As­traZeneca pub­lish­es Covid-19 vac­cine PhI­II pro­to­cols in lock­step with Mod­er­na and Pfiz­er. How are they dif­fer­ent?

Fol­low­ing in the steps of Mod­er­na and Pfiz­er, the oth­er two Amer­i­can drug­mak­ers cur­rent­ly in Phase III tri­als for their Covid-19 vac­cines, As­traZeneca post­ed its own study pro­to­cols over the week­end. The move is the lat­est in a se­ries of rare peeks be­hind the cur­tain, as such blue­prints are typ­i­cal­ly shared once such tri­als are com­plet­ed.

“Giv­en the un­prece­dent­ed glob­al im­pact of the Coro­n­avirus pan­dem­ic and the need for pub­lic in­for­ma­tion, As­traZeneca has pub­lished the de­tailed pro­to­col and de­sign of our AZD1222 clin­i­cal tri­al. As with most clin­i­cal de­vel­op­ment, pro­to­cols are not typ­i­cal­ly shared pub­licly due to the im­por­tance of main­tain­ing con­fi­den­tial­i­ty and in­tegri­ty of tri­als. As­traZeneca con­tin­ues to work with in­dus­try peers to en­sure a con­sis­tent ap­proach to shar­ing time­ly clin­i­cal tri­al in­for­ma­tion,” the com­pa­ny said in a state­ment.

As­traZeneca’s tri­al, un­like the ones from coun­ter­parts, on­ly plans for one in­ter­im analy­sis that could al­low the com­pa­ny to stop the tri­al ear­ly and pe­ti­tion for an emer­gency use au­tho­riza­tion. That analy­sis is ex­pect­ed to oc­cur at 75 in­fec­tions. Mod­er­na ex­pects two analy­ses, at 53 and 106 events, while Pfiz­er pen­ciled in four — at 32, 62, 92 and 120 cas­es.

The British phar­ma al­so in­di­cat­ed that it is aim­ing for a 50% ef­fi­ca­cy rate for its can­di­date, the thresh­old that the FDA has set for in its coro­n­avirus vac­cine guide­lines, where­as Mod­er­na and Pfiz­er are both aim­ing for 60% ef­fec­tive­ness.

All three com­pa­nies al­so have dif­fer­ent cri­te­ria for symp­toms in the pri­ma­ry end­points of their tri­als, with each in­clud­ing those as­so­ci­at­ed with mild in­fec­tions. Er­ic Topol, one of the in­dus­try’s strongest ad­vo­cates for vac­cine trans­paren­cy, sum­ma­rized those dif­fer­ences in a tweet.

Vac­cine mak­ers have been un­der in­tense po­lit­i­cal pres­sure through­out the Covid-19 pan­dem­ic, but that has on­ly ramped up as No­vem­ber’s pres­i­den­tial elec­tion draws near­er. Pres­i­dent Don­ald Trump has re­peat­ed­ly of­fered promis­es that a vac­cine could be ready be­fore the elec­tion, and HHS sec­re­tary Alex Azar ef­fec­tive­ly set the FDA staff on no­tice say­ing that his sig­na­ture is re­quired on all rule mak­ing.

Thus far, Pfiz­er CEO Al­bert Bourla has been the on­ly ex­ec­u­tive to say his com­pa­ny could know whether or not its vac­cine works in Oc­to­ber. Mod­er­na pres­i­dent Stephen Hoge, ap­pear­ing on CBS Evening News last week, said the drug­mak­er could know if its own vac­cine works by No­vem­ber.

De­spite a green light to re­sume in the UK, As­traZeneca’s Phase III tri­al re­mains on hold in the US af­ter a vol­un­teer in the UK de­vel­oped a con­di­tion thought to be trans­verse myelitis, a rare spinal in­flam­ma­tion dis­or­der, af­ter tak­ing their sec­ond dose of the vac­cine. The com­pa­ny has not con­firmed the di­ag­no­sis, and a doc­u­ment post­ed by Ox­ford Uni­ver­si­ty last week sug­gest­ed that the vac­cine was not linked to the con­di­tion.

That in­stance was the sec­ond time As­traZeneca’s tri­al was placed on hold fol­low­ing a case of un­di­ag­nosed mul­ti­ple scle­ro­sis oc­cur­ring in a sep­a­rate tri­al par­tic­i­pant.

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

What Will it Take to Re­al­ize the Promise and Po­ten­tial of Im­mune Cell Ther­a­pies?

What does it take to get to the finish line with a new cancer therapy – fast? With approvals in place and hundreds of immune cell therapy candidates in the pipeline, the global industry is poised to create a fundamental shift in cancer treatments towards precision medicine. At the same time, unique challenges associated with cell and process complexity present manufacturing bottlenecks that delay speed to market and heighten cost of goods sold (COGS) — these hurdles must be overcome to make precision treatments an option for every cancer patient. This series of articles highlights some of the key manufacturing challenges associated with the production of cell-based cancer therapies as well as the solutions needed to transcend them. Automation, process knowledge, scalability, and assured supply of high-quality starting material and reagents are all critical to realizing the full potential of CAR-based therapies and sustaining the momentum achieved in recent years. The articles will highlight leading-edge technologies that incorporate these features to integrate across workflows, accelerate timelines and reduce COGS – along with how these approaches are enabling the biopharmaceutical industry to cross the finish line faster with new treatment options for patients in need.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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President Biden and Pfizer CEO Albert Bourla (Patrick Semansky/AP Images)

Chaot­ic ad­comm sees Pfiz­er/BioN­Tech boost­ers re­ject­ed for gen­er­al pop­u­la­tion, but rec­om­mend­ed for old­er and high-risk pop­u­la­tions

With just days before President Joe Biden’s Covid-19 booster rollout is set to go into effect, an FDA advisory committee appeared on the verge of not recommending boosters for anyone in the US before a last-minute change of wording laid the groundwork for older adults to have access to a third dose.

