#ASH17: How does No­var­tis’ Kym­ri­ah DL­B­CL da­ta stack up head­ing straight to a CAR-T show­down with Gilead?

No­var­tis turned up at ASH with 6-month da­ta for their pi­o­neer­ing CAR-T Kym­ri­ah that puts them on the in­side track to a quick and near-cer­tain ap­proval for a sec­ond in­di­ca­tion to treat DL­B­CL — and straight in­to a com­mer­cial show­down with Gilead/Kite.

Al­ready snagged as the first in­di­ca­tion to be OK’d for Gilead/Kite’s Yescar­ta, No­var­tis’ in­ves­ti­ga­tors nailed down re­mark­ably sim­i­lar ef­fi­ca­cy da­ta at the 6-month mark that close­ly mir­rors their ri­val. But even with the match­ing out­comes on ef­fi­ca­cy, No­var­tis’ team still feels that they have a clear mar­ket­ing edge on the safe­ty front.

Don’t ex­pect an ag­gres­sive Gilead, though, to shy from the mar­ket­ing con­fronta­tion that’s about to loom. Their CAR-T was the first to get out from on DL­B­CL, and the Kite team up­dat­ed their da­ta to­day to re­flect some out­stand­ing ev­i­dence of dura­bil­i­ty, which will en­cour­age every­one de­vel­op­ing CAR-T ther­a­pies. (More on that, be­low.)

The No­var­tis re­searchers tracked a slide in re­sults for the 3-month mark, but start­ed at some­what high­er lev­els than Gilead/Kite that left them side-by-side.

Here’s their com­par­i­son, with the stan­dard caveat that sci­en­tists hate it when an­a­lysts line p da­ta from dif­fer­ent stud­ies.

At six months from in­fu­sion, the ORR for Kym­ri­ah was 37% with a com­plete re­sponse rate of 30%. The me­di­an du­ra­tion of re­sponse was not reached. At three months the in­ter­im over­all re­sponse rate dis­cussed at AS­CO hit 45% among 23 of 51 pa­tients eval­u­at­ed with an im­pres­sive 37% achiev­ing a com­plete re­sponse and 8% achiev­ing a par­tial re­sponse.

For Gilead/Kite: At 6 months, the ORR in dif­fuse large B-cell lym­phoma (DL­B­CL) hit 36%, down three points from month three. The CR rate was 31%, down two points.

“Most of the drop-off are the par­tial re­spon­ders, in CRs there’s a very small drop off,” says David Leb­wohl, an SVP and No­var­tis’ fran­chise glob­al pro­gram chief.

Leb­wohl al­so high­light­ed a 73.5% re­lapse-free rate. The me­di­an PFS rate was not yet es­tab­lished.

Where Lebe­wohl and his col­leagues be­lieve they can draw a more dis­tinct dif­fer­ence with the com­pe­ti­tion is on the safe­ty pro­file. To be sure, Kym­ri­ah wasn’t free of ad­verse events. Close to one in four ex­pe­ri­enced grade 3 or 4 cy­tokine re­lease syn­drome. And 12% had a grade 3 or 4 episode in­volv­ing neu­ro­tox­i­c­i­ty. How­ev­er, no one died and they man­aged the AEs.

No­var­tis is al­so get­ting its hands on the man­u­fac­tur­ing is­sues that pre­vent­ed 11 pa­tients from be­ing treat­ed, with a 97% suc­cess rate for the last 30 pa­tients. That’s cru­cial if No­var­tis ex­pects to suc­cess­ful­ly go up against the Kite time.

Pas­cal Tou­chon

I asked Leb­wohl and Pas­cal Tou­chon, SVP, glob­al head cell and gene, about their vein-to-vein times, the turn­around that marks the amount of time that a man­u­fac­tur­er takes from the time cells are ex­tract­ed from pa­tients to the time it takes to in­fuse them back in.

The biotech, bought out by Gilead for $12 bil­lion, had drilled that down to 17 days, with plans to shave a few more days off.

No­var­tis, though, doesn’t like the “vein-to-vein” stan­dard. With cry­op­reser­va­tion af­ter aphere­sis the big phar­ma prefers to track the time from re­ceipt of cells to their re­turn, giv­ing physi­cians flex­i­bil­i­ty on tim­ing re-in­fu­sion. How that plays with pa­tients anx­ious to be treat­ed, though, has yet to be seen.

Now let’s switch back to Gilead and Yescar­ta.

To eval­u­ate the dura­bil­i­ty of Yescar­ta re­spons­es, their re­search team com­plet­ed an up­dat­ed analy­sis on more than 100 pa­tients in ZU­MA-1 who had been fol­lowed for a min­i­mum of one year. The bot­tom line:

In this up­dat­ed analy­sis, 82 per­cent of pa­tients had re­spond­ed to Yescar­ta, in­clud­ing 58 per­cent of pa­tients who had achieved com­plete re­mis­sion. At a me­di­an of 15.4 months post-in­fu­sion, 42 per­cent of pa­tients re­mained in re­sponse, in­clud­ing 40 per­cent in com­plete re­mis­sion. The me­di­an du­ra­tion of re­sponse was 11.1 months (95 per­cent CI: 3.9 months to not es­timable [NE]); in pa­tients who have achieved a com­plete re­mis­sion, the me­di­an du­ra­tion of re­sponse was not reached (95 per­cent CI: NE). Me­di­an over­all sur­vival had not been reached (95 per­cent CI: 12 months to NE) with an over­all sur­vival rate at 18 months of 52 per­cent (95 per­cent CI: 41 to 62).

