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.

Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Glax­o­SmithK­line re­thinks strat­e­gy for Covid-19 an­ti­body — not the Vir ones — af­ter tri­al flop. Is there hope in high-risk pa­tients?

In the search for a better Covid-19 therapeutic, GlaxoSmithKline and Vir have partnered up on two antibodies they hope have a chance. GSK is also testing its own in-house antibody, and early results may have shut the door on its widespread use.

A combination of GSK’s monoclonal antibody otilimab plus standard of care couldn’t best standard of care alone in preventing death and respiratory failure in hospitalized Covid-19 patients after 28 days, according to data from the Phase IIa OSCAR study unveiled Thursday.

Steve Cutler, Icon CEO (Icon)

In the biggest CRO takeover in years, Icon doles out $12B for PRA Health Sci­ences to fo­cus on de­cen­tral­ized clin­i­cal work

Contract research M&A had a healthy run in recent years before recently petering out. But with the market ripe for a big buyout and the Covid-19 pandemic emphasizing the importance of decentralized trials, Wednesday saw a tectonic shift in the CRO world.

Icon, the Dublin-based CRO, will acquire PRA Health Sciences for $12 billion in a move that will shake up the highest rungs of a fragmented market. The merger would combine the 5th- and 6th-largest CROs by 2020 revenue, according to Icon, and the merger will set the newco up to be the second-largest global CRO behind only IQVIA.

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Tom Barnes (Orna)

The mR­NA era is here. MPM be­lieves the fu­ture be­longs to oR­NA — and Big Phar­ma wants a seat at the ta­ble

If the ultra-fast clinical development of Covid-19 vaccines opened the world’s eyes to the promises of messenger RNA, the subsequent delays in supply offered a crash course on the ultra-complex process of producing them. Even before the formulation and fill-finish steps, mRNA is the precious end product from an arduous journey involving enzyme-aided transcription, modification and purification.

For Bristol Myers Squibb, Novartis Institutes for Biomedical Research, Gilead’s Kite and Astellas, it’s time to rethink the way therapeutic RNA is engineered.

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Tal Zaks, Moderna CMO (AP Photo/Rodrique Ngowi, via still image from video)

CMO Tal Zaks bids Mod­er­na a sur­prise adieu as biotech projects $18.4B in rev­enue, plots post-Covid ex­pan­sion

How do you exit a company after six years in style? Developing one of the most lucrative and life-saving products in pharma history is probably not the worst way to go.

Tal Zaks, Moderna’s CMO since 2015, will leave the mRNA biotech in September, the biotech disclosed in their annual report this morning. The company has already retained the recruitment firm Russell Reynolds to find a replacement.

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Mod­er­na's Stéphane Ban­cel plans to dou­ble down on vac­cine pro­duc­tion, new vari­ants as mR­NA rules in pan­dem­ic fight

Stéphane Bancel thought he’d be sleeping more by now.

The 48-year-old Moderna CEO figured that by 2021 he’d have his vaccine through the clinic, authorized, and in mass production — that the hard part would be over. Instead, he’s still working Saturdays and Sundays, talking with his lab and manufacturing teams and fielding calls with two to three world leaders a day to answer their concerns about supply and emerging new variants.

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Re­gen­eron halts place­bo en­roll­ment in Covid-19 cock­tail tri­al af­ter IDMC finds 'clear' ef­fi­ca­cy — but there are no da­ta yet

Despite having already received an emergency use authorization for its Covid-19 antibody in non-hospitalized patients last November, Regeneron continued to conduct trials to evaluate the cocktail’s effectiveness. Now, the big biotech has received some good news from their IDMC.

On the IDMC’s recommendation, Regeneron will be shutting down enrollment in the placebo group of a Phase III outpatient trial for their REGN-COV program — a mix of casirivimab with imdevimab — after investigators found “clear clinical efficacy” in both doses compared to the control, the company announced Thursday. CSO George Yancopoulos also said in a statement that the cocktail can neutralize emerging strains of the novel coronavirus.

S&P ex­pects steady ero­sion in Big Phar­ma's cred­it pro­file in 2021 as new M&A deals roll in — but don't un­der­es­ti­mate their un­der­ly­ing strength

S&P Global has taken a look at the dominant forces shaping the pharma market and come to the conclusion that there will be more downgrades than upgrades in 2021 — the 8th straight year of steady decline.

But it’s not all bad news. Some things are looking up, and there’s still plenty of money to be made in an industry that enjoys a 30% to 40% profit margin, once you factor in steep R&D expenses.