Covid-19 roundup: South African vari­ant trips up Pfiz­er/BioN­Tech, Mod­er­na vac­cines while EU seeks an­ti-vari­ant con­tract claus­es — re­port

As ques­tions con­tin­ue to swirl about the ef­fec­tive­ness of cur­rent vac­cines against new vari­ants of the coro­n­avirus, a pair of let­ters to the ed­i­tor con­firm that those de­vel­oped by Pfiz­er/BioN­Tech and Mod­er­na ap­pear to be able to pro­tect against the UK vari­ant but less ef­fi­ca­cious when faced with the strain orig­i­nat­ing from South Africa.

Now that the first-gen­er­a­tion vac­cines’ ef­fi­ca­cy against the orig­i­nal SARS-CoV-2 anti­gen has large­ly been es­tab­lished, some sci­en­tists have turned their at­ten­tion to the ques­tions of when, where and how they can be best de­ployed.

The South African vari­ant has al­ready raised glob­al alarms af­ter As­traZeneca’s Ox­ford-part­nered vac­cine was side­lined af­ter it failed a small-scale analy­sis specif­i­cal­ly mea­sur­ing its ef­fi­ca­cy against B.1.351.

Writ­ing to the New Eng­land Jour­nal of Med­i­cine, two dif­fer­ent groups re­port­ed sim­i­lar find­ings about the serum neu­tral­iz­ing ac­tiv­i­ty elicit­ed by the Pfiz­er/BioN­Tech and Mod­er­na shots.

From the let­ter on BNT162b2:

Thus, as com­pared with neu­tral­iza­tion of USA-WA1/2020, neu­tral­iza­tion of Δ242-244+D614G virus was sim­i­lar and neu­tral­iza­tion of the B.1.351-spike virus was weak­er by ap­prox­i­mate­ly two thirds. Our da­ta are al­so con­sis­tent with poor­er neu­tral­iza­tion of the virus with the full set of B.1.351-spike mu­ta­tions than virus with ei­ther sub­set of mu­ta­tions and sug­gest­ed that virus with mu­tant residues in the re­cep­tor-bind­ing site (K417N, E484K, and N501Y) is more poor­ly neu­tral­ized than virus with Δ242-244, which is lo­cat­ed in the N-ter­mi­nal do­main of the spike pro­tein.

Mean­while with mR­NA-1273:

Both the full pan­el of mu­ta­tions in S and a sub­set of mu­ta­tions af­fect­ing the re­cep­tor-bind­ing do­main (RBD) re­gion of the B.1.1.7 vari­ant had no sig­nif­i­cant ef­fect on neu­tral­iza­tion by serum ob­tained from par­tic­i­pants who had re­ceived the mR­NA-1273 vac­cine in the phase 1 tri­al (Fig­ure 1A and 1B). In con­trast, we ob­served a de­crease in titers of neu­tral­iz­ing an­ti­bod­ies against the B.1.351 vari­ant and a sub­set of its mu­ta­tions af­fect­ing the RBD.

In a third let­ter, two Cana­di­an re­searchers sug­gest that the two dos­es of the Pfiz­er/BioN­Tech vac­cine should be giv­en at a longer in­ter­val than cur­rent­ly pre­scribed, based on a new analy­sis on the da­ta both com­pa­nies sub­mit­ted to the FDA.

One dose of the vac­cine, they ar­gue, is ac­tu­al­ly high­er than the 52.4% fig­ure that Phase III in­ves­ti­ga­tors had orig­i­nal­ly thought. If you re­move da­ta from the first two weeks af­ter the first dose, “when im­mu­ni­ty would have still been mount­ing,” the ef­fi­ca­cy would ac­tu­al­ly be much high­er.

“Even be­fore the sec­ond dose, BNT162b2 was high­ly ef­fi­ca­cious, with a vac­cine ef­fi­ca­cy of 92.6%, a find­ing sim­i­lar to the first-dose ef­fi­ca­cy of 92.1% re­port­ed for the mR­NA-1273 vac­cine (Mod­er­na),” they wrote. “Giv­en the cur­rent vac­cine short­age, post­pone­ment of the sec­ond dose is a mat­ter of na­tion­al se­cu­ri­ty that, if ig­nored, will cer­tain­ly re­sult in thou­sands of Covid-19–re­lat­ed hos­pi­tal­iza­tions and deaths this win­ter in the Unit­ed States — hos­pi­tal­iza­tions and deaths that would have been pre­vent­ed with a first dose of vac­cine.” — Am­ber Tong

EU seek­ing an­ti-vari­ant con­tract claus­es — re­port

With the emer­gence of new Covid-19 virus vari­ants and un­cer­tain­ty sur­round­ing vac­cines’ pro­tec­tion against them, the EU is re­port­ed­ly look­ing to en­sure ac­cess to po­ten­tial boost­er shots in its deals with vac­cine mak­ers.

