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.
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