Bris­tol My­ers Squibb earns long-await­ed FDA nod for liso-cel, join­ing short list of lym­phoma CAR-T win­ners

When Bris­tol My­ers Squibb bought out Cel­gene for $74 bil­lion back in late 2019, one of the pur­port­ed cen­ter­pieces in that deal was liso-cel, which hoped to join a small group of CAR-Ts for non-Hodgkin lym­phoma. Ex­pect­ing an ap­proval in 2020, Bris­tol has had its share of set­backs in get­ting liso-cel across the fin­ish line — but now it fi­nal­ly has the green light.

The FDA on Fri­day ap­proved Bris­tol’s Breyanzi (liso­cab­ta­gene mar­aleu­cel), a CAR-T to treat dif­fuse large B cell lym­phoma in pa­tients who have pre­vi­ous­ly re­ceived two pri­or rounds of sys­temic ther­a­py, the agency said in a re­lease.

The agency based its re­view on piv­otal Phase I da­ta show­ing 54% of pa­tients treat­ed with liso-cel achieve com­plete re­mis­sion. DL­B­CL makes up about 33% of all non-Hodgkin lym­phoma cas­es, the FDA said, of which there are around 77,000 new­ly di­ag­nosed each year.

The one-time ther­a­py will come with a $410,300 whole­sale price, Bris­tol said, say­ing it came up with that fig­ure af­ter con­sid­er­ing “many fac­tors in­clud­ing its med­ical and clin­i­cal val­ue, pa­tient val­ue and so­ci­etal val­ue.”

That’s a sig­nif­i­cant pre­mi­um over Gilead’s Yescar­ta, which launched with a $373,000. Kym­ri­ah al­so launched with a $373,000 WAC for B cell lym­phomas.

With the ap­proval will come a black-box warn­ing la­bel for both cy­tokine re­lease syn­drome, a po­ten­tial­ly fa­tal over­re­ac­tion of the im­mune sys­tem, as well as neu­ro­log­ic tox­i­c­i­ties. Those warn­ings are se­vere enough that the FDA has in­sti­tut­ed a Risk Eval­u­a­tion and Mit­i­ga­tion Strat­e­gy that will re­quire health­care fa­cil­i­ties and physi­cians ad­min­is­ter­ing the ther­a­py to be spe­cial­ly cer­ti­fied to iden­ti­fy and treat CRS and neu­ro tox­i­c­i­ties.

Those warn­ings and ad­min­is­tra­tion re­stric­tions are aren’t unique to liso-cel, how­ev­er. Yescar­ta and Kym­ri­ah, for in­stance, sport the same black box warn­ings, and the un­met clin­i­cal need will like­ly dri­ve up­take in what is an ex­treme­ly dif­fi­cult-to-treat pa­tient pop­u­la­tion.

Liso-cel is now the third CAR-T on the mar­ket for var­i­ous forms of non-Hodgkin lym­phoma, along­side Yescar­ta and Kym­ri­ah. Bris­tol aimed to have the ther­a­py ap­proved late last year, but de­lays from Covid-19 and an ug­ly in­spec­tion re­port at one of the com­pa­ny’s con­tract man­u­fac­tur­ing sites pushed the ap­proval in­to the new year.

Liso-cel was one of a group of pipeline can­di­dates tied to a $9 CVR from Bris­tol’s Cel­gene buy­out in 2019. With the ap­proval de­lay, in­vestors lost out on that pay­day when the year ex­pired — not a ma­jor is­sue for Bris­tol it­self but def­i­nite­ly a headache for the CVR traders.

In De­cem­ber, an FDA in­spec­tion at Lon­za Hous­ton’s plant found a raft of is­sues, in­clud­ing mis­la­bel­ing, prod­ucts for the US and EU drug mar­kets stored in the same bins, “poor­ly main­tained” freez­er units, and ex­pired batch­es of in­gre­di­ents that weren’t prop­er­ly dis­posed of, ac­cord­ing to a Form 483 let­ter pub­lished on­line late last month.

Lon­za, one of a group of con­trac­tors work­ing on liso-cel’s man­u­fac­tur­ing, said de­lays in the FDA’s in­spec­tion sched­ule made it dif­fi­cult to ad­just in time for an ap­proval with­in 2020. Bris­tol pre­vi­ous­ly said it re­spond­ed to the agency’s con­cerns with­in eight days of re­ceiv­ing its let­ter.

The top 100 bio­phar­ma VCs, Bob Brad­way places $2B bet in can­cer, gene edit­ing pi­o­neer's new big idea, and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Before diving in, we had some news to share: Endpoints is launching a premium weekly report focusing on all things regulatory. Coverage will be led by our new senior editor, Zachary Brennan, who joins us from POLITICO. Arsalan Arif has more details in his Publisher’s Note.

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Robert Bradway (Photographer: Scott Eisen/Bloomberg via Getty Images)

UP­DAT­ED: Am­gen snaps up can­cer drug play­er Five Prime, adding PhI­II-ready FGFR2b drug in $2B M&A play

Amgen is making a long-awaited move on the M&A side, buying South San Francisco-based Five Prime $FPRX for close to $2 billion and adding a slate of new cancer drugs to the pipeline.

Amgen is paying $38 a share, putting the deal value at $1.9 billion. The stock closed at $21.26 last night, giving investors a 78% premium.

