#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.

 

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

Jason Kelly, Ginkgo Bioworks CEO (Kyle Grillot/Bloomberg via Getty Images)

UP­DAT­ED: Gink­go Bioworks re­sizes the de­f­i­n­i­tion of go­ing big in biotech, rais­ing $2.5B in a record SPAC deal that weighs in with a whop­ping $15B-plus val­u­a­tion

Ginkgo Bioworks execs always thought big. But today should redefine just how big an upstart biotech player can dream.

In the largest SPAC deal to clear the hurdles to Nasdaq, the biotech that envisioned everything from remaking synthetic meat to a whole new approach to developing drugs has joined forces with one of the biggest disruptors in biotech to slam the Richter scale on dealmaking.

Soon after becoming the darling of the VC crew and clearing the bar on a $4 billion valuation, Ginkgo — a synthetic biotech player out to reprogram cells with industrial efficiency — has now struck a deal to go public in the latest leviathan SPAC that sets its pre-money valuation at $15 billion. In one swift vault, Ginkgo will combine with Harry Sloan’s Soaring Eagle Acquisition Corp. and leap into the public markets.

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FDA un­veils six ICH guide­lines ahead of meet­ing with Health Cana­da

A sign that the FDA’s non-Covid-related processes are beginning to normalize: The release of six guidelines from the International Council of Harmonisation.

Years in development, the ICH documents offer an international perspective on drug development, with these latest guidelines covering everything from recommendations to support the classification of drug substances, featured in the M9 guidance, to standards for nonclinical safety studies for pediatric medicines in the S11 guideline.

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Sanofi, Glax­o­SmithK­line, Boehringer ac­cused of play­ing games, de­stroy­ing emails re­lat­ed to law­suit over con­t­a­m­i­nat­ed Zan­tac

A recent court filing raises new questions about how major pharma companies like Sanofi, GlaxoSmithKline, and Boehringer Ingelheim have dealt with a lawsuit related to recalls of certain over-the-counter heartburn drugs due to the presence of a potentially cancer-causing substance found in them.

More than 70,000 people who took Sanofi’s Zantac and other heartburn drugs containing ranitidine, which have been recalled over the past two years, have sued the manufacturers, including generic drugmakers, and other retailers and distributors as part of a consolidated suit before US District Court Judge Robin Rosenberg in Florida.

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Al Sandrock, Biogen R&D chief (Biogen via YouTube)

UP­DAT­ED: Bio­gen push­es in a fresh stack of chips and starts prep­ping a glob­al R&D game plan af­ter watch­ing the cards turn on ear­ly throm­bolyt­ic da­ta

After patiently steering through a decade-long journey for its early-stage clinical work, a small Tokyo biotech has clinched a deal to out-license its lead thrombolytic agent to US heavyweight Biogen — which sees a potentially game-changing impact on the clot-busting field after taking a careful look at some upbeat Phase IIa data.

Three years after Biogen anted up $4 million to gain an option on the drug from TMS, the big US biotech is making a small bet to beef up its stroke portfolio. The BD team inked a deal to go ahead and grab rights to the drug for $18 million, with another $335 million in milestone cash on the table for a successful outcome.

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Chris Garabedian (Xontogeny)

Per­cep­tive Ad­vi­sors, Xon­toge­ny bring the band back and then some with a $515M sec­ond fund sniff­ing out lead com­pounds

When Perceptive Advisors and startup accelerator Xontogeny initially teamed up on an early-stage VC round in 2019, the partners hoped to prove their investments could be a force multiplier for early-stage companies. Now, with that proof of concept behind them, the pair have closed a second VC round worth more than double the money.

Dubbed PXV Fund II and headed by Xontogeny CEO and former Sarepta head Chris Garabedian, the $515 million fund will target 10 to 12 early-stage preclinical companies with Series A rounds in the $20 million to $40 million range with opportunities for Series B follow-ups. The oversubscribed fund is bringing the band back with initial investors from PXVI as well as new investors that include “top-tier” asset managers, endowments, foundations, family offices, and individual investors.

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A clos­er look at the FDA’s more than 700 pan­dem­ic-re­lat­ed record re­quests to re­place on­site in­spec­tions

As the pandemic constrained the FDA’s ability to travel for onsite manufacturing inspections, the agency increasingly turned to requesting records to fill the gap, even for hundreds of US-based facilities.

FDA explains in its guidance on manufacturing inspections during the pandemic that the agency can request records (not to be confused with the FDA’s remote interactive evaluations) directly from facilities “in advance of or in lieu of” certain onsite inspections. Companies are legally required to fulfill those requests because a denial may be considered limiting an inspection, which could lead to the FDA deeming a drug made at that site to be adulterated.

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Stephen Squinto, Gennao Bio CEO (Gennao)

Alex­ion co-founder Stephen Squin­to is back in the game as CEO, this time for a small gene ther­a­py play­er

With his name already behind a rare disease success story in Alexion, Stephen Squinto was looking for a great story to drive him to jump back into the biotech game. He found that in a fledging non-viral gene therapy company, and now he’s got a few backers on board as well.

On Tuesday, Gennao Bio launched with a $40 million Series A co-led by OrbiMed and Logos Capital with participation by Surveyor Capital. The biotech, which is looking to use its cell-penetrating antibody platform to deliver nucleic acid “payloads” during into the nucleus, had to rush for its initial series — and had a name change along the way.

Alvotech takes Ab­b­Vie to court over al­leged patent 'mine­field' sur­round­ing megablock­buster Hu­mi­ra

AbbVie has so far been successful in shooing away competition to its megablockbuster Humira, deploying a number of patents and settlements to keep biosimilars off the US market until 2023. But one Icelandic drugmaker doesn’t want to wait — and on Tuesday, it filed a lawsuit challenging what it called a patent “minefield.”

Alvotech has accused AbbVie of trying to “overwhelm” and “intimidate” it with “an outrageous number of patents of dubious validity,” according to court documents. The company is currently seeking approval for its Humira copycat AVT02, which AbbVie says would infringe upon 62 patents.