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.

Author

Zachary Brennan

managing editor, RAPS

A New Fron­tier: The In­ner Ear

What happens when a successful biotech venture capitalist is unexpectedly diagnosed with a chronic, life-disrupting vertigo disorder? Innovation in neurotology.

That venture capitalist was Jay Lichter, Ph.D., and after learning there was no FDA-approved drug treatment for his condition, Ménière’s disease, he decided to create a company to bring drug development to neurotology. Otonomy was founded in 2008 and is dedicated to finding new drug treatments for the hugely underserved community living with balance and hearing disorders. Helping patients like Jay has been the driving force behind Otonomy, a company heading into a transformative 2020 with three clinical trial readouts: Phase 3 in Ménière’s disease, Phase 2 in tinnitus, and Phase 1/2 in hearing loss. These catalysts, together with others in the field, highlight the emerging opportunity in neurotology.
Otonomy is leading the way in neurotology
Neurotology, or the treatment of inner ear neurological disorders, is a large and untapped market for drug developers: one in eight individuals in the U.S. have moderate-to-severe hearing loss, tinnitus or vertigo disorders such as Ménière’s disease.1 With no FDA-approved drug treatments available for these conditions, the burden on patients—including social anxiety, lower quality of life, reduced work productivity, and higher rates of depression—can be significant.2, 3, 4

Joe Jimenez, Getty

Ex-No­var­tis CEO Joe Jimenez is tak­ing an­oth­er crack at open­ing a new chap­ter in his ca­reer — and that in­cludes a new board seat and a $250M start­up

Joe Jimenez is back.

The ex-CEO of Novartis has taken a board seat on Century Therapeutics, the Versant and Bayer-backed startup focused on coming up with a brand new twist on cell therapies for cancer — a field where Jimenez made his mark backing the first personalized CAR-T approved for use.

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Credit: Shutterstock

Can we make the an­tibi­ot­ic mar­ket great again?

The standard for-profit model in drug development is straightforward. Spend millions, even billions, to develop a medicine from scratch. The return on investment (and ideally a tidy profit) comes via volume and/or price, depending on the disease. But the string of big pharma exits and slew of biotech bankruptcies indicate that the model is sorely flawed when it comes to antibiotics.

The industry players contributing to the arsenal of antimicrobials are fast dwindling, and the pipeline for new antibiotics is embarrassingly sparse, the WHO has warned. Drugmakers are enticed by greener pastures, compared to the long, arduous and expensive path to antibiotic approval that offers little financial gain as treatments are typically priced cheaply, and often lose potency over time as microbes grow resistant to them.

Top Har­vard chemist caught up in FBI’s 'T­hou­sand Tal­ents' drag­net, ac­cused of ly­ing about Chi­nese con­nec­tions, pay

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The agency accused Charles M. Lieber, who chairs the university’s chemistry and chemical biology department, with lying about his involvement in China’s Thousand Talents campaign, which was established as a way of drawing in innovators from around the world. And the scientist, 60, was charged with making false statements about his ties to China.

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Eye­ing a trio of tri­al ini­ti­a­tions, Jim Wilson's gene ther­a­py start­up woos Bruce Gold­smith from Deer­field as CEO

Passage Bio — Jim Wilson’s self-described “legacy company” — has wooed a seasoned biotech executive to steer the clinical entry of its first three gene therapy programs.

Bruce Goldsmith jumps to the helm of Passage after a brief CEO stint at Civetta, a cancer-focused startup he helped launch while a venture partner at Deerfield. He takes over from OrbiMed partner and interim chief Stephen Squinto, who will now lead the R&D team.

The FTC and New York state ac­cuse Mar­tin Shkre­li of run­ning a drug mo­nop­oly. They plan to squash it — and per­ma­nent­ly ex­ile him

Pharma bro Martin Shkreli was jailed, publicly pilloried and forced to confront some lawmakers in Washington riled by his move to take an old generic and move the price from $17.50 per pill to $750. But through 4 years of controversy and public revulsion, his company never backed away from the price — left uncontrolled by a laissez faire federal policy on a drug’s cost.

Now the FTC and the state of New York plan to pry his fingers off the drug once and for all and open it up to some cheap competition. And their lawsuit is asking that Shkreli — with several years left on his prison sentence — be banned permanently from the pharma industry.

UP­DAT­ED: Ac­celeron res­ur­rects block­buster hopes for so­tater­cept with pos­i­tive PhII — and shares rock­et up

Acceleron $XLRN says that its first major trial readout of 2020 is a success.

In a Phase II study of 106 patients with pulmonary arterial hypertension (PAH), Acceleron’s experimental drug sotatercept hit its primary endpoint: a significant reduction in pulmonary vascular resistance. The drug also met three different secondary endpoints, including the 6-minute walking test.

“We’re thrilled to report such positive topline results from the PULSAR trial,” Acceleron CEO Habib Dable said in a statement. The company said in a conference call they plan on discussing a Phase III trial design with regulators.

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Short at­tack­er Sahm Ad­ran­gi draws crosshairs over a fa­vorite of Sanofi’s new CEO — with PhII da­ta loom­ing

Sahm Adrang Kerrisdale

Kerrisdale chief Sahm Adrangi took a lengthy break from his series of biotech short attacks after his chief analyst in the field pulled up stakes and went solo. But he’s making a return to drug development this morning, drawing crosshairs over a company that’s one of new Sanofi CEO Paul Hudson’s favorite collaborators.

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Amber Saltzman (Ohana)

Flag­ship's first ven­ture of 2020 is out, and it's all about sperm

A couple years ago, Amber Salzman got a call as she was returning East full-time after a two-year stint running a gene therapy company in California.

It was from someone at Flagship Pioneering, the deep-pocketed biotech venture firm. They had a new company with a new way of thinking about sperm. It had been incubating for over a year, and now they wanted her to run it.

“It exactly fit,” Salzman told Endpoints News. “I just thought I had to do something.”