(AP Photo/Virginia Mayo)

Up­dat­ed: Study iden­ti­fies Covid-19 pa­tients with mu­ta­tions in­di­cat­ing remde­sivir re­sis­tance

As the bi­va­lent boost­er sea­son kicks off in earnest, a new study pub­lished yes­ter­day from NYU re­searchers iden­ti­fies two cas­es of mu­tat­ed coro­n­avirus re­sis­tant to Gilead’s remde­sivir in im­muno­com­pro­mised in­di­vid­u­als.

The two pa­tients in their 50s and 60s had both un­der­gone kid­ney trans­plants (and were both vac­ci­nat­ed pri­or to those trans­plants), with one ex­pe­ri­enc­ing Covid for sev­er­al months while re­ceiv­ing rit­ux­imab and ben­damus­tine for lym­phoma.

“The com­bined ef­fect of these mu­ta­tions may lim­it the clin­i­cal ef­fi­ca­cy of remde­sivir,” the re­searchers wrote, adding:

remde­sivir use has be­come wide­spread, and we show that mu­ta­tions as­so­ci­at­ed with remde­sivir re­sis­tance arise in vi­vo, our work em­pha­sizes sur­veil­lance ef­forts to de­tect mu­ta­tions in im­muno­com­pro­mised pa­tients. Po­ten­tial­ly fore­shad­ow­ing an “end-game” sce­nario for the COVID-19 pan­dem­ic, com­plex cas­es like the ones we de­scribe high­light the need for more ad­vanced mol­e­c­u­lar di­ag­nos­tics at the on­set of ill­ness to guide ther­a­peu­tic de­ci­sions. Ad­di­tion­al­ly, our work em­pha­sizes the risk of im­mune es­cape in im­muno­com­pro­mised hosts, with nov­el mu­ta­tions con­tribut­ing to re­crude­s­cence of in­fec­tion. Equal­ly con­cern­ing are re­cent re­ports in im­muno­com­pro­mised hosts high­light­ing the de­vel­op­ment of SARS-CoV-2 spike mu­ta­tions con­fer­ring re­sis­tance to im­munother­a­peu­tics af­ter treat­ment with mon­o­clon­al an­ti­bod­ies.

First ful­ly ap­proved by FDA in Oc­to­ber 2020, remde­sivir has proven to be a block­buster, pulling in more than $5.5 bil­lion last year, but un­like oth­er Covid block­buster ther­a­peu­tics (e.g. Re­gen­eron’s mAb and Lil­ly’s mAb com­bo treat­ment) remde­sivir has man­aged to stay ef­fec­tive with each new vari­ant so far.

Gilead said in an emailed state­ment that it

has re­viewed a re­port of a re­sis­tance mu­ta­tion (V792I) in the vi­ral RNA poly­merase, the tar­get of remde­sivir, which oc­curred in two hos­pi­tal­ized re­nal trans­plant re­cip­i­ents with se­vere­ly com­pro­mised im­mune func­tion and chron­ic SARS-CoV-2 in­fec­tion, af­ter re­peat­ed remde­sivir ex­po­sure. One pa­tient had high viremia (pres­ence of a virus in the blood) and was treat­ed with a 5-day course of remde­sivir 6 months af­ter trans­plant and an­oth­er 5-day course up­on read­mis­sion 24 days af­ter ini­tial COVID-19 di­ag­no­sis. The sec­ond pa­tient had high viremia and was treat­ed with a 3-day course of remde­sivir four­teen months af­ter trans­plant and an­oth­er 5-day course up­on read­mis­sion 18 days af­ter ini­tial COVID-19 di­ag­no­sis. It is known that unchecked, pro­longed vi­ral repli­ca­tion in pa­tients with im­muno­com­pro­mised sta­tus can re­sult in vi­ral ge­net­ic di­ver­si­ty with­in such in­di­vid­u­als and proac­tive ther­a­py is war­rant­ed in pa­tients re­quir­ing hos­pi­tal­iza­tion. It is in the best in­ter­est of pa­tients to treat SARS-CoV-2 in­fec­tion as soon as pos­si­ble and, as the ar­ti­cle sug­gests, fur­ther ef­forts are need­ed to iden­ti­fy con­cern­ing mu­ta­tions con­fer­ring re­sis­tance to SARS-CoV-2 ther­a­peu­tics and ad­dress their clin­i­cal im­pli­ca­tions. The V792I mu­ta­tion has been pre­vi­ous­ly iden­ti­fied in an in vit­ro se­lec­tion study, which showed that this mu­ta­tion alone re­duces the an­tivi­ral ac­tiv­i­ty of remde­sivir by 2.6-fold, in­di­cat­ing that oth­er mu­ta­tions might be re­quired to fur­ther re­duce the sen­si­tiv­i­ty of virus to the drug.

