Emer Cooke, EMA executive director (Martial Trazzini/Shutterstock)

Rare blood clot events more com­mon among women re­ceiv­ing As­traZeneca Covid-19 vac­cine, EMA says

The EMA is stick­ing with its state­ment that As­traZeneca’s Covid-19 vac­cine is safe and ef­fec­tive, but the agency al­so dis­cussed new da­ta show­ing that younger women are more fre­quent­ly see­ing these very rare cas­es of some­times fa­tal blood clots when com­pared with the gen­er­al pop­u­la­tion, al­though more women al­so re­ceived the vac­cine than men.

EMA ex­ec­u­tive di­rec­tor Emer Cooke said Wednes­day at a press con­fer­ence that the agency’s safe­ty com­mit­tee is still re­view­ing the rare events, known as cere­bral ve­nous si­nus throm­bo­sis (CVST), which as of March 22, to­tal 62 out of 9.2 mil­lion As­traZeneca vac­ci­na­tions across the Eu­ro­pean Eco­nom­ic Area (EEA). Four­teen of those 62 cas­es were fa­tal, and 44 oc­curred in the EEA, she not­ed.

The to­tal cas­es show that about 1 in 100,000 re­ceiv­ing the As­traZeneca vac­cine are see­ing these rare and se­vere events in Eu­rope, al­though a causal or as­so­cia­tive link be­tween the vac­cine and the events has not been es­tab­lished, ac­cord­ing to Pe­ter Ar­lett, head of the phar­ma­covig­i­lance and epi­demi­ol­o­gy de­part­ment at the EMA.

The num­ber of rare events for the As­traZeneca vac­cine al­so com­pares with less than 1 in 1 mil­lion for the Pfiz­er and Mod­er­na vac­cines each. But Cooke stressed that dif­fer­ent groups and num­bers of peo­ple have re­ceived each of the vac­cines so it’s dif­fi­cult to com­pare them.

The EMA’s safe­ty com­mit­tee, known as PRAC, will con­tin­ue to re­view the da­ta as it comes in on a dai­ly ba­sis and make an­oth­er an­nounce­ment on the As­traZeneca vac­cine next week, Cooke not­ed, ex­plain­ing that the EMA’s con­clu­sion two weeks ago has not changed and the ben­e­fits of the As­traZeneca vac­cine still out­weigh the risks.

But cas­es of CVST are oc­cur­ring at a high­er rate among those un­der the age of 60 and re­ceiv­ing the As­traZeneca vac­cine. Ar­lett added, “If we look at in­di­vid­u­als un­der 60, then we do see more cas­es of cere­bral ve­nous si­nus throm­bo­sis than we would ex­pect to see from the back­ground.”

Cooke al­so not­ed a high­er in­ci­dence among women be­tween the ages of 30 and 45, when com­pared to the gen­er­al pop­u­la­tion. CVST is more com­mon in women in gen­er­al, but about two-thirds of those re­ceiv­ing the As­traZeneca vac­cine in Eu­rope were women, Ar­lett added.

An As­traZeneca spokesper­son told End­points News via email: “While the EMA re­port­ed that the PRAC’s in­ves­ti­ga­tion did show some pre­dom­i­nance of cas­es in cer­tain groups in­clud­ing younger women they said it is pre­ma­ture to draw any con­clu­sions on that point right now. PRAC is cur­rent­ly as­sess­ing many pos­si­bil­i­ties in­clud­ing that the high­er pro­por­tion of cas­es seen in young women may be due to a high­er pro­por­tion of women vac­ci­nat­ed or a high­er risk of throm­bot­ic events in this pop­u­la­tion.”

The up­date from the EMA comes as Ger­many said it will stop us­ing As­traZeneca’s vac­cine on res­i­dents younger than 60. Sev­er­al jour­nal­ists ques­tioned the EMA on the to­tal of 62 CVST cas­es, not­ing that Ger­many alone has re­port­ed 31 cas­es, but Cooke said the 62 events do not ac­count for all of the Ger­man cas­es and the EMA’s safe­ty com­mit­tee will look at new­er fig­ures be­fore mak­ing its an­nounce­ment next week.

Cana­da al­so re­cent­ly said it would halt As­traZeneca shots for peo­ple 55 and younger, while Swe­den and Fin­land are on­ly us­ing the vac­cine for those over 65.

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.