FDA fol­lows through with a ground­break­ing OK for Yescar­ta, Gilead­'s new CAR-T break­through

Just two weeks af­ter Gilead closed on its $12 bil­lion Kite buy­out, the FDA has fol­lowed through with a ground­break­ing ap­proval of Yescar­ta (axi-cel), putting its CAR-T drug neck-and-neck with No­var­tis’ pi­o­neer Kym­ri­ah as the two drugs are prepped for a launch.

In a vir­tu­al heart­beat, Gilead used its con­sid­er­able cash re­serves to reach a deal to buy out Kite and axi-cel 6 weeks ago, ac­quir­ing its new­ly ap­proved CAR-T and all the next-gen tech­nol­o­gy now in the works. The ac­qui­si­tion made Gilead an overnight leader in CAR-T. While beat­en to a his­toric first FDA ap­proval for a CAR-T by an ag­gres­sive group at No­var­tis — ini­tial­ly green-light­ed at the end of Au­gust for pe­di­atric and young adult pa­tients with a form of acute lym­phoblas­tic leukemia — Gilead is re­tain­ing most of the Kite gang and hon­ing its man­u­fac­tur­ing ef­fort, shav­ing off the time it takes to turn around these per­son­al­ized ther­a­pies.

In clas­sic ag­gres­sive form, Gilead came out gun­ning, of­fer­ing the ther­a­py at a price of $373,000 — $102,000 less than its ri­val at No­var­tis. On the oth­er hand, No­var­tis of­fered a val­ue-based deal to a num­ber of pay­ers in which they on­ly get re­im­burse­ment for pa­tients who re­spond to ther­a­py, evening the play­ing field.

Once again, FDA com­mis­sion­er Scott Got­tlieb took the hon­ors in con­grat­u­lat­ing the de­vel­op­ers, as he did when No­var­tis came out in front. And this time, he promised to lend the agency’s help for the rest of the bur­geon­ing cell ther­a­py field. Said Got­tlieb:

“To­day marks an­oth­er mile­stone in the de­vel­op­ment of a whole new sci­en­tif­ic par­a­digm for the treat­ment of se­ri­ous dis­eases. In just sev­er­al decades, gene ther­a­py has gone from be­ing a promis­ing con­cept to a prac­ti­cal so­lu­tion to dead­ly and large­ly un­treat­able forms of can­cer. This ap­proval demon­strates the con­tin­ued mo­men­tum of this promis­ing new area of med­i­cine and we’re com­mit­ted to sup­port­ing and help­ing ex­pe­dite the de­vel­op­ment of these prod­ucts. We will soon re­lease a com­pre­hen­sive pol­i­cy to ad­dress how we plan to sup­port the de­vel­op­ment of cell-based re­gen­er­a­tive med­i­cine. That pol­i­cy will al­so clar­i­fy how we will ap­ply our ex­pe­dit­ed pro­grams to break­through prod­ucts that use CAR-T cells and oth­er gene ther­a­pies. We re­main com­mit­ted to sup­port­ing the ef­fi­cient de­vel­op­ment of safe and ef­fec­tive treat­ments that lever­age these new sci­en­tif­ic plat­forms.”

The CD19 T cell im­munother­a­py — which reengi­neers pa­tient cells in­to a po­tent can­cer ther­a­py — has been ap­proved for adult pa­tients with re­lapsed or re­frac­to­ry large B-cell lym­phoma af­ter two or more lines of sys­temic ther­a­py. That la­bel in­cludes dif­fuse large B-cell lym­phoma (DL­B­CL), pri­ma­ry me­di­asti­nal large B-cell lym­phoma, high-grade B-cell lym­phoma, and DL­B­CL aris­ing from fol­lic­u­lar lym­phoma.

Alessan­dro Ri­va

The R&D work will now be led by Alessan­dro Ri­va, a for­mer No­var­tis sci­en­tist pro­mot­ed yes­ter­day to ex­ec­u­tive vice pres­i­dent in charge of on­col­o­gy R&D, with a seat on the lead­er­ship team.

Left be­hind in the race to CAR-T dom­i­nance, for now at least, is Juno Ther­a­peu­tics. Its ri­val drug was mired down by a lethal tox­i­c­i­ty is­sue that killed 5 pa­tients, forc­ing the biotech to switch over to its num­ber 2 pro­gram.

No­var­tis man­aged to sur­prise quite a few an­a­lysts by peg­ging Kym­ri­ah at $475,000, which is sig­nif­i­cant­ly low­er than the $600,000 max­i­mum pro­vid­ed in some of the spreads. In a sto­ry we pub­lished yes­ter­day, how­ev­er, a num­ber of ex­perts said the full cost of ther­a­py may well end up at $1 mil­lion to $1.5 mil­lion.

The da­ta, though, are jaw drop­ping.

The FDA’s ap­proval comes through on the da­ta for ZU­MA-1, which demon­strat­ed that 72% of the pa­tients in­volved had an ob­jec­tive re­sponse rate to the ther­a­py. And 51% demon­strat­ed a com­plete re­mis­sion, with no sign of the can­cer left.

