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.

De­vel­op­ment of the Next Gen­er­a­tion NKG2D CAR T-cell Man­u­fac­tur­ing Process

Celyad’s view on developing and delivering a CAR T-cell therapy with multi-tumor specificity combined with cell manufacturing success
Overview
Transitioning potential therapeutic assets from academia into the commercial environment is an exercise that is largely underappreciated by stakeholders, except for drug developers themselves. The promise of preclinical or early clinical results drives enthusiasm, but the pragmatic delivery of a therapy outside of small, local testing is most often a major challenge for drug developers especially, including among other things, the manufacturing challenges that surround the production of just-in-time and personalized autologous cell therapy products.

Paul Hudson, Getty Images

UP­DAT­ED: Sanofi CEO Hud­son lays out new R&D fo­cus — chop­ping di­a­betes, car­dio and slash­ing $2B-plus costs in sur­gi­cal dis­sec­tion

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy presentation Tuesday with a tell-tale deal to buy Synthorx for $2.5 billion. That fits squarely with hints that he’s pointing the company to a bigger future in oncology, which also squares with a major industry tilt.

In a big reveal later in the day, though, Hudson offered a slate of stunners on his plans to surgically dissect and reassemble the portfoloio, saying that the company is dropping cardio and diabetes research — which covers two of its biggest franchise arenas. Sanofi missed the boat on developing new diabetes drugs, and now it’s pulling out entirely. As part of the pullback, it’s dropping efpeglenatide, their once-weekly GLP-1 injection for diabetes.

“To be out of cardiovascular and diabetes is not easy for a company like ours with an incredibly proud history,” Hudson said on a call with reporters, according to the Wall Street Journal. “As tough a choice as that is, we’re making that choice.”

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Paul Hudson, Sanofi

Paul Hud­son promis­es a bright new fu­ture at Sanofi, kick­ing loose me-too drugs and fo­cus­ing on land­mark ad­vances. But can he de­liv­er?

Paul Hudson was on a mission Tuesday morning as he stood up to address Sanofi’s new R&D and business strategy.

Still fresh into the job, the new CEO set out to convince his audience — including the legions of nervous staffers inevitably devoting much of their day to listening in — that the pharma giant is shedding the layers of bureaucracy that had held them back from making progress in the past, dropping the duds in the pipeline and reprioritizing a more narrow set of experimental drugs that were promised as first-in-class or best-in-class.  The company, he added, is now positioned to “go after other opportunities” that could offer a transformational approach to treating its core diseases.

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Left top to right: Mark Timney, Alex Denner, Vas Narasimhan. (The Medicines Company, Getty, AP/Endpoints News)

In a play-by-play of the $9.7B Med­Co buy­out, No­var­tis ad­mits it over­paid while of­fer­ing a huge wind­fall to ex­ecs

A month into his tenure at The Medicines Company, new CEO Mark Timney reached out to then-Novartis pharma chief Paul Hudson: Any interest in a partnership?

No, Hudson told him. Not now, at least.

Ten months later, Hudson had left to run Sanofi and Novartis CEO Vas Narasimhan was paying $9.7 billion for the one-drug biotech – the largest in the string of acquisitions Narasimhan has signed since his 2017 appointment.

The deal was the product of an activist investor and his controversial partner working through nearly a year of cat-and-mouse negotiations to secure a deal with Big Pharma’s most expansionist executive. It represented a huge bet in a cardiovascular field that already saw two major busts in recent years and brought massive returns for two of the industry’s most eye-raising names.

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Roger Perlmutter, Merck

#ASH19: Here’s why Mer­ck is pay­ing $2.7B to­day to grab Ar­Qule and its next-gen BTK drug, lin­ing up Eli Lil­ly ri­val­ry

Just a few months after making a splash at the European Hematology Association scientific confab with an early snapshot of positive data for their BTK inhibitor ARQ 531, ArQule has won a $2.7 billion buyout deal from Merck.

Merck is scooping up a next-gen BTK drug — which is making a splash at ASH today — from ArQule in an M&A pact set at $20 a share $ARQL. That’s more than twice Friday’s $9.66 close. And Merck R&D chief Roger Perlmutter heralded a deal that nets “multiple clinical-stage oral kinase inhibitors.”

This is the second biotech buyout pact today, marking a brisk tempo of M&A deals in the lead-up to the big JP Morgan gathering in mid-January. It’s no surprise the acquisitions are both for cancer drugs, where Sanofi will try to make its mark while Merck beefs up a stellar oncology franchise. And bolt-ons are all the rage at the major pharma players, which you could also see in Novartis’ recent $9.7 billion MedCo buyout.

ArQule — which comes out on top after their original lead drug foundered in Phase III — highlighted early data on ‘531 at EHA from a group of 6 chronic lymphocytic leukemia patients who got the 65 mg dose. Four of them experienced a partial response — a big advance for a company that failed with earlier attempts.

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Paul Hudson. Sanofi

New Sanofi CEO Hud­son adds next-gen can­cer drug tech to the R&D quest, buy­ing Syn­thorx for $2.5B

When Paul Hudson lays out his R&D vision for Sanofi tomorrow, he will have a new slate of interleukin therapies and a synthetic biology platform to boast about.

The French pharma giant announced early Monday that it is snagging San Diego biotech Synthorx in a $2.5 billion deal. That marks an affordable bolt-on for Sanofi but a considerable return for Synthorx backers, including Avalon, RA Capital and OrbiMed: At $68 per share, the price represents a 172% premium to Friday’s closing.

Synthorx’s take on alternative IL-2 drugs for both cancer and autoimmune disorders — enabled by a synthetic DNA base pair pioneered by Scripps professor Floyd Romesberg — “fits perfectly” with the kind of innovation that he wants at Sanofi, Hudson said.

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Am­gen puts its foot down in shiny new South San Fran­cis­co hub as it re­or­ga­nizes R&D ops

Amgen has signed up to be AbbVie’s neighbor in South San Francisco as it moves into a nine-story R&D facility in the booming biotech hub.

The arrangement gives Amgen 240,000 square feet of space on the Gateway of Pacific Campus, just a few minutes drive from its current digs at Oyster Point. The new hub will open in 2022 and house the big biotech’s Bay Area employees working on cardiometabolic, inflammation and oncology research.

Ab­b­Vie, Scripps ex­pand part­ner­ship, for­ti­fy fo­cus on can­cer drugs

Scripps and AbbVie go way back. Research conducted in the lab of Scripps scientist Richard Lerner led to the discovery of Humira. The antibody, approved by the FDA in 2002 and sold by AbbVie, went on to become the world’s bestselling treatment. In 2018, the drugmaker and the non-profit organization signed a pact focused on developing cancer treatments — and now, the scope of that partnership has broadened to encompass a range of diseases, including immunological and neurological conditions.

South Ko­rea jails 3 Sam­sung ex­ecs for de­stroy­ing ev­i­dence in Bi­o­Log­ics probe

Three Samsung executives in Korea are going to jail.

The convictions came in what prosecutors had billed as “biggest crime of evidence destruction in the history of South Korea”: a case of alleged corporate intrigue that was thrown open when investigators found what was hidden beneath the floor of a Samsung BioLogics plant. Eight employees in total were found guilty of evidence tampering and the three executives were each sentenced to up to two years in prison.