UP­DAT­ED: Ea­ger to re­deem its Covid-19 vac­cine, As­traZeneca touts 82.4% ef­fi­ca­cy for 12-week dos­ing sched­ule — but will the FDA buy it?

As­traZeneca and Ox­ford say they now have clin­i­cal ev­i­dence that dos­ing their ade­n­ovirus-based Covid-19 vac­cine 12 weeks apart — a reg­i­men ap­proved by the UK, per­plex­ing many — can ac­tu­al­ly ren­der the shots more ef­fec­tive.

The da­ta will be key to As­traZeneca’s at­tempt to pull it­self back to the up­per ranks of the vac­cine hi­er­ar­chy, where it’s strug­gled as skep­tics poke holes in its ef­fi­ca­cy while pro­duc­tion de­lays trig­ger heat­ed dis­putes with the EU. But it re­mains to be seen what im­pact, if any, the analy­sis will have on the FDA’s think­ing and de­ci­sions re­gard­ing the vac­cine.

The new re­sults draw from the same Phase III study, con­duct­ed in the UK, Brazil and South Africa, whose in­ter­im da­ta ce­ment­ed the first au­tho­riza­tions of the vac­cine, but in­clude 332 cas­es of Covid-19 (com­pared to 131 at the ini­tial cut).

In­ves­ti­ga­tors wrote in a preprint on the Lancet:

In our study, vac­cine ef­fi­ca­cy was high­er, af­ter the sec­ond dose, in those with a longer prime-boost in­ter­val, reach­ing 82.4% in those with a dos­ing in­ter­val of 12 weeks or more. Point es­ti­mates of ef­fi­ca­cy were low­er with short­er dos­ing in­ter­vals, though it should be not­ed that there is some un­cer­tain­ty as con­fi­dence in­ter­vals over­lap. High­er bind­ing and neu­tral­is­ing an­ti­body titres were ob­served in sera at the longer prime-boost in­ter­val, sug­gest­ing that, as­sum­ing there is a re­la­tion­ship be­tween the hu­moral im­mune re­sponse and ef­fi­ca­cy, these may be true find­ings and not arte­facts of the da­ta.

In to­tal, 1293 par­tic­i­pants (out of 17,177 in­clud­ed for this analy­sis) were giv­en two full dos­es of the vac­cine 12 weeks apart.

If true, it con­firms ear­li­er sug­ges­tions by As­traZeneca ex­ecs — backed by some sci­en­tists — that the 12-week in­ter­val is the “win­ning for­mu­la” for get­ting ef­fi­ca­cy near the lev­els of the Pfiz­er/BioN­Tech or Mod­er­na vac­cines.

While there’s still some dis­tance be­tween 82.4% and 95% (as re­port­ed by the mR­NA play­ers), the dif­fer­ence is no­tably small­er than when in­ves­ti­ga­tors ob­served a 62% ef­fi­ca­cy for two full-dose reg­i­men, ad­min­is­tered 4 weeks apart.

Will it mat­ter out­side of the UK and the EU, where the au­thor­i­ties al­ready rec­om­mend the longer dose sched­ule?

Bio­phar­ma R&D chief Mene Pan­ga­los ad­mit­ted in a me­dia brief­ing Wednes­day morn­ing that the US Phase III tri­al, which he be­lieves the com­pa­ny needs to com­plete be­fore seek­ing an emer­gency use au­tho­riza­tion from the FDA, on­ly tests the 4-week dose in­ter­val. The la­bel and rec­om­mend­ed im­ple­men­ta­tion is a whole oth­er mat­ter.

“Ob­vi­ous­ly we do want the FDA and reg­u­la­tors to be in­formed by our da­ta on in­ter-dose in­ter­vals from our oth­er glob­al stud­ies,” he added.

In­ter­est­ing­ly, in­ves­ti­ga­tors pro­posed that the longer dos­ing sched­ule may be some­what re­spon­si­ble for the ear­ly sub­group analy­sis that found a low dose fol­lowed by a high dose — giv­en to around 8,000 vol­un­teers by er­ror — was much more ef­fec­tive, boost­ing ef­fi­ca­cy to 90%.

“This find­ing is con­firmed in the cur­rent analy­sis, but with fur­ther da­ta avail­able, we show that the en­hanced im­muno­genic­i­ty and ef­fi­ca­cy with this reg­i­men may be part­ly dri­ven by the longer dos­ing in­ter­val that was a fea­ture of this group, fur­ther sup­port­ing the ob­ser­va­tion of a re­la­tion­ship be­tween dose in­ter­val and ef­fi­ca­cy in the SD/SD group dis­cussed above and sup­port­ed by emer­gency use au­tho­ri­sa­tion,” they wrote, adding: “The SD/SD reg­i­men is pre­ferred op­er­a­tional­ly as it is more straight­for­ward to de­liv­er a vac­cine with one dosage, and be­cause there are more im­muno­genic­i­ty and ef­fi­ca­cy da­ta to sup­port its use.”

As­traZeneca has pre­vi­ous­ly said it would con­duct a new tri­al to test that reg­i­men, but they have now dropped that plan to fo­cus on the longer in­ter­val and next-gen­er­a­tion can­di­dates.

“Our am­bi­tion is to be ready for the next round of im­mu­niza­tions that may be nec­es­sary as we go in­to next win­ter,” he said. “That’s what we’re aim­ing for.”

Add that to the new­ly re­port­ed num­ber that the As­traZeneca vac­cine is 76% ef­fec­tive af­ter just one shot, and it’s al­so a boon for coun­tries that are scram­bling to put vac­cines in arms, giv­ing them more time to sort out the first dos­es for more peo­ple be­fore hav­ing to wor­ry about the sec­ond dose.

The com­pa­ny added that new da­ta con­firmed that its vac­cine could pre­vent hos­pi­tal­iza­tions or se­vere cas­es, reach­ing 100% pro­tec­tion if you start count­ing 10 days af­ter the first dose. In the same pe­ri­od, the con­trol group saw 22 such events.

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.

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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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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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.

UP­DAT­ED: 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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As­traZeneca caps PD-L1/CT­LA-4/chemo com­bo come­back with OS win. Is treme­li­mum­ab fi­nal­ly ready for ap­proval?

AstraZeneca’s closely-watched POSEIDON study continues to be the rare bright spot in its push for an in-house PD-L1/CTLA-4 combo.

Combining Imfinzi and tremelimumab with physicians’ choice of chemotherapy helped patients with stage IV non-small cell lung cancer live longer, the company reported — marking the first time the still-experimental tremelimumab has demonstrated an OS benefit.

For AstraZeneca and CEO Pascal Soriot, the positive readout — which is devoid of numbers — offers much-needed validation for the big bet they made on Imfinzi plus tremelimumab, after the PD-L1/CTLA-4 regimen failed multiple trials in head and neck cancer as well as lung cancer.

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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.

Ron DePinho (file photo)

A 'fly­over' biotech launch­es in Texas with four Ron De­Pin­ho-found­ed com­pa­nies un­der its belt

In his 13 years at Genzyme, Michael Wyzga noticed something about East Coast drugmakers. Execs would often jet from Boston or New York to San Francisco to find more assets, and completely miss the work being done in flyover states, like Texas or Wisconsin.

“If it doesn’t come out of MGH or MIT or Harvard, probably not that interesting,” he said of the mindset.

Now, he and some well-known industry players are looking to change that, and they’ve reeled in just over $38 million to do it.

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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.