Cas­cade of costs could push CAR-T ther­a­py to $1.5M per pa­tient

Dr. Kei­th Eaton, who suf­fered from leukemia, pos­es for a pho­to with his par­ents fol­low­ing his bone mar­row trans­plant. He says he ran up med­ical bills of $500,000 when he par­tic­i­pat­ed in a clin­i­cal tri­al of CAR T cells in 2013. (Cour­tesy of Dr. Kei­th Eaton)

Out­rage over the high cost of can­cer care has fo­cused on sky­rock­et­ing drug prices, in­clud­ing the $475,000 price tag for the coun­try’s first gene ther­a­py, No­var­tis’ Kym­ri­ah, a leukemia treat­ment ap­proved in Au­gust.

But the to­tal costs of Kym­ri­ah and the 21 sim­i­lar drugs in de­vel­op­ment — known as CAR T-cell ther­a­pies — will be far high­er than many have imag­ined, reach­ing $1 mil­lion or more per pa­tient, ac­cord­ing to lead­ing can­cer ex­perts. The next CAR T-cell drug could be ap­proved as soon as No­vem­ber.

Al­though Kym­ri­ah’s price tag has “shat­tered on­col­o­gy drug pric­ing norms,” said Leonard Saltz, chief of gas­troin­testi­nal on­col­o­gy at Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter in New York, “the stick­er price is just the start­ing point.”

These ther­a­pies lead to a cas­cade of costs, pro­pelled by se­ri­ous side ef­fects that re­quire so­phis­ti­cat­ed man­age­ment, Saltz said. For this class of drugs, Saltz ad­vised con­sumers to “think of the $475,000 as parts, not la­bor.”

Dr. Hagop Kan­tar­jian, a leukemia spe­cial­ist and pro­fes­sor at the Uni­ver­si­ty of Texas MD An­der­son Can­cer Cen­ter, es­ti­mates Kym­ri­ah’s to­tal cost could reach $1.5 mil­lion.

CAR T-cell ther­a­py is ex­pen­sive be­cause of the unique way that it works. Doc­tors har­vest pa­tients’ im­mune cells, ge­net­i­cal­ly al­ter them to rev up their abil­i­ty to fight can­cer, then re­in­fuse them in­to pa­tients.

Tak­ing the brakes off the im­mune sys­tem, Kan­tar­jian said, can lead to life-threat­en­ing com­pli­ca­tions that re­quire lengthy hos­pi­tal­iza­tions and ex­pen­sive med­ica­tions, which are pre­scribed in ad­di­tion to con­ven­tion­al can­cer ther­a­py, rather than in place of it.

Dr. Kei­th Eaton, like near­ly half of pa­tients who re­ceive CAR T-cell ther­a­py, de­vel­oped a life-threat­en­ing com­pli­ca­tion in which his im­mune sys­tem over­re­act­ed. He says he feels for­tu­nate to be healthy to­day.

Dr. Kei­th Eaton, a Seat­tle on­col­o­gist, said he ran up med­ical bills of $500,000 when he par­tic­i­pat­ed in a clin­i­cal tri­al of CAR T cells in 2013, even though all pa­tients in the study re­ceived the med­ica­tion for free. Eaton, who suf­fered from leukemia, spent near­ly two months in the hos­pi­tal.

Kei­th Eaton 

Like Eaton, near­ly half of pa­tients who re­ceive CAR T cells de­vel­op a se­vere or life-threat­en­ing com­pli­ca­tion called “cy­tokine storm,” in which the im­mune sys­tem over­re­acts, caus­ing dan­ger­ous­ly high fevers and sud­den drops in blood pres­sure. These pa­tients are typ­i­cal­ly treat­ed in the in­ten­sive care unit. Oth­er se­ri­ous side ef­fects in­clude stroke-like symp­toms and co­ma.

The cy­tokine storm felt like “the worst flu of your life,” said Eaton, now 51. His fever spiked so high that a hos­pi­tal nurse as­sumed the ther­mome­ter was bro­ken. Eaton replied, “It’s not bro­ken. My tem­per­a­ture is too high to reg­is­ter on the ther­mome­ter.”