But in vit­ro stud­ies in­di­cate that Vek­lury (remde­sivir) con­tin­ues to be ac­tive against Omi­cron vari­ants in­clud­ing the cur­rent BA.4 and BA.5, Gilead said, adding that at this time, more than half of pa­tients hos­pi­tal­ized with Covid in the US are treat­ed with Vek­lury and it is ap­proved or au­tho­rized for tem­po­rary use in ap­prox­i­mate­ly 50 coun­tries world­wide.

Susan Galbraith, AstraZeneca EVP, oncology R&D, at EUBIO22 (Rachel Kiki for Endpoints News)

Up­dat­ed: As­traZeneca jumps deep­er in­to cell ther­a­py 2.0 space with $320M biotech M&A

Right from the start, the execs at Neogene had some lofty goals in mind when they decided to try their hand at a cell therapy that could tackle solid tumors.

Its founders have helped hone a new approach that would pack in multiple neoantigen targets to create a personalized TCR treatment that would not just make the leap from blood to solid tumors, but do it with durability. And they managed to make their way rapidly to the clinic, unveiling their first Phase I program for advanced tumors just last May.

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Ei­sai’s ex­pand­ed Alzheimer’s da­ta leave open ques­tions about safe­ty and clin­i­cal ben­e­fit

Researchers still have key questions about Eisai’s investigational Alzheimer’s drug lecanemab following the publication of more Phase III data in the New England Journal of Medicine Tuesday night.

In the paper, which was released in conjunction with presentations at an Alzheimer’s conference, trial investigators write that a definition of clinical meaningfulness “has not been established.” And the relative lack of new information, following topline data unveiled in September, left experts asking for more — setting up a potential showdown to precisely define how big a difference the drug makes in patients’ lives.

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Illustration: Assistant Editor Kathy Wong for Endpoints News

Twit­ter dis­ar­ray con­tin­ues as phar­ma ad­ver­tis­ers ex­tend paus­es and look around for op­tions, but keep tweet­ing

Pharma advertisers on Twitter are done — at least for now. Ad spending among the previous top spenders flattened even further last week, according to the latest data from ad tracker Pathmatics, amid ongoing turmoil after billionaire boss Elon Musk’s takeover now one month ago.

Among 18 top advertisers tracked for Endpoints News, only two are spending: GSK and Bayer. GSK spending for the full week through Sunday was minimal at just under $1,900. Meanwhile, German drugmaker Bayer remains the industry outlier upping its spending to $499,000 last week from $480,000 the previous week. Bayer’s spending also marks a big increase from a month ago and before the Musk takeover, when it spent $16,000 per week.

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Vi­a­tris with­draws ac­cel­er­at­ed ap­proval for top­i­cal an­timi­cro­bial 24 years lat­er

After 24 years without confirming clinical benefit, the FDA announced Tuesday morning that Viatris (formed via Mylan and Pfizer’s Upjohn) has decided to withdraw a topical antimicrobial agent, Sulfamylon (mafenide acetate), after the company said conducting a confirmatory study was not feasible.

