No­var­tis wins a key OK for Kym­ri­ah, but con­tin­u­ing man­u­fac­tur­ing woes hob­ble roll­out — ri­val Gilead CAR-T breaks in­to Eu­rope

No­var­tis CAR-T man­u­fac­tur­ing woes are con­tin­u­ing to put a crimp in its abil­i­ty to pro­vide ther­a­py to all po­ten­tial pa­tients.

Vas Narasimhan

The phar­ma gi­ant re­port­ed this morn­ing that the EC has stamped its ap­proval on mar­ket­ing Kym­ri­ah in Eu­rope for B-cell acute lym­phoblas­tic leukemia as well as treat­ment-re­sis­tant adults suf­fer­ing from dif­fuse large B-cell lym­phoma. But No­var­tis can on­ly make it avail­able to chil­dren with ALL now — adults will have to wait.

No­var­tis’s top ex­ecs have worked hard to smooth things over with an­a­lysts, but it’s been be­dev­iled by man­u­fac­tur­ing is­sues through­out the de­vel­op­ment stage and con­tin­ues to be af­fect­ed as it goes toe-to-toe with Gilead’s Kite, ap­proved for large B-cell lym­phoma. And Gilead is still com­ing on strong, not­ing this morn­ing that they re­ceived a Eu­ro­pean OK to mar­ket Yescar­ta for dif­fuse and pri­ma­ry me­di­asti­nal large B-cell lym­phoma.

A month ago No­var­tis CEO Vas Narasimhan not­ed dur­ing the Q2 call that:

I think it’s ear­ly days and we’ve al­ways said this is go­ing to be a five-year jour­ney with Kym­ri­ah to re­al­ly get us to be the glob­al­ly suc­cess­ful brand we want it to be.

On man­u­fac­tur­ing, we have seen some vari­abil­i­ty in our prod­uct spec­i­fi­ca­tions. This is some­thing we’re look­ing at now in DL­B­CL to make sure that we can con­tin­ue to ramp-up the de­mand. We feel con­fi­dent in the over­all longer-term out­look for Kym­ri­ah.

Liz Bar­rett

Liz Bar­rett, who runs No­var­tis on­col­o­gy, had this to say:

I think the most im­por­tant thing to let you know is that the vari­abil­i­ty that we’ve seen in the com­mer­cial spec­i­fi­ca­tions, which isn’t un­usu­al with a new ther­a­py as you launch in­to a new tar­get pa­tient pop­u­la­tion, is that we have still been able to de­liv­er fi­nal prod­uct to the ma­jor­i­ty of pa­tients.

As we’ve re­port­ed, though, the cell man­u­fac­tur­ing chief’s of­fice has been out­fit­ted with a re­volv­ing door at No­var­tis in re­cent years. Karen Walk­er left that post in ear­ly 2017, fol­lowed last spring by Spencer Fisk as he jumped ship to join the No­var­tis ex­ecs at Ru­bius. Those de­par­tures came on top of a ma­jor re­vamp for the cell and gene ther­a­py unit in 2016, which raised ques­tions at the time about No­var­tis’ abil­i­ty to keep up with Kite — though the phar­ma gi­ant wound up with the pi­o­neer­ing first OK. And No­var­tis’ is­sues with man­u­fac­tur­ing cell ther­a­pies ex­tend back to the sna­fus it ex­pe­ri­enced with late de­liv­ery to a small but sig­nif­i­cant group of pa­tients en­rolled in clin­i­cal tri­als.

At one stage in the de­vel­op­ment process, No­var­tis had a 6% fail­ure rate on the man­u­fac­tur­ing process in a key clin­i­cal tri­al, which they lat­er said was large­ly re­solved and brought down to 3%.

This morn­ing No­var­tis is fol­low­ing up with plans to in­vest €78.8 mil­lion in­to their cell and gene ther­a­py man­u­fac­tur­ing op­er­a­tions in Switzer­land in their lat­est stab at fix­ing the prob­lems.

But af­ter record­ing on­ly $16 mil­lion in sales for Q2, the big ques­tion loom­ing for No­var­tis is why pa­tients would want to take a risk with their ther­a­py if an­oth­er provider comes in­to the mar­ket which can do bet­ter on a com­plex task: ex­tract­ing T cells from pa­tients, mod­i­fy­ing them and then in­fus­ing pa­tients with a ther­a­peu­tic punch?

You can be sure that the top crew at Gilead and Kite — work­ing with a be­spoke man­u­fac­tur­ing site — are pay­ing close at­ten­tion.

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.

Re­gen­eron's Evkeeza shows promise in curb­ing high triglyc­erides, but will ge­net­ic dis­par­i­ties lim­it use?

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.

$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; and more

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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.

Vas Narasimhan (Photographer: Simon Dawson/Bloomberg via Getty Images)

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

If Novartis learned one thing from its interaction with the FDA over its latest heart failure approval for Entresto, it was that missing a primary endpoint may not be the nail in the coffin. Now, Entresto has missed again on a late-stage study in high-risk heart patients, and it’s already sowing the seeds for a path forward regardless.

Novartis’ Entresto couldn’t best standard-of-care ramipril in staving off a composite of deaths and heart failure events in patients with left ventricular systolic dysfunction and/or pulmonary congestion who have had a prior heart attack, according to topline data from the Phase III PARADISE-MI study revealed Saturday at the virtual American College of Cardiology meeting.

Pfiz­er, Bris­tol My­er­s' Eliquis flops in post-heart surgery pa­tients, spurring an 'un­ex­plained sig­nal' in cer­tain deaths

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.

Eliquis failed to show benefit over standard of care in preventing serious clinical outcomes after a transaortic valve replacement (TAVR) and was linked to an “unexplained signal” in a subset of populations with a higher rate of non-CV deaths who did not need blood thinners apart from the surgery, according to data presented Saturday at the virtual American College of Cardiology meeting.

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.