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.

Like a lot of the majors, Novartis is an open highway for head hunters, or anyone looking to staff a startup. So that was news but not completely unexpected.

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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

The FDA has now spelled out what exactly will be included in the third iteration of Biosimilar User Fee Act (BsUFA) from 2023 through 2027, which similarly to the prescription drug deal, sets fees that industry has to pay for submitting applications, in exchange for firm timelines that the agency must meet.

This latest deal includes several sweeteners for the biosimilar industry, which has yet to make great strides in the US market, with shorter review timelines for safety labeling updates and updates to add or remove an indication that does not contain efficacy data.

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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.

Bennett, who designed and co-developed Luxturna, approved in 2018 for a rare form of blindness, had kept building new gene therapies for eye diseases at her University of Pennsylvania lab. But although the results in animals looked promising, pharma companies and investors kept turning down the pedigreed ophthalmology professor.

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Maureen Hillenmeyer, Hexagon Bio CEO

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

A year after raising a $47 million launch round, the fungi-loving drug hunters at Hexagon Bio have more than doubled their coffers.

Hexagon announced today that it raised another $61 million for its efforts to design cancer and infectious disease drugs based on insights mined from the DNA in millions of species of fungi. The new financing brings Hexagon’s committed funding to over $108 million.

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

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

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