EMA coun­ters the aca­d­e­mics who crit­i­cized the can­cer drug ap­proval process

As more can­cer drugs are ap­proved and prices con­tin­ue to rise, ques­tions have cir­cu­lat­ed on whether these drugs are ex­tend­ing pa­tient sur­vival or im­prov­ing qual­i­ty of life. A re­search ar­ti­cle pub­lished in the BMJ last week re­viewed the ap­proval of drugs by the EMA from 2009 to 2013 and not­ed that most drugs en­tered the mar­ket with­out ev­i­dence of sur­vival ben­e­fits or QoL. But rather than re­fute the BMJ ar­ti­cle’s find­ings in a re­sponse pub­lished Thurs­day, Francesco Pig­nat­ti, head of on­col­o­gy, hema­tol­ogy and di­ag­nos­tics at the EMA, wrote that the ar­ti­cle’s find­ings “are not sur­pris­ing to any­one fa­mil­iar with can­cer drug de­vel­op­ment.”

Vinay Prasad

The BMJ re­search is part of a large and grow­ing num­ber of ques­tions cir­cu­lat­ing on gains made with re­cent can­cer drug ap­provals. “When there were sur­vival gains over ex­ist­ing treat­ment op­tions or place­bo, they were of­ten mar­gin­al,” the UK and Lat­vian pro­fes­sors who con­duct­ed the re­search not­ed in its con­clu­sion.

Vinay Prasad, as­sis­tant pro­fes­sor of med­i­cine at Ore­gon Health and Sci­ence Uni­ver­si­ty, has been a vo­cal crit­ic of the wave of re­cent ap­provals and wrote the ac­com­pa­ny­ing ed­i­to­r­i­al to the BMJ ar­ti­cle, in which he called the reg­u­la­to­ry sys­tem “bro­ken.” He’s pre­vi­ous­ly writ­ten in Fo­cus on how most can­cer drugs “cost too much and give us too lit­tle” in re­sponse to an op-ed in Fo­cus on a JA­MA study he co-au­thored.

Back in June, Richard Paz­dur, FDA’s di­rec­tor of the On­col­o­gy Cen­ter of Ex­cel­lence, al­so dis­cussed in a blog post how to mea­sure pa­tient ben­e­fit with can­cer treat­ment.

EMA Re­sponse

Francesco Pig­nat­ti

Pig­nat­ti of­fered four rea­sons why in many sit­u­a­tions “demon­strat­ing a clear ef­fect on sur­vival or QoL is not fea­si­ble and a ben­e­fit can be shown on the ba­sis of oth­er end­points”:

  1. Over­all sur­vival may be dif­fi­cult to de­tect be­cause con­trol-group pa­tients in a ran­dom­ized clin­i­cal tri­al “switch to the ex­per­i­men­tal treat­ment af­ter pro­gres­sion, or mul­ti­ple sub­se­quent lines of ef­fec­tive treat­ments ‘di­lute’ the ef­fect of a drug used in ear­li­er lines.” In such cas­es, EMA says, pro­gres­sion-free sur­vival (de­fined as “the time dur­ing which treat­ment can in­duce and main­tain a re­sponse or at least de­lay the growth of can­cer”) has been the ef­fi­ca­cy out­come used for ap­proval.
  2. When tu­mor shrink­age and re­sponse du­ra­tion are ob­served on the ba­sis of a sin­gle-arm tri­al in a well-de­fined pop­u­la­tion with high un­met need, RCTs can be con­sid­ered un­eth­i­cal or in­fea­si­ble, and ear­ly ap­proval mech­a­nisms are used. Though he cau­tions that this “ap­plies to a mi­nor­i­ty of cas­es and re­quires that the course of the dis­ease is high­ly pre­dictable, that there are no good ther­a­peu­tic al­ter­na­tives and that there are suf­fi­cient sup­port­ive clin­i­cal and non-clin­i­cal da­ta to show a pos­i­tive ben­e­fit-risk bal­ance.”
  3. In terms of QoL, he notes that this “is rarely used as the pri­ma­ry ef­fi­ca­cy end­point in can­cer clin­i­cal tri­als and con­vinc­ing clin­i­cal ben­e­fits in terms of QoL are on­ly rarely shown. This, how­ev­er, does not mean that EMA does not val­ue such stud­ies, which are en­cour­aged even if of­ten they do not lead to ro­bust con­clu­sions.”
  4. And fi­nal­ly, he notes that “gi­ant leaps” in ben­e­fits are “rel­a­tive­ly rare” and the Eu­ro­pean So­ci­ety for Med­ical On­col­o­gy Mag­ni­tude of Clin­i­cal Ben­e­fit Scale used by the re­searchers in the BMJ ar­ti­cle “was nev­er de­signed for the pur­pose of clin­i­cal de­ci­sion-mak­ing and was main­ly con­struct­ed on the ba­sis of on­col­o­gists’ views rather than a sys­tem­at­ic eval­u­a­tion of pa­tient pref­er­ences.”

Pig­nat­ti adds that con­duct­ing tri­als “ac­cord­ing to the most rig­or­ous method­ol­o­gy is strong­ly en­cour­aged” but is not “a pre-req­ui­site for ap­proval pro­vid­ed that ex­ist­ing un­cer­tain­ties can be ad­dressed on the ba­sis of the to­tal­i­ty of the da­ta, in­clud­ing fu­ture stud­ies, where ap­pro­pri­ate … re­strict­ing ap­provals of can­cer drugs on­ly to sit­u­a­tions where there is in­dis­putable ev­i­dence of im­prove­ment in sur­vival or QoL will not im­prove the lives of can­cer pa­tients.”


First pub­lished here. Reg­u­la­to­ry Fo­cus is the flag­ship on­line pub­li­ca­tion of the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety (RAPS), the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care and re­lat­ed prod­ucts, in­clud­ing med­ical de­vices, phar­ma­ceu­ti­cals, bi­o­log­ics and nu­tri­tion­al prod­ucts. Email news@raps.org for more in­for­ma­tion.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

The End­points 11: They've got mad mon­ey and huge am­bi­tions. It's time to go big or go home

These days, selecting a group of private biotechs for the Endpoints 11 spotlight begins with a sprint to get ahead of IPOs and the M&A teams at Big Pharma. I’ve had a couple of faceplants earlier this year, watching some of the biotechs on my short list choose a quick leap onto Nasdaq or into the arms of a buyer.

Vividion, you would have been a great pick for the Endpoints 11. I’m sorry I missed you.

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Dave Lennon, former president of Novartis Gene Therapies

So what hap­pened with No­var­tis Gene Ther­a­pies? Here's your an­swer

Over the last couple of days it’s become clear that the gene therapy division at Novartis has quietly undergone a major reorganization. We learned on Monday that Dave Lennon, who had pursued a high-profile role as president of the unit with 1,500 people, had left the pharma giant to take over as CEO of a startup.

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Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

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Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

FDA+ roundup: Bs­U­FA III ready for show­time, court tells FDA to re-work com­pound­ing plan, new guid­ance up­dates and more

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Jean Bennett (Brent N. Clarke/Invision/AP Images)

Lux­tur­na in­ven­tor Jean Ben­nett starts a new gene ther­a­py com­pa­ny to tack­le rare dis­eases left be­hind by phar­ma, VCs

A few years ago Jean Bennett found herself in a surprising place for a woman who invented the first gene therapy ever approved in the United States: No one, it seemed, wanted her work.

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Maureen Hillenmeyer, Hexagon Bio CEO

Hexa­gon Bio rais­es $61M to con­tin­ue ef­forts to turn fun­gi in­to drugs

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David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

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