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.

Chica­go biotech ar­gues blue­bird, Third Rock 'killed' its ri­val, pi­o­neer­ing tha­lassemia gene ther­a­py in law­suit

Blue­bird bio $BLUE chief Nick Leschly court­ed con­tro­ver­sy last week when he re­vealed the com­pa­ny’s be­ta tha­lassemia treat­ment will car­ry a jaw-drop­ping $1.8 mil­lion price tag over a 5 year pe­ri­od in the Unit­ed States — mak­ing it the plan­et’s sec­ond most ex­pen­sive ther­a­py be­hind No­var­tis’ $NVS fresh­ly ap­proved spinal mus­cu­lar at­ro­phy ther­a­py, Zol­gens­ma at $2.1 mil­lion. A Chica­go biotech, mean­while, has been fum­ing at the side­lines. In a law­suit filed ear­li­er this month, Er­rant Gene Ther­a­peu­tics al­leged that blue­bird and ven­ture cap­i­tal group Third Rock un­law­ful­ly prised a vi­ral vec­tor, de­vel­oped in part­ner­ship with the Memo­r­i­al Sloan Ket­ter­ing (MSK), from its grasp, and thwart­ed the de­vel­op­ment of its sem­i­nal gene ther­a­py.

Arc­turus ex­pands col­lab­o­ra­tion, adding $30M cash; Ku­ra shoots for $100M raise

→  Rare dis­ease play­er Ul­tragenyx $RARE is ex­pand­ing its al­liance with Arc­turus $ARCT, pay­ing $24 mil­lion for eq­ui­ty and an­oth­er $6 mil­lion in an up­front as the two part­ners ex­pand their col­lab­o­ra­tion to in­clude up to 12 tar­gets. “This ex­pand­ed col­lab­o­ra­tion fur­ther so­lid­i­fies our mR­NA plat­form by adding ad­di­tion­al tar­gets and ex­pand­ing our abil­i­ty to po­ten­tial­ly treat more dis­eases,” said Emil Kakkis, the CEO at Ul­tragenyx. “We are pleased with the progress of our on­go­ing col­lab­o­ra­tion. Our most ad­vanced mR­NA pro­gram, UX053 for the treat­ment of Glyco­gen Stor­age Dis­ease Type III, is ex­pect­ed to move in­to the clin­ic next year, and we look for­ward to fur­ther build­ing up­on the ini­tial suc­cess of this part­ner­ship.”

Neil Woodford. Woodford Investment Management via YouTube

Wood­ford braces po­lit­i­cal storm as UK fi­nan­cial reg­u­la­tors scru­ti­nize fund sus­pen­sion

The shock of Neil Wood­ford’s de­ci­sion to block with­drawals for his flag­ship fund is still rip­pling through the rest of his port­fo­lio — and be­yond. Un­der po­lit­i­cal pres­sure, UK fi­nan­cial reg­u­la­tors are now tak­ing a hard look while in­vestors con­tin­ue to flee.

In a re­sponse let­ter to an MP, the Fi­nan­cial Con­duct Au­thor­i­ty re­vealed that it’s opened an in­ves­ti­ga­tion in­to the sus­pen­sion fol­low­ing months of en­gage­ment with Link Fund So­lu­tions, which tech­ni­cal­ly del­e­gat­ed Wood­ford’s firm to man­age its funds.

The top 10 block­buster drugs in the late-stage pipeline — Eval­u­ate adds 6 new ther­a­pies to heavy-hit­ter list

Vertex comes in for a substantial amount of criticism for its no-holds-barred tactical approach toward wresting the price it wants for its commercial drugs in Europe. But the flip side of that coin is a highly admired R&D and commercial operation that regularly wins kudos from analysts for their ability to engineer greater cash flow from the breakthrough drugs they create.

Both aspects needed for success in this business are on display in the program backing Vertex’s triple for cystic fibrosis. VX-659/VX-445 + Tezacaftor + Ivacaftor — it’s been whittled down to 445 now — was singled out by Evaluate Pharma as the late-stage therapy most likely to win the crown for drug sales in 5 years, with a projected peak revenue forecast of $4.3 billion.

