiz­er/BioN­Tech vac­cine as a sec­ond dose af­ter the As­traZeneca vac­cine pro­duced stronger im­mune re­spons­es than giv­ing two shots of the As­traZeneca vac­cine.

The re­sults, which fo­cused on dos­ing at four-week in­ter­vals, are per­haps un­sur­pris­ing giv­en that Pfiz­er’s vac­cine has ap­peared more ef­fec­tive across the board than the As­traZeneca jab. But, giv­en the per­snick­ety, un­pre­dictable na­ture of the im­mune sys­tem, they were not as­sured.

The re­sults pro­vide the first good da­ta to sup­port what the UK and broad swaths of Eu­rope are al­ready do­ing: Amid short­ages of As­traZeneca dos­es and con­cerns about its con­nec­tion to rare but se­ri­ous blood clots, those na­tions al­lowed or en­cour­aged peo­ple who re­ceived a shot of their jab to use an mR­NA shot for their sec­ond dose.

The study in­di­cat­ed, though, that not all com­bi­na­tions were cre­at­ed equal. A shot of As­traZeneca then a shot of Pfiz­er pro­duced a bet­ter an­ti­body re­sponse, but a shot of Pfiz­er then As­traZeneca pro­duced a high­er T cell re­sponse.

The same study is now ex­am­in­ing the re­sults of giv­ing the vac­cines 12 weeks apart. That sched­ule aligns with how the vac­cines have been rolled out in the UK and some da­ta sug­gest the As­traZeneca vac­cine works bet­ter when giv­en at longer in­ter­vals. — Ja­son Mast

Lead­ing Chi­nese vac­cine proves safe in chil­dren

One of the lead­ing Chi­nese-made vac­cines ap­pears to be safe and to in­duce an­ti­bod­ies in chil­dren, po­ten­tial­ly adding an­oth­er tool, along­side the Pfiz­er and Mod­er­na shots, to pro­tect those un­der the age of 18.

Sino­vac pub­lished da­ta in The Lancet Mon­day show­ing that its in­ac­ti­vat­ed virus vac­cine elicit­ed an­ti­bod­ies in 96% of 550 chil­dren and ado­les­cents in Chi­na. Mild or mod­er­ate ad­verse events were rel­a­tive­ly un­com­mon com­pared to oth­er vac­cines, with 26% of vol­un­teers re­port­ing one such event, and there was on­ly one se­ri­ous ad­verse event — a case of pneu­mo­nia.

Al­though Sino­vac is one of the least ef­fi­ca­cious Covid-19 vac­cines au­tho­rized in any coun­try, with Phase III da­ta show­ing around 51% pro­tec­tion against symp­to­matic dis­ease, it still ap­peared large­ly pro­tec­tive against hos­pi­tal­iza­tion or death and has be­come a key pil­lar of vac­ci­na­tion cam­paigns in coun­tries across Asia.  The com­pa­ny claims to have de­liv­ered more than 600 mil­lion dos­es as of June 1. — Ja­son Mast

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

What Will it Take to Re­al­ize the Promise and Po­ten­tial of Im­mune Cell Ther­a­pies?

What does it take to get to the finish line with a new cancer therapy – fast? With approvals in place and hundreds of immune cell therapy candidates in the pipeline, the global industry is poised to create a fundamental shift in cancer treatments towards precision medicine. At the same time, unique challenges associated with cell and process complexity present manufacturing bottlenecks that delay speed to market and heighten cost of goods sold (COGS) — these hurdles must be overcome to make precision treatments an option for every cancer patient. This series of articles highlights some of the key manufacturing challenges associated with the production of cell-based cancer therapies as well as the solutions needed to transcend them. Automation, process knowledge, scalability, and assured supply of high-quality starting material and reagents are all critical to realizing the full potential of CAR-based therapies and sustaining the momentum achieved in recent years. The articles will highlight leading-edge technologies that incorporate these features to integrate across workflows, accelerate timelines and reduce COGS – along with how these approaches are enabling the biopharmaceutical industry to cross the finish line faster with new treatment options for patients in need.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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Lat­est news: It’s a no on uni­ver­sal boost­ers; Pa­tient death stuns gene ther­a­py field; In­side Tril­li­um’s $2.3B turn­around; 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.