That qual­i­fies as an­oth­er ma­jor step for­ward.

Look for an­oth­er vir­tu­al snap de­ci­sion from the FDA for No­var­tis. The agency is hur­ry­ing along fol­lowup in­di­ca­tion de­ci­sions, par­tic­u­lar­ly on their spot­light break­through pro­grams. And Leb­wohl says No­var­tis is ready to roll, once the green light hits.


As Nas­daq en­rolls the fi­nal batch of 2019 IPOs, how have the num­bers com­pared to past years?

IGM Biosciences’ upsized IPO haul, coming after SpringWorks’ sizable public debut, has revved up some momentum for the last rush of biotech IPOs in 2019.

With 39 new listings on the books and roughly two more months to go before winding down, Nasdaq’s head of healthcare listings Jordan Saxe sees the exchange marking 50 to 60 biopharma IPOs for the year.

“December 15 is usually the last possible day that companies will price,” he said, as companies get ready for business talks at the annual JP Morgan Healthcare Conference in January.

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A fa­vorite in Alex­ion’s C-suite is leav­ing, and some mighty sur­prised an­a­lysts aren’t the least bit hap­py about it

Analysts hate to lose a biotech CFO they’ve come to trust and admire — especially if they’re being blindsided by a surprise exit.

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David Grainger [file photo]

'Dis­con­nect the bas­tard­s' — one biotech's plan to break can­cer cell­s' uni­fied de­fens­es

Chemotherapy and radiotherapy are the current gladiators of cancer treatment, but they come with well-known limitations and side-effects. The emergence of immunotherapy — a ferocious new titan in oncologist’s toolbox — takes the brakes off the immune system to kill cancer cells with remarkable success in some cases, but the approach is not always effective. What makes certain forms of cancer so resilient? Scientists may have finally pieced together a tantalizing piece of the puzzle, and a new biotech is banking on a new approach to fill the gap.

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While No­var­tis ban­ish­es Zol­gens­ma scan­dal scars — Bio­gen goes on a Spin­raza 'of­fen­sive'

While Novartis painstakingly works to mop up the stench of the data manipulation scandal associated with its expensive gene therapy for spinal muscular atrophy (SMA) Zolgensma— rival Biogen is attempting to expand the use of its SMA therapy, Spinraza. 

The US drugmaker $BIIB secured US approval for Spinraza for use in the often fatal genetic disease in 2016. The approval covered a broad range of patients with infantile-onset (most likely to develop Type 1) SMA. 

Jason Kelly. Mike Blake/Reuters via Adobe

Eye­ing big ther­a­peu­tic push, Gink­go bags $290M to build a cell pro­gram­ming em­pire

Ginkgo Bioworks is on a roll. Days after publicizing a plan to nurture new startups via partnerships with accelerators Y Combinator and Petri, the Boston biotech says it has raised another $290 million for its cell programming platform to reach further and wider.

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UP­DAT­ED: Speak­er Nan­cy Pelosi to un­veil bill for fed­er­al­ly ne­go­ti­at­ed drug prices

After months of buzz from both sides of the aisle, Speaker Nancy Pelosi will today introduce her plan to allow the federal government to negotiate prices for 250 prescription drugs, setting up a showdown with a pharmaceutical industry working overtime to prevent it.

The need to limit drug prices is a rare point of agreement between President Trump and Democrats, although the president has yet to comment on the proposal and will likely face pressure to back a more conservative option or no bill at all. Republican Senator Chuck Grassley is reportedly lobbying his fellow party members on a more modest proposal he negotiated with Democratic Senator Ron Wyden in July.

Jeff Kindler's Cen­trex­ion re­news bid to make pub­lic de­but

Jeffrey Kindler’s plan to take his biotech — which is developing a slate of non-opioid painkillers — public, is back on.

The Boston based company, led by former Pfizer $PFE chief Kindler, originally contemplated a $70 million to $80 million IPO last year— but eventually postponed that strategy. On Wednesday, the company revived its bid to make a public debut in a filing with the SEC — although no pricing details were disclosed.

Zachary Hornby. Boundless

'A fourth rev­o­lu­tion in can­cer ther­a­pies': ARCH-backed Bound­less Bio flash­es big check, makes big­ger promis­es in de­but

It was the cellular equivalent of opening your car door and finding an active, roaring engine in the driver seat.

Scientists learned strands of DNA could occasionally appear outside of its traditional home in the nucleus in the 1970s, when they appeared as little, innocuous circles on microscopes; inexplicable but apparently innate. But not until UC San Diego’s Paul Mischel published his first study in Science in 2014 did researchers realize these circles were not only active but potentially overactive and driving some cancer tumors’ superhuman growth.

Scott Gottlieb, AP Images

Scott Got­tlieb is once again join­ing a team that en­joyed good times at the FDA un­der his high-en­er­gy stint at the helm

Right after jumping on Michael Milken’s FasterCures board on Monday, the newly departed FDA commissioner is back today with news about another life sciences board post that gives him a ringside chair to cheer on a lead player in the real-world evidence movement — one with very close ties to the FDA.

Aetion is reporting this morning that Gottlieb is joining their board, a group that includes Mohamad Makhzoumi, a general partner at New Enterprise Associates, where Gottlieb returned after stepping out of his role at the FDA 2 years after he started.

Gottlieb — one of the best connected execs in biopharma — knows this company well. As head of FDA he championed the use of real-world evidence to help guide drug developers and the agency in gaining greater efficiencies, which helped set up Aetion as a high-profile player in the game.

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