The jewel in the crown of this deal is bemarituzumab, which Amgen describes as a first-in-class, Phase III-ready anti-FGFR2b antibody. Amgen was drawn to the bargaining table by Five Prime’s mid-stage data on gastric cancer, satisfied by PFS and OS data helping to validate FGFR2b as a target. Amgen researchers will now expand on the R&D program in other epithelial cancers, including lung, breast, ovarian and other cancers.

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David Liu (Casey Atkins Photography courtesy Broad Institute)

David Liu has a new big idea: pro­teome edit­ing. It could one day shred tau, RAS and some of the worst dis­ease-caus­ing pro­teins

Before David Liu became famous for inventing new forms of gene editing, he was known around academia in part for a more obscure innovation: a Rube Goldberg-esque system that uses bacteria-infecting viruses to take one protein and turn it into another.

Since 2011, Liu’s lab has used the system, called PACE, to dream up fantastical new proteins: DNA base editors far more powerful than the original; more versatile forms of the gene editor Cas9; insecticides that kill insecticide-resistant bugs; enzymes that slide synthetic amino acids into living organisms. But they struggled throughout to master one of the most common and powerful proteins in the biological world: proteases, a set of Swiss army knife enzymes that cut, cleave or shred other proteins in everything from viruses to humans.

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The 2021 top 100 bio­phar­ma in­vestors: As the pan­dem­ic hit and IPOs boomed, VCs swung in­to ac­tion like nev­er be­fore

The global pandemic may have roiled economies, killed hundreds of thousands and throttled entire industries, but the only effect it had on biopharma venture investing was to help turbocharge the field to giddy new heights.

Below you’ll find the new top 100 venture investors in the industry, ranked by the number of deals they were publicly involved in, as tracked by DealForma chief Chris Dokomajilar. The numbers master then calculated the estimated amount of money they put into each deal — divvying up the cash by the number of players — to indicate how they managed their syndicates.

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CMO Levi Garraway (Genentech)

Fo­cus­ing on the bright side, FDA OKs Roche's Actem­ra for rare lung dis­ease de­spite PhI­II flop

Actemra’s failure to hit the primary endpoint in a Phase III study didn’t stop the FDA from granting Roche priority review. And it’s certainly not standing in the way of a sixth approval for Roche’s IL-6 drug.

Regulators have cleared Actemra, or tocilizumab, for systemic sclerosis-associated interstitial lung disease in adult patients. Roche’s big Genentech subsidiary notes that it is the first biologic approved for this rare disease.

As Brain­Storm con­tin­ues to tout ‘clear sig­nal’ on ALS drug, the FDA of­fers a rare pub­lic slap­down on the da­ta

A little more than a week after BrainStorm acknowledged that regulators at the FDA had informed them that the biotech needed more data before it could expect to gain an approval for its ALS treatment NurOwn — while still touting a “clear signal” of efficacy and not ruling out an application — the agency has decided to clarify the record in a most unusual statement.

The FDA statement amounts to a straight slapdown, offering a different set of efficacy numbers from the company’s public presentation last November and ruling out any chance of statistical significance.

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Bruce Cozadd, Jazz CEO (Jazz Pharmaceuticals)

Jazz CEO Bruce Cozadd cam­paigned for 6 months to buy GW Phar­ma. A 90% pre­mi­um sealed the deal — along with $17.6M in ‘re­ten­tion’ in­cen­tives

Jazz CEO Bruce Cozadd didn’t beat around the bush.

In his first video meeting with GW Pharma chief Justin Gover last July 8, he offered to pay $172 a share to get the company, which had beaten the odds in getting its remarkable cannabinoid drug Epidiolex across the regulatory finish line for epilepsy. GW’s stock closed at $129 that day.

Cozadd had already done his homework on the financing to make sure he could swing it the way he wanted. He just needed to do some due diligence before making the non-binding bid firm.

UP­DAT­ED: Not 3 weeks af­ter tak­ing Hu­ma­cyte pub­lic, Ra­jiv Shuk­la launch­es an­oth­er blank check com­pa­ny

One of biotech’s earliest SPAC investors is back with another blank-check company, less than a month after his last effort announced its intent to merge.

Rajiv Shukla is intending to take a third lucky winner public with Alpha Healthcare Acquisition III, filing to go public Thursday with a $150 million raise penciled in. The move comes just a couple of weeks after Shukla’s second SPAC said it would jump to Nasdaq in tandem with Laura Niklason’s Humacyte in a $255 million new investment.

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Paul Hudson, Getty Images

How does Paul Hud­son's $13.5M comp pack­age stack up against oth­er CEOs? He's in the 'first quar­tile'

Paul Hudson arrived at Sanofi like a hurricane, chopping off duds in the pipeline, shaking up the C-suite, striking big M&A deals and jumping into the Covid-19 vaccine race — all in an attempt to reboot a pharma giant notorious for its setbacks.

Now, we’re getting a look at what the CEO brought home in his first year on the job.

When all is said and done, Hudson will have made about $6.7 million in 2020, about $2.5 million of which has already been paid. The bigger figure includes a $2.3 million bonus that’s subject to approval at an April meeting, and another $1.8 million in variable compensation that has yet to be paid.

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