EMA and FDA his­tor­i­cal­ly agree on just about every new drug ap­proval, but is that slow­ly chang­ing?

The EMA and FDA con­cur more than 90% of the time in their de­ci­sions to ap­prove new drugs, ac­cord­ing to a new study from EMA and FDA of­fi­cials that looked at 107 ap­pli­ca­tions from 2014 to 2016.

In just eight of the 107 ap­pli­ca­tions, the FDA ini­tial­ly de­clined to ap­prove a new drug or bi­o­log­ic while the EMA ap­proved it, al­though in all eight of those cas­es, the FDA end­ed up ap­prov­ing that drug or bi­o­log­ic. And in one case (Take­da’s Nin­laro (ix­a­zomib) for mul­ti­ple myelo­ma), the FDA ap­proved the treat­ment and the EMA ini­tial­ly did not, but lat­er did.

“Over­all, tak­ing ac­count of the re­sub­mit­ted and re­ex­am­ined ap­pli­ca­tions, the EMA and the FDA had fi­nal dis­cor­dant mar­ket­ing au­tho­riza­tion de­ci­sions for two drugs: cori­fol­litropin al­fa and ataluren,” the study notes, as both were ap­proved by the EMA and not the FDA.

More re­cent­ly, how­ev­er, the EMA’s Com­mit­tee for Med­i­c­i­nal Prod­ucts for Hu­man Use (CHMP) adopt­ed neg­a­tive opin­ions for two drugs in 2018 that were ap­proved by FDA in 2017, and one sick­le cell drug in 2019 that was al­so pre­vi­ous­ly ap­proved by FDA. In ad­di­tion, CHMP raised ques­tions about Mit­subishi Tan­abe Phar­ma’s treat­ment for amy­otroph­ic lat­er­al scle­ro­sis, which with­drew its ap­pli­ca­tion this year, and which was ap­proved by FDA in 2017.

“Di­ver­gence in ap­proval de­ci­sions, type of ap­proval, and ap­proved in­di­ca­tion were pri­mar­i­ly due to dif­fer­ences in agen­cies’ con­clu­sions about ef­fi­ca­cy based on re­view of the same da­ta or dif­fer­ing clin­i­cal da­ta sub­mit­ted to sup­port the ap­pli­ca­tion,” the study pub­lished in Clin­i­cal Phar­ma­col­o­gy & Ther­a­peu­tics found.

In the more re­cent case of the sick­le cell drug, the FDA said its ap­proval was based on a tri­al show­ing that pa­tients treat­ed with En­dari (glu­t­a­mine) ex­pe­ri­enced few­er hos­pi­tal vis­its for sick­le cell crises, on av­er­age, when com­pared to place­bo. But the EMA’s CHMP said it “con­sid­ered that the main study did not show that [glu­t­a­mine] was ef­fec­tive at re­duc­ing the num­ber of sick­le cell crises or hos­pi­tal vis­its.”

The study al­so notes how the FDA more com­mon­ly grant­ed ac­cel­er­at­ed ap­provals (12/25 in on­col­o­gy and 5/8 in hema­tol­ogy) than the EMA grant­ed con­di­tion­al mar­ket­ing au­tho­riza­tion or au­tho­riza­tion un­der ex­cep­tion­al cir­cum­stances (7/25 in on­col­o­gy and 2/8 in hema­tol­ogy).

But sub­mis­sions in these ar­eas of­ten oc­curred lat­er to the EMA than the FDA, and of­ten in­clud­ed ad­di­tion­al clin­i­cal tri­als or more ma­ture da­ta from the same clin­i­cal tri­al than were sub­mit­ted to the FDA. “In those in­stances, the EMA was more like­ly than the FDA to grant stan­dard ap­proval (where­as the FDA is­sued ac­cel­er­at­ed ap­proval) or a broad­er in­di­ca­tion,” the study said.

The study al­so found the EMA had a high­er rate of first-cy­cle ap­provals than the FDA, and the re­searchers “ob­served re­mark­able sim­i­lar­i­ty in the ba­sic sci­en­tif­ic and da­ta in­ter­pre­ta­tion is­sues raised by the FDA and the EMA dur­ing re­views of the same ap­pli­ca­tions. Specif­i­cal­ly, most of the FDA’s sec­ond cy­cle ap­provals (i.e., ap­provals af­ter re­sub­mis­sion of the ap­pli­ca­tions) were based on sub­mis­sion by the spon­sor of the same ad­di­tion­al da­ta that EMA had re­ceived dur­ing its ini­tial re­view ei­ther from the start or fol­low­ing re­quest af­ter clock‐stops.”

In their dis­cus­sion of the re­sults, the study au­thors al­so note the study’s lim­i­ta­tions, such as on­ly us­ing two years’ worth of da­ta. But over­all, the two agen­cies are com­mu­ni­cat­ing and work­ing to­geth­er more close­ly than in years past.

“The high rate of con­ver­gence in the au­tho­ri­sa­tion of new med­i­cines at EMA and the FDA is the re­sult of ex­pand­ed in­vest­ment in di­a­logue and co­op­er­a­tion since 2003 and has fos­tered align­ment be­tween the EU and the US with re­spect to de­ci­sions on mar­ket­ing au­tho­ri­sa­tions, while both agen­cies eval­u­ate ap­pli­ca­tions in­de­pen­dent­ly of each oth­er,” said Zaide Frias, head of the EMA’s hu­man med­i­cines eval­u­a­tion di­vi­sion.

So­cial im­age: Shut­ter­stock, AP


RAPS: First pub­lished in Reg­u­la­to­ry Fo­cus™ by the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety, the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care prod­ucts. Click here for more in­for­ma­tion.

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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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.

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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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.

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.

Skin tu­mors in mice force Pro­tag­o­nist to halt lead pro­gram, crush­ing stock

Protagonist Therapeutics just can’t catch a break.

Six months after the Newark, CA-based biotech unveiled grand plans to launch its lead candidate for blood disorders into a Phase III trial, the FDA has slapped the program with a clinical hold. The halt — which applies to all trials involving the candidate, rusfertide — comes after skin tumors were discovered in mice treated with the drug, according to Protagonist.

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Take­da scores a win for a rare type of lung can­cer, gear­ing up for a show­down with J&J

Four months after J&J’s infused drug Rybrevant scored the industry’s first win in a rare type of non-small cell lung cancer (NSCLC), Takeda is following up with an oral option for the small but desperate patient population.

The FDA granted an accelerated approval to Takeda’s oral TKI inhibitor Exkivity (mobocertinib) in metastatic NSCLC patients with EGFR exon 20 gene mutations who had previously undergone platinum-based chemotherapy, the company announced on Wednesday.

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