The bloc is adding an­ti-vari­ant claus­es to new vac­cine sup­ply con­tracts and seek­ing to amend its old­er deals, Reuters re­port­ed, with lan­guage that ex­plic­it­ly cov­ers the vari­ants. The ne­go­ti­a­tions come amid the pub­li­ca­tion of stud­ies from Pfiz­er and Mod­er­na that sug­gest low­er an­ti­body lev­els against the South African vari­ant and South Africa it­self halt­ing roll­out of the As­traZeneca/Ox­ford vac­cine af­ter it showed high­ly di­min­ished ef­fi­ca­cy fight­ing the vari­ant in a small tri­al.

Three EU sources con­firmed the news to Reuters, with one of­fi­cial say­ing the claus­es would al­low the bloc to fo­cus on buy­ing up­grad­ed shots rather than vac­cines that are not ef­fec­tive against the wide­spread vari­ants. How­ev­er, the source added the de­f­i­n­i­tion of “vari­ant” in the new con­tracts re­mained vague, and it was un­clear what le­gal pow­er the con­tracts would give the EU.

All three con­firmed that one of these claus­es was in­clud­ed in the new EU con­tract with Pfiz­er and BioN­Tech signed ear­li­er this month. The deal is ex­pect­ed to sup­ply 300 mil­lion ad­di­tion­al dos­es of the pair’s mR­NA vac­cine.

In to­tal, the EU has se­cured deals to ac­quire rough­ly 2.6 bil­lion vac­cines from six com­pa­nies, and is still ne­go­ti­at­ing with No­vavax, Val­ne­va and Mod­er­na to pur­chase even more.

On Wednes­day af­ter­noon, Pfiz­er and Mod­er­na pub­lished re­search in the New Eng­land Jour­nal of Med­i­cine say­ing their vac­cines still of­fer enough pro­tec­tion to neu­tral­ize the South African vari­ant, but pro­duce sig­nif­i­cant­ly few­er an­ti­bod­ies in re­sponse. The study was con­duct­ed in a lab­o­ra­to­ry set­ting and it re­mains un­clear whether the same re­sponse would be seen in re­al life. — Max Gel­man

Mex­i­co fac­to­ry pro­duc­ing As­traZeneca shot al­most ful­ly up­grad­ed

Mex­i­co had been prepar­ing to pack­age and dis­trib­ute the As­traZeneca/Ox­ford vac­cine through­out Cen­tral Amer­i­ca, but that process had been held up by nec­es­sary fac­to­ry changes. Now, the coun­try is al­most ready to start.

The fac­to­ry up­grade had been held up by a se­ries of com­plex cer­ti­fi­ca­tion process­es af­ter health reg­u­la­tors could not de­ter­mine whether the plant could safe­ly pro­duce Covid-19 shots, Reuters re­port­ed. On an in­spec­tion vis­it to the fac­to­ry, which pre­vi­ous­ly made flu shots, of­fi­cials not­ed 185 “ob­ser­va­tions” that need­ed to be fixed.

“They al­most had to make an­oth­er fac­to­ry,” Mex­i­can for­eign min­is­ter Marce­lo Ebrard said at a gov­ern­ment news con­fer­ence, per Reuters. “You are talk­ing about health, life … so you do have to be very strict in any med­i­cine, with a vac­cine more, and even more when the vac­cine is so re­cent.”

Mex­i­co had re­ceived at least two ship­ments of As­traZeneca’s ac­tive vac­cine in­gre­di­ent but had not fin­ished pro­duc­ing dos­es of the shot. The fac­to­ry is now ex­pect­ed to start ship­ping the dos­es by ear­ly April, Ebrard said.

With the back­ing of Mex­i­can bil­lion­aire Car­los Slim, As­traZeneca had reached agree­ments with Mex­i­co and Ar­genti­na to dis­trib­ute their shots through­out the Cen­tral and South Amer­i­can re­gions. Mex­i­co al­so is aim­ing to speed up its vac­cine cam­paign, hav­ing im­port­ed 870,000 As­traZeneca shots from In­dia on Sun­day. — Max Gel­man

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

The DCT-OS: A Tech­nol­o­gy-first Op­er­at­ing Sys­tem - En­abling Clin­i­cal Tri­als

As technology-enabled clinical research becomes the new normal, an integrated decentralized clinical trial operating system can ensure quality, deliver consistency and improve the patient experience.

The increasing availability of COVID-19 vaccines has many of us looking forward to a time when everyday things return to a state of normal. Schools and teachers are returning to classrooms, offices and small businesses are reopening, and there’s a palpable sense of optimism that the often-awkward adjustments we’ve all made personally and professionally in the last year are behind us, never to return. In the world of clinical research, however, some pandemic-necessitated adjustments are proving to be more than emergency stopgap measures to ensure trial continuity — and numerous decentralized clinical trial (DCT) tools and methodologies employed within the last year are likely here to stay as part of biopharma’s new normal.

Angela Merkel (AP Photo/Michael Sohn)

Covid-19 roundup: Pfiz­er sub­mits vac­cine for full ap­proval; Merkel op­pos­es Biden pro­pos­al to sus­pend IP for vac­cines

Pfizer and BioNTech said Friday that they’ve submitted a biologics license application to the FDA for full approval of their mRNA vaccine for those over the age of 16.

