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.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

Bio­gen hit by ALS set­back with PhI­II fail­ure for tofersen — but fol­lows a fa­mil­iar strat­e­gy high­light­ing the pos­i­tive

Patients and analysts waiting to hear Sunday how Biogen’s SOD1-ALS drug tofersen fared in Phase III didn’t have to wait long for the top-line result they were all waiting for. The drug failed the primary endpoint on significantly improving the functional and neurologic decline of patients over 28 weeks as well as the extension period for continued observation.

In fact, there was very little difference in response.

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UP­DAT­ED: Boehringer nabs FDA's first in­ter­change­abil­i­ty des­ig­na­tion for its Hu­mi­ra com­peti­tor — but will it mat­ter?

The FDA late Friday awarded Boehringer Ingelheim the first interchangeability designation for its Humira biosimilar Cyltezo, meaning that when it launches in July 2023, pharmacists will be able to automatically substitute the Boehringer’s version for AbbVie’s mega-blockbuster without a doctor’s input.

The designation will likely give Boehringer, which first won approval for Cyltezo in 2017, the leg up on a crowded field of Humira competitors.

Reshma Kewalramani, Vertex CEO (YouTube)

Ver­tex gets much-need­ed win with ‘ex­tra­or­di­nary’ first pa­tient re­sults on po­ten­tial di­a­betes cure

Vertex said Monday that the first patient dosed with its cell therapy for type 1 diabetes saw their need for insulin injections vanish almost entirely, a key early step in the decades-long effort to develop a curative treatment for the chronic disease.

The patient, who had suffered five potentially life-threatening hypoglycemic — or low blood sugar — episodes in the year before the therapy, was injected with synthetic insulin-producing cells. After 90 days, the patient’s new cells produced insulin steadily and ramped up their insulin production after a meal like normal cells do, as measured by a standard biomarker for insulin production.

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No­var­tis de­vel­op­ment chief John Tsai: 'We go deep in the new plat­form­s'

During our recent European Biopharma Summit, I talked with Novartis development chief John Tsai about his experiences over the 3-plus years he’s been at the pharma giant. You can read the transcript below or listen to the exchange in the link above.

John Carroll: I followed your career for quite some time. You’ve had more than 20 years in big pharma R&D and you’ve obviously seen quite a lot. I really was curious about what it was like for you three and a half years ago when you took over as R&D chief at Novartis. Obviously a big move, a lot of changes. You went to work for the former R&D chief of Novartis, Vas Narasimhan, who had his own track record there. So what was the biggest adjustment when you went into this position?

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Thomas Lingelbach, Valneva CEO

Small biotech says its Covid-19 vac­cine spurs more an­ti­bod­ies than As­traZeneca’s. Will sup­ply deals come now?

In a first, a small runner-up vaccine developer says its own Covid-19 jab has induced “superior neutralizing antibody titer levels” over AstraZeneca’s AZD1222 when pitted head-to-head in a Phase III trial.

That and non-inferiority in seroconversion rate were the co-primary endpoints of the trial, which recruited 4,012 adult volunteers across the UK.

But on the exploratory endpoint of Covid-19 case counts, Valneva notes that both treatment groups saw a similar number of infections.

Susan Galbraith, Executive VP, Oncology R&D, AstraZeneca

As­traZeneca on­col­o­gy R&D chief Su­san Gal­braith: 'Y­ou're go­ing to need or­thog­o­nal com­bi­na­tion­s'


Earlier in the week we broadcast our 4th annual European Biopharma Summit with a great lineup of top execs. One of the one-on-one conversations I set up was with Susan Galbraith, the oncology research chief at AstraZeneca. In a wide-ranging discussion, Galbraith reviewed the cancer drug pipeline and key trends influencing development work at the pharma giant. You can watch the video, above, or stick with the script below. — JC

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Two drug­mak­ers hit with PDU­FA date de­lays from FDA amid back­log of in­spec­tions

As the FDA is weighed down with more and more pandemic responsibilities, the agency is beginning to miss PDUFA dates with more frequency too. Two different companies on Monday said they received notices that the FDA has not completed their drug reviews on time.

The review of an NDA for Avadel Pharmaceuticals’ candidate treatment for narcolepsy is not coming this month, the company said, and the review of UCB’s BLA for bimekizumab, used to treat moderate to severe plaque psoriasis, will miss its target date as well.

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Terrie Curran, Phathom CEO (Credit: Arcutis)

Phath­om's old Take­da drug bests Pre­vacid in a PhI­II GI tri­al. Next stop? The FDA

There’s no time for rest in biopharma — at least not at Phathom Pharmaceuticals. Just over a month after submitting two NDAs for its lead acid-fighter vonoprazan, the biotech is already lining up a third, and collecting an extra $50 million to push things along.

Vonoprazan met its primary non-inferiority endpoints in a Phase III study comparing it to standard-of-care Prevacid in a type of gastroesophageal reflux disease (GERD) called erosive esophagitis (EE). It also proved superior to the popular heartburn drug by multiple measures, including healing rate and maintenance of healing.