In a re­cent farewell let­ter to the staff, Kite CEO Arie Bellde­grun summed it up by writ­ing:

In a span of just a few short years, we grew from few­er than 10 em­ploy­ees to al­most 700. The com­pa­ny’s val­ue in­creased 2300% from the time of our IPO to near­ly $12 bil­lion with the ac­qui­si­tion by Gilead Sci­ences. Our clos­ing $180 per share price rep­re­sents not just a 960% ap­pre­ci­a­tion from the IPO price of $17 per share, but the largest ever pre-com­mer­cial bio­phar­ma ac­qui­si­tion.

Now Gilead can see if it’s ag­gres­sive team can make the most of the block­buster peak sales es­ti­mates that have yet to be climbed.

To­day, Bellde­grun had this to say:

“The FDA ap­proval of Yescar­ta is a land­mark for pa­tients with re­lapsed or re­frac­to­ry large B-cell lym­phoma. This ap­proval would not have been pos­si­ble with­out the coura­geous com­mit­ment of pa­tients and clin­i­cians, as well as the on­go­ing ded­i­ca­tion of Kite’s em­ploy­ees. We must al­so rec­og­nize the FDA for their abil­i­ty to em­brace and sup­port trans­for­ma­tion­al new tech­nolo­gies that treat life-threat­en­ing ill­ness­es. We be­lieve this is on­ly the be­gin­ning for CAR T ther­a­pies.”

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.

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When Regeneron scored an early approval for lipid lowering antibody Evkeeza back in February, the drugmaker cracked open a new pathway to lower abnormally high cholesterol levels. Now, Regeneron is chasing high triglycerides as well with some promising mid-stage data — but will genetic restrictions limit the drug’s use?

Regeneron’s Evkeeza (evinacumab) cut median triglyceride levels by more than 800 mg/dL (57%) in patients with a rare disorder causing abnormally high triglyceride levels compared with an overall increase of 50 mg/dL (1.8%) in participants on placebo, according to Phase II data presented Sunday at the virtual American College of Cardiology meeting.

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I still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

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As­traZeneca's Farx­i­ga missed big on Covid-19 study, but it's tak­ing SGLT2 safe­ty da­ta as a sil­ver lin­ing

AstraZeneca hasn’t seen many setbacks in recent months for SGLT2 inhibitor Farxiga, which broke ground in heart failure and kidney disease regardless of diabetes diagnosis. But the British drugmaker had to admit defeat in taking Farxiga into Covid-19, but follow-up results add a bit of a silver lining to that trial’s safety data.

Of hospitalized Covid-19 patients dosed with AstraZeneca’s Farxiga, 11.2% experienced an organ failure or died after 30 days of therapy compared with 13.8% of those given placebo, according to follow-up data from the DARE-19 study revealed Sunday at the virtual American College of Cardiology meeting.

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Pfizer and Bristol Myers Squibb’s non-warfarin blood thinner Eliquis has raced out to become the most prescribed drug of its class on the market — even overtaking warfarin’s long-time lead. But in tricky-to-treat patients after a valve replacement, an investigator-sponsored study couldn’t turn up benefit and raised a troubling safety signal.

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No­var­tis whiffs on En­tresto study af­ter heart at­tacks — but that does­n't mean it's go­ing down qui­et­ly

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Michael Dell (Richard Drew, AP Images)

'Dude, you're get­ting a Del­l' — as a new deep-pock­et biotech in­vestor

What happens when you marry longtime insiders in the global biotech VC game with the family fund of tech billionaire Michael Dell, a synthetic biology legend out of MIT and Harvard and the former director of the NCI?

Today, the answer is a newly financed, $200 million biotech SPAC now cruising the industry for a top player interested in finding a short cut to Nasdaq.

Orion Biotech Opportunities priced their blank check company today, raising $200 million with Dell’s multibillion-dollar MSD group’s commitment on investing another $20 million in a forward-purchase agreement.

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Gene ther­a­py from Bio­gen's $800M buy­out flops in mid-stage study, deal­ing blow to new am­bi­tions

The #2 candidate from Biogen’s $800 million ocular gene therapy buyout has failed in a mid-stage trial, dealing an early blow to the big biotech’s plans to revitalize its pipeline with new technologies.

Biogen announced that the candidate, an experimental treatment for a rare and progressive form of blindness called X-linked retinitis pigmentosa (XLRP), failed to sufficiently improve vision in patients’ treated eye — patients only received an injection in one eye — after a year, on a standard scale, compared to their untreated eye. The company said they saw “positive trends” on several secondary endpoints, including visual acuity, but declined to say whether the trial actually hit any of those endpoints.

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In­cyte’s PD-(L)1 in­hibitor head­ed for an ODAC show­down next month

The FDA’s Oncologic Drugs Advisory Committee will spend a half day on June 24 reviewing Incyte’s PD-(L)1 inhibitor retifanlimab as a treatment for locally advanced or metastatic squamous carcinoma of the anal canal (SCAC) for those who have progressed on or who are intolerant of platinum-based chemotherapy.

The eighth PD-(L)1 entrant in January nabbed a priority review and an orphan designation from the FDA, which sets the agency’s final decision date as July 25.