Next week is shaping up to be a busy one, as our editor-in-chief John Carroll and managing editor Kyle Blankenship lead back-to-back discussions with a great group of experts to discuss the weekend news and trends. John will be spending 30 minutes with Jake Van Naarden, the CEO of Lilly Oncology, and Kyle has a brilliant panel lined up: Harvard’s Cigall Kadoch, Susan Galbraith, the new head of cancer R&D at AstraZeneca, Roy Baynes at Merck, and James Christensen at Mirati. Don’t miss out on the action — sign up here.

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President Biden and Pfizer CEO Albert Bourla (Patrick Semansky/AP Images)

Chaot­ic ad­comm sees Pfiz­er/BioN­Tech boost­ers re­ject­ed for gen­er­al pop­u­la­tion, but rec­om­mend­ed for old­er and high-risk pop­u­la­tions

With just days before President Joe Biden’s Covid-19 booster rollout is set to go into effect, an FDA advisory committee appeared on the verge of not recommending boosters for anyone in the US before a last-minute change of wording laid the groundwork for older adults to have access to a third dose.

The FDA’s adcomm on Vaccines and Related Biological Products (VRBPAC) roundly rejected Pfizer/BioNTech booster shots for all individuals older than 16 by a 16-2 vote Friday afternoon. Soon after, however, the agency posed committee members a new question limiting booster use to the 65-and-older population and individuals at high risk of disease due to occupational exposure or comorbidities.

Mi­rati's KRAS drug looks like the fa­vorite in colon can­cer with new da­ta, putting the pres­sure square on Am­gen

With Amgen already providing proof-of-concept for KRAS inhibitors with its sotorasib, Mirati Therapeutics is piecing together a follow-up effort in lung cancer with data it thinks are superior. But in colon cancer, where solo sotorasib has turned in a dud, Mirati may now have a strong case for superiority.

Mirati’s adagrasib, dosed solo or in combination with chemotherapy cetuximab, showed response rates grater than sotorasib solo  and as part of combination study in a similar patient population also revealed this week at #ESMO21. Mirati’s data were presented as part of a cohort update from the Phase II KRYSTAL-1 study testing adagrasib in a range of solid tumors harboring the KRAS-G12C mutation.

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The best of the rest: High­lights from the be­low-the-fold pre­sen­ta­tions at #ES­MO21

This year’s ESMO Congress has had a major focus on Big Pharma drugs — most notably candidates from Merck and AstraZeneca — but there have also been updates from smaller biotechs with data looking to challenge the big-name drugmakers.

Today, we’re highlighting some of the data releases that flew under the radar at #ESMO21 — whether from early-stage drugs looking to make a mark or older stalwarts with interesting follow-up data.

As­traZeneca, Dai­ichi Sanky­o's ADC En­her­tu blows away Roche's Kad­cy­la in sec­ond-line ad­vanced breast can­cer

AstraZeneca and Japanese drugmaker Daiichi Sankyo think they’ve struck gold with their next-gen ADC drug Enhertu, which has shown some striking data in late-stage breast cancer trials and early solid tumor tests. Getting into earlier patients is now the goal, starting with Enhertu’s complete walkover of a Roche drug in second-line breast cancer revealed Saturday.

Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared with Roche’s ADC Kadcyla in second-line unresectable and/or metastatic HER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo, according to interim data from the Phase III DESTINY-Breast03 head-to-head study presented at this weekend’s #ESMO21.

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Merck Research Laboratories CMO Roy Baynes

Mer­ck­'s Keytru­da un­corks full da­ta on lat­est ad­ju­vant win — this time in melanoma — adding bricks to ear­ly can­cer wall

In recent months, the battle for PD-(L)1 dominance has spilled over into early cancer with Merck’s Keytruda and Bristol Myers Squibb’s Opdivo all alone on the front lines. Keytruda now has another shell in its bandolier, and it could spell a quick approval.

Keytruda cut the risk of relapse or death by 35% over placebo (p=0.00658) in high-risk, stage 2 melanoma patients who had previously undergone surgery to remove their tumors, according to full data from the Phase III KEYNOTE-716 presented Saturday at #ESMO21.

Mer­ck flesh­es out Keytru­da win in first-line cer­vi­cal can­cer, adding more fire­pow­er to its ear­ly can­cer push

Merck has worked hard to bring its I/O blockbuster Keytruda into earlier and earlier lines of therapy, and now the wonder drug appears poised to make a quick entry into early advanced cervical cancer.

A combination of Keytruda and chemotherapy with or without Roche’s Avastin cut the risk of death by 33% over chemo with or without Avastin (p=<0.001) in first-line patients with persistent, recurrent or metastatic cervical cancer, according to full data from the Phase III KEYNOTE-826 study presented Saturday at #ESMO21.