How long it will take the FDA to decide on the BLA will be set once it’s been formally accepted by the agency.

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, previously told Endpoints News that the review of the BLA should take between three and four months, but it may be even faster than that.

Stéphane Bancel, Getty

Mod­er­na CEO brush­es off US sup­port for IP waiv­er, eyes more than $19B in Covid-19 vac­cine sales in 2021

Moderna is definitively more concerned with keeping pace with Pfizer in the race to vaccinate the world against Covid-19 than it is with Wednesday’s decision from the Biden administration to back an intellectual property waiver that aims to increase vaccine supplies worldwide.

In its first quarter earnings call on Thursday, Moderna CEO Stéphane Bancel shrugged off any suggestion that the newly US-backed intellectual property waiver would impact his company’s vaccine or bottom line. Still, the company’s stock price fell by about 9% in early morning trading.

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Onno van de Stolpe, Galapagos CEO (Thierry Roge/Belga Mag/AFP via Getty Images)

Gala­pa­gos chops in­to their pipeline, drop­ping core fields and re­or­ga­niz­ing R&D as the BD team hunts for some­thing 'trans­for­ma­tive'

Just 5 months after Gilead gutted its rich partnership with Galapagos following a bitter setback at the FDA, the Belgian biotech is hunkering down and chopping the pipeline in an effort to conserve cash while their BD team pursues a mission to find a “transformative” deal for the company.

The filgotinib disaster didn’t warrant a mention as Galapagos laid out its Darwinian restructuring plans. Forced to make choices, the company is ditching its IPF molecule ’1205, while moving ahead with a Phase II IPF study for its chitinase inhibitor ’4617.

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EMA safe­ty com­mit­tee seeks more in­fo on heart in­flam­ma­tion fol­low­ing Pfiz­er Covid-19 vac­cine

The European Medicines Agency’s safety committee said Friday that it’s aware of cases of inflammation of the heart muscle and inflammation of the membrane around the heart, mainly reported following vaccination with Pfizer’s Covid-19 vaccine, known in Europe as Comirnaty.

“There is no indication that these cases are due to the vaccine,” the EMA’s Pharmacovigilance Risk Assessment Committee said.

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An­oth­er failed tri­al for Or­p­hazyme's 'pipeline-in-a-pro­duc­t' leaves shad­ow on drug's fu­ture

The tumultuous ride for Orphazyme continued on Friday as the company announced that a pivotal trial for its lead drug arimoclomol failed yet again, this time in the treatment of ALS, seeding doubt in a drug that had recently been cleared by the FDA for priority review. The latest failure casts a darker shadow on the upcoming decision despite Orphazyme’s upbeat outlook.

In a statement, the Danish biotech announced that the drug did not meet its primary or secondary endpoints evaluating function and survival. But the company has not announced any data surrounding the failure, instead saying that it will publish the complete results later this year.

In­cyte ponies up $12M to set­tle char­i­ty foun­da­tion kick­back claims; US ex­er­cis­es op­tion for more dos­es of mon­key­pox vac­cine

One in a string of lawsuits targeting copay charity foundations, the DOJ has been hunting drugmaker Incyte for what prosecutors alleged was a kickback scheme to court patients. Now, Incyte is clearing its name.

Incyte will shell out $12.6 million to settle claims it funneled funds through a charity foundation to cover federal copays for patients taking its JAK inhibitor Jakafi, the DOJ said this week.

CEO Khurem Farooq (Gyroscope)

Hours be­fore ex­pect­ed de­but, Gy­ro­scope post­pones its IPO as 2 oth­er biotechs hold the line on their march to Nas­daq

Editor’s note: Interested in following biopharma’s fast-paced IPO market? You can bookmark our IPO Tracker here.

In a surprising turn of events, UK-based Gyroscope Therapeutics has postponed its IPO mere hours before it was set to debut on Nasdaq.

Working on a gene therapy for wet AMD, Gyroscope was all set and ready to go public earlier this week, setting terms for a $142 million raise with a price range of $20 to $22. But in the wee hours of Friday morning, the company put out a press release saying they would delay their debut “in light of market conditions,” CEO Khurem Farooq said in a statement.

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Karyopharm taps long­time Pfiz­er, Am­gen vet to steer the ship; With Mer­ck in the rearview mir­ror, Roger Perl­mut­ter stakes his claim to a CEO job — and it's a sur­pris­ing choice

Like many who work in biopharma, Richard Paulson got started in the field because of a love of science.

Paulson had just finished business school and was looking to start a career that married his two passions. While looking for jobs, he thought of his grandmother who had struggled with Alzheimer’s disease, recalling how he saw first-hand what innovative medicines can do for patients. Ultimately, he started his first job in the space as a sales rep at Glaxo Wellcome, one of GlaxoSmithKline’s predecessors before its merger with SmithKline Beecham in 2000.