Al­though Eaton re­cov­ered, he wasn’t done with treat­ment. His doc­tors rec­om­mend­ed a bone-mar­row trans­plant, an­oth­er har­row­ing pro­ce­dure, at a cost of hun­dreds of thou­sands of dol­lars.

Eaton said he feels for­tu­nate to be healthy to­day, with tests show­ing no ev­i­dence of leukemia. His in­sur­er paid for al­most every­thing.

Kym­ri­ah’s stick­er price is es­pe­cial­ly “out­ra­geous” giv­en its rel­a­tive­ly low man­u­fac­tur­ing costs, said Dr. Walid Gel­lad, co-di­rec­tor of the Cen­ter for Phar­ma­ceu­ti­cal Pol­i­cy and Pre­scrib­ing at the Uni­ver­si­ty of Pitts­burgh.

The gene ther­a­py process used to cre­ate Kym­ri­ah costs about $15,000, ac­cord­ing to a 2012 pre­sen­ta­tion by Dr. Carl June, who pi­o­neered CAR T-cell re­search at the Uni­ver­si­ty of Penn­syl­va­nia. June could not be reached for com­ment.

To quell un­rest about price, No­var­tis has of­fered pa­tients and in­sur­ers a new twist on the mon­ey-back guar­an­tee.

No­var­tis will charge for the drug on­ly if pa­tients go in­to re­mis­sion with­in one month of treat­ment. In a key clin­i­cal tri­al, 83 per­cent of the chil­dren and young adults treat­ed with Kym­ri­ah went in­to re­mis­sion with­in three months. No­var­tis calls the plan “out­comes-based pric­ing.”

No­var­tis is “work­ing through the spe­cif­ic de­tails” of how the pric­ing plan will af­fect the Cen­ters for Medicare & Med­ic­aid Ser­vices, which pays for care for many can­cer pa­tients, com­pa­ny spokes­woman Julie Ma­sow said. “There are many hur­dles” to this type of pric­ing plan but, Ma­sow said, “No­var­tis is com­mit­ted to mak­ing this hap­pen.”

Ma­sow said that Kym­ri­ah’s man­u­fac­tur­ing costs are much high­er than $15,000, al­though she didn’t cite a spe­cif­ic dol­lar amount. She not­ed that No­var­tis has in­vest­ed heav­i­ly in the tech­nol­o­gy, de­sign­ing “an in­no­v­a­tive man­u­fac­tur­ing fa­cil­i­ty and process specif­i­cal­ly for cel­lu­lar ther­a­pies.”

As for Kym­ri­ah-re­lat­ed hos­pi­tal and med­ica­tion charges, “costs will vary from pa­tient to pa­tient and treat­ment cen­ter to treat­ment cen­ter, based on the lev­el of care each pa­tient re­quires,” Ma­sow said. “Kym­ri­ah is a one-time treat­ment that has shown re­mark­able ear­ly, deep and durable re­spons­es in these chil­dren who are very sick and of­ten out of op­tions.”

Some doc­tors said Kym­ri­ah, which could be used by about 600 pa­tients a year, of­fers an in­cal­cu­la­ble ben­e­fit for des­per­ate­ly ill young peo­ple. Kym­ri­ah is ap­proved for chil­dren and young adults with a type of acute lym­phoblas­tic leukemia and al­ready have been treat­ed with at least two oth­er can­cer ther­a­pies.

“A kid’s life is price­less,” said Dr. Michelle Her­mis­ton, di­rec­tor of pe­di­atric im­munother­a­py at UCSF Be­nioff Chil­dren’s Hos­pi­tal San Fran­cis­co. “Any giv­en kid has the po­ten­tial to make fi­nan­cial im­pacts over a life­time that far out­weigh the cost of their cure. From this per­spec­tive, every child in my mind de­serves the best cu­ra­tive ther­a­py we can of­fer.”

Oth­er can­cer doc­tors say the No­var­tis plan is no bar­gain.

About 36 per­cent of pa­tients who go in­to re­mis­sion with Kym­ri­ah re­lapse with­in one year, said Dr. Vinay Prasad, an as­sis­tant pro­fes­sor of med­i­cine at Ore­gon Health & Sci­ence Uni­ver­si­ty. Many of these pa­tients will need ad­di­tion­al treat­ment, said Prasad, who wrote an ed­i­to­r­i­al about Kym­ri­ah’s price Oct. 4 in Na­ture.

