Covid-19 roundup: EMA of­fi­cial says 'clear' link be­tween As­traZeneca shot and blood clots — re­port; No­vavax al­lows place­bo group to get vac­cine

For the first time Tues­day, health of­fi­cials ac­knowl­edged a link be­tween the As­traZeneca/Ox­ford Uni­ver­si­ty Covid-19 vac­cine and blood clots fol­low­ing a tense few weeks of coun­tries across Eu­rope sus­pend­ing use of the shot.

A top vac­cine ex­pert at the EMA said in an in­ter­view with Ital­ian news­pa­per Il Mes­sag­gero that there is a con­nec­tion be­tween the vac­cines and throm­bot­ic events, but the caus­es re­main un­known. The in­di­vid­ual ap­peared to dis­close the in­for­ma­tion sep­a­rate­ly from an of­fi­cial EMA an­nounce­ment but not­ed that the agency would do so lat­er Tues­day and pro­vide up­dat­ed guide­lines on the shot Wednes­day, ac­cord­ing to The Guardian.

“In my opin­ion we can now say it, it is clear that there is an as­so­ci­a­tion with the vac­cine. How­ev­er, we still do not know what caus­es this re­ac­tion,” EMA head of vac­cines Mar­co Cav­a­leri told the pa­per.

Cav­a­leri no­tably did not pro­vide any ev­i­dence to back up his claims. As­traZeneca did not im­me­di­ate­ly re­spond to an End­points News re­quest for com­ment.

Re­ports of the blood clots first popped up in ear­ly March af­ter a 49-year-old woman in Aus­tria died from “se­vere co­ag­u­la­tion dis­or­ders” af­ter re­ceiv­ing the shot. Soon af­ter, sev­er­al EU mem­ber states be­gan sus­pend­ing use of the shot while stud­ies in­to the blood clots be­gan. The EMA is still look­ing in­to 14 deaths among in­di­vid­u­als who had re­ceived the shot by March 22.

In a cul­mi­na­tion of the sus­pen­sions, Ger­many, the de fac­to leader of the EU, halt­ed vac­cine ad­min­is­tra­tion for its un­der-60 pop­u­la­tion just last week.

As­traZeneca has main­tained that the shots are safe, and re­ceived back­ing from the EMA and the World Health Or­ga­ni­za­tion, who both said the ben­e­fits of tak­ing the shot out­weigh the risks. Dur­ing a press con­fer­ence last week with the EMA safe­ty com­mit­tee, known as PRAC, the agency re­port­ed that though the blood clot cas­es are rare, they ap­pear to be oc­cur­ring more fre­quent­ly in young and mid­dle-aged women than oth­er groups.

The to­tal cas­es showed that about 1 in 100,000 in­di­vid­u­als who re­ceived the As­traZeneca shot are see­ing these rare and se­vere events in Eu­rope, the EMA said. An an­nounce­ment pro­vid­ing up­dates of the PRAC stud­ies was ex­pect­ed this week.

Tues­day’s com­ments come as Eu­ro­pean coun­tries con­tin­ue to block ex­ports of the shots from leav­ing their shores. The EU has blocked about 3.1 mil­lion vac­cines head­ed for Aus­tralia so far, Reuters re­port­ed.

No­vavax al­lows place­bo group to re­ceive vac­cines

No­vavax has up­dat­ed its vac­cine tri­al pro­to­col to al­low pa­tients in the place­bo arm to re­ceive the shot, the com­pa­ny an­nounced Mon­day.

The crossover al­lows for those in No­vavax’s UK and US/Mex­i­co Phase III stud­ies to re­ceive an ad­di­tion­al round of in­jec­tions while re­main­ing blind­ed. In­di­vid­u­als who re­ceived the vac­cine in the ini­tial round will get the place­bo, and vice ver­sa.

In the com­pa­ny’s South Africa Phase IIb study, vol­un­teers who re­ceived the place­bo will al­so get the vac­cine, while those who re­ceived the vac­cine will get a boost­er shot. Par­tic­i­pants from all three arms will con­tin­ue to be fol­lowed for up to two years.

“The crossover arms en­sure that all par­tic­i­pants have ac­cess to an ac­tive vac­cine can­di­date while al­low­ing No­vavax to con­tin­ue to mon­i­tor the safe­ty and ef­fi­ca­cy of our vac­cine over the long term,” CMO Fil­ip Dubovsky said in a state­ment.

Last month, No­vavax’s UK tri­al showed a fi­nal ef­fi­ca­cy of 96% in the arm against mild, mod­er­ate and se­vere Covid-19 cas­es in the UK. But that num­ber fell pre­cip­i­tous­ly in the South Africa arm, where it reg­is­tered on­ly 50% ef­fi­ca­cy.

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.