#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.


Fangliang Zhang, AP Images

Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

Mer­ck wins a third FDA nod for an­tibi­ot­ic; Mereo tack­les TIG­IT with $70M raise in hand

Merck — one of the last big pharma bastions in the beleaguered field of antibiotic drug development — on Friday said the FDA had signed off on using its combination drug, Recarbrio, with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. The drug could come handy for use in hospitalized patients who are afflicted with Covid-19, who carry a higher risk of contracting secondary bacterial infections. Once SARS-CoV-2, the virus behind Covid-19, infects the airways, it engages the immune system, giving other pathogens free rein to pillage and plunder as they please — the issue is particularly pertinent in patients on ventilators, which in any case are breeding grounds for infectious bacteria.

President Donald Trump (left) and Moncef Slaoui, head of Operation Warp Speed (Alex Brandon, AP Images)

UP­DAT­ED: White House names fi­nal­ists for Op­er­a­tion Warp Speed — with 5 ex­pect­ed names and one no­table omis­sion

A month after word first broke of the Trump Administration’s plan to rapidly accelerate the development and production of a Covid-19 vaccine, the White House has selected the five vaccine candidates they consider most likely to succeed, The New York Times reported.

Most of the names in the plan, known as Operation Warp Speed, will come as little surprise to those who have watched the last four months of vaccine developments: Moderna, which was the first vaccine to reach humans and is now the furthest along of any US effort; J&J, which has not gone into trials but received around $500 million in funding from BARDA earlier this year; the joint AstraZeneca-Oxford venture which was granted $1.2 billion from BARDA two weeks ago; Pfizer, which has been working with the mRNA biotech BioNTech; and Merck, which just entered the race and expects to put their two vaccine candidates into humans later this year.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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RA Cap­i­tal, Hill­house join $310M rush to back Ever­est's climb to com­mer­cial heights in Chi­na

Money has never been an issue for Everest Medicines. With an essentially open tab from their founders at C-Bridge Capital, the biotech has gone two and a half years racking up drug after drug, bringing in top exec after top exec, and issuing clinical update after update.

But now other investors want in — and they’re betting big.

Everest is closing its Series C at $310 million. The first $50 million comes from the Jiashan National Economic and Technological Development Zone; the remaining C-2 tranche was led by Janchor Partners, with RA Capital Management and Hillhouse Capital as co-leaders. Decheng Capital, GT Fund, Janus Henderson Investors, Rock Springs Capital, Octagon Investments all joined.

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

David Meline (file photo)

Mod­er­na’s new CFO took a cut in salary to jump to the mR­NA rev­o­lu­tion­ary. But then there’s the rest of the com­pen­sa­tion pack­age

David Meline took a little off the top of his salary when he jumped from the CFO post at giant Amgen to become the numbers czar at the upstart vaccines revolutionary Moderna. But the SEC filing that goes with a major hire also illustrates how it puts him in line for a fortune — provided the biotech player makes good as a promising game changer.

To be sure, there’s nothing wrong with the base salary: $600,000. Or the up-to 50% annual cash bonus — an industry standard — that comes with it. True, the 62-year-old earned $999,000 at Amgen in 2019, but it’s the stock options that really count in the current market bliss for all things biopharma. And there Meline did well.

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