“If you’ve paid half a mil­lion dol­lars for drugs and half a mil­lion dol­lars for care, and a year lat­er your can­cer is back, is that a good deal?” asked Saltz, who co-wrote a re­cent ed­i­to­r­i­al on Kym­ri­ah’s price in JA­MA.

Dr. Steve Miller, chief med­ical of­fi­cer for Ex­press Scripts, a phar­ma­cy ben­e­fit man­ag­er, said it would be more fair to judge Kym­ri­ah’s suc­cess af­ter six months of treat­ment, rather than one month. Prasad goes even fur­ther. He said No­var­tis should is­sue re­funds for any pa­tient whose leukemia re­laps­es with­in three years.

A con­sumer ad­vo­cate group called Pa­tients for Af­ford­able Drugs al­so has said that Kym­ri­ah costs too much, giv­en that the fed­er­al gov­ern­ment spent more than $200 mil­lion over two decades to sup­port the ba­sic re­search in­to CAR T-cell ther­a­py, long be­fore No­var­tis bought the rights.

Rep. Lloyd Doggett, D-Texas, wrote a let­ter to the Medicare pro­gram’s di­rec­tor last month ask­ing for de­tails on how the No­var­tis pay­ment deal will work.

“As Big Phar­ma con­tin­ues to put price goug­ing be­fore pa­tient ac­cess, com­pa­nies will point more and more proud­ly at their pric­ing agree­ments,” Doggett wrote. “But tax­pay­ers de­serve to know more about how these agree­ments will work — whether they will ac­tu­al­ly save the gov­ern­ment mon­ey, de­fray these mas­sive costs, and en­sure that they can ac­cess life-sav­ing med­ica­tions.”

By Liz Sz­abo. Orig­i­nal­ly post­ed at Kaiser Health News, a na­tion­al health pol­i­cy news ser­vice that is part of the non­par­ti­san Hen­ry J Kaiser Fam­i­ly Foun­da­tion.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

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Milner’s question on one of those mornings on foot: “What do you want to do?”

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Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

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Bil­lion­aires Chamath Pal­i­hapi­tiya and Pablo Legor­re­ta hatch an $825M SPAC for cell ther­a­py biotech

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ProKidney was founded 6 years ago but really got going at the beginning of 2019 with the $62 million acquisition of inRegen, which was working on an autologous — from the patient — cell therapy for kidney disease. After extracting kidney cells from patients, researchers expand the cells in the lab and then inject them back into patients, aiming to restore the kidneys of patients suffering from CKD.

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CBO: Medicare ne­go­ti­a­tions will ham­per drug de­vel­op­ment more than pre­vi­ous­ly thought

As President Biden’s Build Back Better Act — and, with it, potentially the Democrats’ last shot at major drug pricing reforms in the foreseeable future — remains on life support, the Congressional Budget Office isn’t helping their case.

The CBO last week released a new slide deck, outlining an update to its model on how Medicare negotiations might take a bite out of new drugs making it to market. The new model estimates a 10% long-term reduction in the number of new drugs, whereas a previous CBO report from August estimated that 8% fewer new drugs will enter the market over 30 years.

Joshua Brumm, Dyne Therapeutics CEO

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Dyne Therapeutics’ stock took a nasty hit this morning after the biotech put out word that the FDA had slapped a clinical hold on their top program for Duchenne muscular dystrophy. And now speculation is bouncing around Biotwitter that there could be a class effect at work here that would implicate other drug developers in the freeze.

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Michel Vounatsos, Biogen CEO (Credit: World Economic Forum/Ciaran McCrickard)

An un­ortho­dox pro­pos­al for Bio­gen's Medicare-man­dat­ed Aduhelm tri­al

Biogen has gone full blitz since Medicare announced it would only cover its new Alzheimer’s drug when used in clinical trials, accusing the agency of discriminating against Alzheimer’s patients and trying to get physicians to change regulators’ minds.  Critics, meanwhile, cheered what they see as a necessary wall protecting payers and patients from an unproven and unsafe drug.

Far less attention, though, has gone to what a Medicare-funded clinical trial would actually look like. Biogen has operated as if it would be a standard late-stage Alzheimer’s trial, enrolling a couple thousand patients and giving half placebo.

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