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.

Donald and Melania Trump watch the smoke of fireworks from the South Lawn of the White House on July 4, 2020 (via Getty)

Which drug de­vel­op­ers of­fer Trump a quick, game-chang­ing ‘so­lu­tion’ as the pan­dem­ic roars back? Eli Lil­ly and Ab­Cellera look to break out of the pack

We are unleashing our nation’s scientific brilliance and will likely have a therapeutic and/or vaccine solution long before the end of the year.

— Donald Trump, July 4

Next week administration officials plan to promote a new study they say shows promising results on therapeutics, the officials said. They wouldn’t describe the study in any further detail because, they said, its disclosure would be “market-moving.”

— NBC News, July 3

Something’s cooking. And it’s not just July 4 leftovers involving stale buns and uneaten hot dogs.

Over the long weekend observers picked up signs that the focus in the Trump administration may swiftly shift from the bright spotlight on vaccines being promised this fall, around the time of the election, to include drugs that could possibly keep patients out of the hospital and take the political sting out of the soaring Covid-19 numbers causing embarrassment in states that swiftly reopened — as Trump cheered along.

So far, Gilead has been the chief beneficiary of the drive on drugs, swiftly offering enough early data to get remdesivir an emergency authorization and into the hands of the US government. But their drug, while helpful in cutting stays, is known for a limited, modest effect. And that won’t tamp down on the hurricane of criticism that’s been tearing at the White House, and buffeting the president’s most stalwart core defenders as the economy suffers.

We’ve had positive early-stage vaccine data, most recently from Pfizer and BioNTech, playing catchup on an mRNA race led by Moderna — where every little sign of potential trouble is magnified into a lethal threat, just as every advance excites a frenzy of support. But that race still has months to play out, with more Phase I data due ahead of the mid-stage numbers looming ahead. A vaccine may not be available in large enough quantities until well into 2021, which is still wildly ambitious.

So what about a drug solution?

Trump’s initial support for a panacea focused on hydroxychloroquine. But that fizzled in the face of data underscoring its ineffectiveness — killing trials that aren’t likely to be restarted because of a recent population-based study offering some support. And there are a number of existing drugs being repurposed to see how they help hospitalized patients.

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Shoshanna Shendelman, Applied Therapeutics CEO (Applied Therapeutics)

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As short attacks go, Biotech Research Partners’ assault on Applied Therapeutics’ “cherry picked” data and a variety of so-called red flags didn’t cause a whole lot of damage. Ahead of the July 4 holiday, its shares $APLT were dinged and showed signs of quick recovery.

But that didn’t stop an incendiary response, as the biotech swung into action bright and early Monday morning.

Applied Therapeutics accused the authors of the short report of manipulating graphs and figures, misrepresenting data and included factual misrepresentations — all of which added up, in their view, to fraud.

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The multiple myeloma patient had previously been treated unsuccessfully with various therapies, noted the biotech, and had been given dose level two (DL2) of their allogeneic CAR-T.

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UP­DAT­ED: Im­munomedics spells out PFS ben­e­fit of Trodelvy in mTNBC, hunt­ing a full OK just weeks af­ter ac­cel­er­at­ed ap­proval

By the time the FDA finally granted an accelerated OK for Immunomedics’ Trodelvy, we already got a very strong hint that their confirmatory Phase III study in metastatic triple-negative breast cancer was a success.

That’s because the independent data safety monitoring committee recommended that the trial be stopped early. But just what pointed them to the conclusion was still unclear.

“We do not know the totality of their decision other than it’s pretty evident that the primary endpoint was met; otherwise they could not request to halt the study,” Behzad Aghazadeh, the executive chairman, told Endpoints News at the time.

Bill Haney, Dragonfly CEO (Dave Pedley/Getty Images for SXSW)

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Covid-19 roundup: Teamed up with NIH, Re­gen­eron launch­es PhI­II pre­ven­tion tri­al for an­ti­body cock­tail

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Douglas Love, Annexon CEO (Annexon)

IPO bound? Ac­tu­al­ly, An­nex­on was al­ready prepped and primed to toss its S-1 to Wall Street as in­vestors ral­lied

The Wall Street IPO shuffle generally calls for a little distance between the crossover ante and the Wall Street double, but with the window on the street wide open and biotech sizzling hot, who’s waiting?

The crew at Annexon didn’t leave anyone in suspense for long about their IPO plans. A day after the Bay Area biotech with clinical plans to target neurodegeneration quietly unveiled a $100 million raise, they were back with an S-1 outlining a pitch to double that — or more.

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Elias Zerhouni (Photo by Vincent Isore/IP3/Getty Images)

Elias Zer­houni dis­cuss­es ‘am­a­teur hour’ in DC, the de­struc­tion of in­fec­tious dis­ease R&D and how we need to prep for the next time

Elias Zerhouni favors blunt talk, and in a recent discussion with NPR, the ex-Sanofi R&D and ex-NIH chief had some tough points to make regarding the pandemic response.

Rather than interpret them, I thought it would be best to provide snippets straight from the interview.

On the Trump administration response:

It was basically amateur hour. There is no central concept of operations for preparedness, for pandemics, period. This administration doesn’t want to or has no concept of what it takes to protect the American people and the world because it is codependent. You can’t close your borders and say, “OK, we’re going to be safe.” You’re not going to be able to do that in this world. So it’s a lack of vision, basically just a lack of understanding, of what it takes to protect the American people.

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Jean-Paul Clozel, Idorsia CEO (Patrick Straub/Keystone via AP Images)

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Following a successful Phase III study in April showcasing the safety and potential of its new sleep drug, Idorsia posted some mixed news in the second Phase III study, but that won’t stop a planned filing aimed at regulatory approval.

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