The FDA’s adcomm on Vaccines and Related Biological Products (VRBPAC) roundly rejected Pfizer/BioNTech booster shots for all individuals older than 16 by a 16-2 vote Friday afternoon. Soon after, however, the agency posed committee members a new question limiting booster use to the 65-and-older population and individuals at high risk of disease due to occupational exposure or comorbidities.

Lat­est news: It’s a no on uni­ver­sal boost­ers; Pa­tient death stuns gene ther­a­py field; In­side Tril­li­um’s $2.3B turn­around; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Next week is shaping up to be a busy one, as our editor-in-chief John Carroll and managing editor Kyle Blankenship lead back-to-back discussions with a great group of experts to discuss the weekend news and trends. John will be spending 30 minutes with Jake Van Naarden, the CEO of Lilly Oncology, and Kyle has a brilliant panel lined up: Harvard’s Cigall Kadoch, Susan Galbraith, the new head of cancer R&D at AstraZeneca, Roy Baynes at Merck, and James Christensen at Mirati. Don’t miss out on the action — sign up here.

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As­traZeneca, Dai­ichi Sanky­o's ADC En­her­tu blows away Roche's Kad­cy­la in sec­ond-line ad­vanced breast can­cer

AstraZeneca and Japanese drugmaker Daiichi Sankyo think they’ve struck gold with their next-gen ADC drug Enhertu, which has shown some striking data in late-stage breast cancer trials and early solid tumor tests. Getting into earlier patients is now the goal, starting with Enhertu’s complete walkover of a Roche drug in second-line breast cancer revealed Saturday.

Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared with Roche’s ADC Kadcyla in second-line unresectable and/or metastatic HER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo, according to interim data from the Phase III DESTINY-Breast03 head-to-head study presented at this weekend’s #ESMO21.

Merck Research Laboratories CMO Roy Baynes

Mer­ck­'s Keytru­da un­corks full da­ta on lat­est ad­ju­vant win — this time in melanoma — adding bricks to ear­ly can­cer wall

In recent months, the battle for PD-(L)1 dominance has spilled over into early cancer with Merck’s Keytruda and Bristol Myers Squibb’s Opdivo all alone on the front lines. Keytruda now has another shell in its bandolier, and it could spell a quick approval.

Keytruda cut the risk of relapse or death by 35% over placebo (p=0.00658) in high-risk, stage 2 melanoma patients who had previously undergone surgery to remove their tumors, according to full data from the Phase III KEYNOTE-716 presented Saturday at #ESMO21.

Mer­ck flesh­es out Keytru­da win in first-line cer­vi­cal can­cer, adding more fire­pow­er to its ear­ly can­cer push

Merck has worked hard to bring its I/O blockbuster Keytruda into earlier and earlier lines of therapy, and now the wonder drug appears poised to make a quick entry into early advanced cervical cancer.

A combination of Keytruda and chemotherapy with or without Roche’s Avastin cut the risk of death by 33% over chemo with or without Avastin (p=<0.001) in first-line patients with persistent, recurrent or metastatic cervical cancer, according to full data from the Phase III KEYNOTE-826 study presented Saturday at #ESMO21.

Dan O'Day, Gilead CEO (Jim Watson/AFP via Getty Images)

Eu­ro­pean study finds that Gilead­'s Covid-19 an­tivi­ral remde­sivir shows no clin­i­cal ben­e­fit

Gilead’s remdesivir — or Veklury, as it’s marketed in the US — raked in around $2.8 billion last year as the only FDA-approved antiviral to treat Covid-19. But new data from a European study suggest the drug, which has been given to about half of hospitalized Covid patients in the country, has no actual benefit.

The open-label DisCoVeRy trial enrolled Covid-19 patients across 48 sites in Europe to test a handful of treatments, including remdesivir, lopinavir–ritonavir, lopinavir–ritonavir and interferon beta-1a, and hydroxychloroquine. To participate, patients had to show symptoms for seven days and require oxygen support. A total of 429 patients were randomized to receive remdesivir plus standard of care, while 428 were assigned to standard of care alone.

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Covid-19 roundup: FDA re­veals boost­er ad­comm ques­tion; Eli Lil­ly's an­ti­body cock­tail cleared for pre­ven­tion

The FDA released briefing documents this week from the agency and Pfizer each outlining their arguments for today’s Covid-19 booster shot adcomm, but one thing conspicuously missing was the question on which panel members would be voting. But late Thursday night, regulators published that question.

Adcomm members will be asked whether or not the safety and efficacy data from Pfizer/BioNTech’s original Phase III study “support approval” of a booster shot at least six months after the second dose in individuals older than 16. The question notably excludes the real-world data from Israel and other analyses that Pfizer and the Biden administration had said would be a centerpiece of their arguments for boosters.