Sulfamylon first won FDA’s accelerated nod in 1998 as a topical burn treatment, with the FDA noting that last December, Mylan told the agency that it wasn’t running the trial.

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Catal­ent to cut about 200 jobs in Mary­land and Texas

Contract manufacturing company Catalent is cutting about 200 jobs in Maryland and Texas, according to WARN notices, trimming back some of its pandemic-era expansion.

The company will cut 77 jobs by Jan. 15 of next year at a cell therapy facility in Webster, TX, just outside of Houston. In Maryland, the company is reducing staff at two locations, with 82 jobs being eliminated at Catalent’s facility in Gaithersburg, and 53 in Rockville. The layoffs go into effect at those locations on Jan. 14.

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iECURE CEO Joe Truitt and founder Jim Wilson

Jim Wil­son biotech iECURE gets fresh $65M to push pe­di­atric liv­er dis­ease gene ther­a­py in­to the clin­ic

Jim Wilson-founded biotech iECURE has wrapped a $65M Series A extension round to get its lead candidate — a gene replacement therapy for a rare inherited liver disease known as ornithine transcarbamylase deficiency, or OTC — into the clinic.

This round was co-led by Novo Holdings and LYFE Capital, followed by initial investors Versant and OrbiMed as well. In September 2021, iECURE raised a $50 million Series A led by the latter two. The new cash infusion will get iECURE through an initial in-human trial, which CEO Joe Truitt told Endpoints News iECURE hopes to read out in 2024.

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Tim Walbert, Horizon Therapeutics CEO (via YouTube)

Hori­zon Ther­a­peu­tics in takeover talks with Am­gen, J&J, Sanofi as po­ten­tial buy­ers

Amgen, J&J’s Janssen and Sanofi are all in talks to acquire Horizon Therapeutics, the rare disease biotech disclosed late Tuesday.

Horizon confirmed “highly preliminary discussions” with those companies regarding a potential buyout offer after the Wall Street Journal reported takeover interest.

Although the company — which commands a market cap of close to $18 billion — emphasized that “there can be no certainty that any offer will be made for the Company,” shares $HZNP still surged 31% in after-hours trading to near $103, bringing it to the point where it started the year.

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Sana, Codex­is lay off staff, reshuf­fle pipeline in bid to fo­cus cell ther­a­py, en­zyme en­gi­neer­ing work

As its market cap shrinks to a fraction of its heyday, flashy cell therapy startup Sana Biotechnology is laying off 15% of its staffers in a move to rejig the pipeline and restructure the company.

Sana is among a growing group of biotechs that, feeling the weight of a broader market downturn and seeing their shares tumble steadily, are tightening the purse strings and adjusting their focus. Also on Tuesday, Codexis, an enzyme engineering company based in California and now helmed by former Sierra Oncology CEO Stephen Dilly, announced it will reduce the workforce by 18%.

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John Carroll with David Chang, Allogene CEO (Credit: Jeff Rumans Photography)

Al­lo­gene takes the stage in New York to go deep on its off-the-shelf cell ther­a­pies — de­clar­ing a first for sol­id tu­mors

NEW YORK — In most cases, a biotech like Allogene would wait until the next big science conference to offer its latest series of snapshots of its data. But most biotechs aren’t like Allogene, where the veteran leaders from Kite garnered a substantial number of kudos over the years for their in-depth reviews of the company’s progress.

So on Tuesday, the leaders at Allogene converged on Manhattan once again to give a detailed breakdown of their latest steps forward, looking to stay out front in the busy off-the-shelf cell therapy arena, keep a clean bill of health on the safety front and prove that they can not only match the autologous pioneers they helped create but make the all-important leap into solid tumors. It’s another step forward in a journey that has a long way to go before even the first big regulatory finish lines appear on the track. But for CEO David Chang, who spent some time with me running through the data ahead of the Tuesday session, it all amounts to forward momentum toward the desired goal.

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