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.

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

President Donald Trump (left) and Moncef Slaoui, head of Operation Warp Speed (Alex Brandon, AP Images)

White House names fi­nal­ists for Op­er­a­tion Warp Speed — with 5 ex­pect­ed names and one no­table omis­sion

A month after word first broke of the Trump Administration’s plan to rapidly accelerate the development and production of a Covid-19 vaccine, the White House has selected the five vaccine candidates they consider most likely to succeed, The New York Times reported.

Most of the names in the plan, known as Operation Warp Speed, will come as little surprise to those who have watched the last four months of vaccine developments: Moderna, which was the first vaccine to reach humans and is now the furthest along of any US effort; J&J, which has not gone into trials but received around $500 million in funding from BARDA earlier this year; the joint AstraZeneca-Oxford venture which was granted $1.2 billion from BARDA two weeks ago; Pfizer, which has been working with the mRNA biotech BioNTech; and Merck, which just entered the race and expects to put their two vaccine candidates into humans later this year.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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UP­DAT­ED: Es­ti­mat­ing a US price tag of $5K per course, remde­sivir is set to make bil­lions for Gilead, says key an­a­lyst

Data on remdesivir — the first drug shown to benefit Covid-19 patients in a randomized, controlled trial setting — may be murky, but its maker Gilead could reap billions from the sales of the failed Ebola therapy, according to an estimate by a prominent Wall Street analyst. However, the forecast, which is based on a $5,000-per-course US price tag, triggered the ire of one top drug price expert.

A low-pro­file biotech bests Re­gen­eron in high-pro­file patent suit

For nearly a decade now, the low-profile Cambridge biotech Kymab has been battling in US, UK, Japanese and Australian courts with the biotech behemoth Regeneron.

Regeneron has turned itself into a $70 billion company off of a platform of transgenically humanized mice they can use to make antibodies for anything from Ebola to colorectal cancer. The technology took decades and billions to build, 20 years from the company’s founding to the first approved drug. And the company guards and touts it zealously, breaking their production process down into various branded components — Velocimmune, Velocigene, Velocimouse and four other Velocis — and sometimes suing would-be copycats. In 2014, most notably, they sued two Pfizer-backed entities for patent infringement.

Credit: AP Images

Covid-19 roundup: BAR­DA sup­ports Op­er­a­tion Warp Speed with big $628M con­tract to ser­vice Amer­i­ca's vac­cine pro­duc­tion needs

Another BARDA contract designed to service America’s Covid-19 vaccine needs has been deployed.

The White House-led initiative designed to bankroll development to bring a vaccine to the American public by this fall — Operation Warp Speed — has via BARDA handed a meaty contract to the maker of an FDA-licensed anthrax vaccine to open up its manufacturing apparatus to shore up production of Covid-19 vaccines.

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FDA de­lays de­ci­sion on No­var­tis’ po­ten­tial block­buster MS drug, wip­ing away pri­or­i­ty re­view

So much for a speedy review.

In February, Novartis announced that an application for their much-touted multiple sclerosis drug ofatumumab had been accepted and, with the drug company cashing in on one of their priority review vouchers, the agency was due for a decision by June.

But with June less than 48 hours old, Novartis announced the agency has extended their review, pushing back the timeline for approval or rejection to September. The Swiss pharma filed the application in December, meaning their new schedule will be nearly in line with the standard 10-month window period had they not used the priority voucher.

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Bull­ish biotech mar­ket pro­pels Pli­ant to $144M IPO — as No­var­tis pro­vides a $10M boost

After pharma partner Novartis boosted its IPO with a $10 million private placement, Pliant Therapeutics has wrapped its journey to the Nasdaq on a high note.

Pliant had penciled in a $86 million raise back in May. But as has become the norm in recent months, that initial number has turned out to be a mere placeholder, making way for the final haul of $144 million.

The South San Francisco biotech did so by pricing at $16, the high end of the range, while bringing the number of shares offered up to 9 million.