The latest annual list, which you can see here in their latest world preview, includes a roster of some of the most closely watched development programs in biopharma. And Evaluate has added 6 must-watch experimental drugs to the top 10 as drugs fail or go on to a first approval. With apologies to the list maker, I revamped this to rank the top 10 by projected 2024 sales, instead of Evaluate's net present value rankings.

It's how we roll at Endpoints News.

Here is a quick summary of the rest of the top 10:

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Gilead baits new al­liance with $45M up­front, div­ing in­to the busy pro­tein degra­da­tion field

Gilead is jump­ing on board the pro­tein degra­da­tion band­wag­on. And they’re turn­ing to a low-pro­file Third Rock start­up for the ex­per­tise. But if you were look­ing for a trans­for­ma­tion­al deal to kick up fresh en­thu­si­asm for Gilead, you’ll have to re­main pa­tient.

 

This one will have a long way to go be­fore they get in­to the clin­ic.

The big biotech said Wednes­day morn­ing that it is pay­ing $45 mil­lion up­front and re­serv­ing a whop­ping $2.3 bil­lion in biotech bucks if San Fran­cis­co-based Nurix can point the way to new can­cer ther­a­pies, as well as drugs for oth­er, un­spec­i­fied dis­eases.

John Chiminski, Catalent CEO - File Photo

'It's a growth play': Catal­ent ac­quires Bris­tol-My­er­s' Eu­ro­pean launch pad, ex­pand­ing glob­al CD­MO ops

Catalent is staying on the growth track.

Just two months after committing $1.2 billion to pick up Paragon and take a deep dive into the sizzling hot gene therapy manufacturing sector, the CDMO is bouncing right back with a deal to buy out Bristol-Myers’ central launchpad for new therapies in Europe, acquiring a complex in Anagni, Italy, southwest of Rome, that will significantly expand its capacity on the continent.

There are no terms being offered, but this is no small deal. The Anagni campus employs some 700 staffers, and Catalent is planning to go right in — once the deal closes late this year — with a blueprint to build up the operations further as they expand on oral solid, biologics, and sterile product manufacturing and packaging.

This is an uncommon deal, Catalent CEO John Chiminski tells me. But it offers a shortcut for rapid growth that cuts years out of developing a green fields project. That’s time Catalent doesn’t have as the industry undergoes unprecedented expansion around the world.

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A new num­ber 1 drug? Keytru­da tapped to top the 10 biggest block­busters on the world stage by 2024

Analysts may be fretting about Keytruda’s longterm prospects as a host of rival therapies elbow their way to the market. But the folks at Evaluate Pharma are confident that last year’s $7 billion earner is headed for glory, tapping it to beat out the current #1 therapy Humira as AbbVie watches that franchise swoon over the next 5 years.

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In­vestor day prep at Mer­ck in­cludes a new strat­e­gy to pick up the pace on M&A — re­port

Mer­ck’s re­cent deals to buy up two bolt-on biotechs — Ti­los and Pelo­ton — weren’t an aber­ra­tion. In­stead, both ac­qui­si­tions mark a new strat­e­gy to beef up its dom­i­nant can­cer drug op­er­a­tions cen­tered on Keytru­da while look­ing to ad­dress grow­ing con­cerns that too many of its eggs are in the one I/O bas­ket for their PD-1 pro­gram. And Mer­ck is go­ing af­ter more small- and mid-sized buy­outs to calm those fears.

Dave Barrett, Brian Chee, Amir Nashat, Amy Schulman. Polaris

Bob Langer's first port of call — Po­laris Part­ners — maps $400M for ninth fund

Health and tech ven­ture group Po­laris Part­ners, which counts Alec­tor, Al­ny­lam and Ed­i­tas Med­i­cine as part of its port­fo­lio, is set­ting up its ninth fund, rough­ly two years af­ter it closed Po­laris VI­II with $435 mil­lion in the bank, sur­pass­ing its tar­get by $35 mil­lion.

The Boston-based firm, in an SEC fil­ing, said it in­tends to raise $400 mil­lion for the fund. Po­laris — which rou­tine­ly backs com­pa­nies mold­ed out of the work done in the lab of pro­lif­ic sci­en­tist Bob Langer of MIT  — typ­i­cal­ly in­vests ear­ly, and sticks around till com­pa­nies are in the green. Like its peers at Flag­ship and Third Rock, Po­laris is all about cham­pi­oning the lo­cal biotech scene with a steady flow of start­up cash.