Astel­las, Seagen pave the way for Pad­cev's glob­al roll­out with full con­fir­ma­to­ry da­ta for urothe­lial can­cer in hand

Astel­las and Seagen made a big splash with their Nectin-4 tar­get­ing ther­a­py Pad­cev in late 2019, scor­ing a con­di­tion­al FDA ap­proval to tar­get urothe­lial can­cer. Now, the re­sults are in for the con­fir­ma­to­ry study for that in­di­ca­tion, and it looks like a re­sound­ing win for Pad­cev.

Astel­las and Seagen’s Pad­cev ex­tend­ed pa­tients’ lives to an av­er­age 12.9 months com­pared with nine months for a chemo con­trol, ac­cord­ing to full da­ta from the Phase III EV-301 study pre­sent­ed Fri­day at the vir­tu­al AS­CO GU meet­ing.

Re­sults from the EV-301 tri­al showed Pad­cev ad­min­is­tered af­ter plat­inum-based chemo and a pri­or PD-1 ther­a­py sig­nif­i­cant­ly ex­tend­ed OS, with a sparkling p-val­ue of 0.001. On the study’s sec­ondary end­points, Pad­cev al­so sig­nif­i­cant­ly boost­ed pro­gres­sion-free sur­vival, over­all re­sponse rate and dis­ease con­trol rate over chemo. Me­di­an PFS was 5.6 months for the Pad­cev arm com­pared with 3.7 months for the chemo con­trol.

Top-line da­ta from EV-301 was un­veiled back in Sep­tem­ber and showed a 30% re­duc­tion in risk of death (p = 0.001) and 39% re­duc­tion in risk of dis­ease pro­gres­sion or death (p<0.00001). The lat­est da­ta was joint­ly pub­lished Fri­day in the New Eng­land Jour­nal of Med­i­cine.

With the full con­fir­ma­to­ry da­ta in hand, the part­ners are aim­ing to file for a com­plete FDA ap­proval by the end of March and then roll out sub­mis­sions in­to tar­get­ed mar­kets around the globe, the com­pa­ny said in a re­lease. Pad­cev, an an­ti­body-drug con­ju­gate, cur­rent­ly sports an ac­cel­er­at­ed ap­proval from the FDA as the first ther­a­py of its kind to tar­get the Nectin-4 pro­tein.

Back­ing those sub­mis­sions are da­ta from a sec­ond co­hort in the Phase II EV-102 tri­al, which were al­so un­veiled Fri­day. In the sec­ond half of the sin­gle-arm EV-201 — the first half was used as the ba­sis for the FDA’s ac­cel­er­at­ed ap­proval in De­cem­ber 2019 — Pad­cev was test­ed on urothe­lial can­cer pa­tients who had re­ceived a pri­or PD-1/L-1 in­hibitor but who had not re­ceived pri­or plat­inum-based chemo and were in­el­i­gi­ble for cis­platin due to pre­ex­ist­ing co-mor­bidi­ties.

In that set­ting, 52% of pa­tients who re­ceived Pad­cev had an ob­jec­tive re­sponse with a me­di­an du­ra­tion of re­sponse of 10.9 months.  Twen­ty per­cent of Pad­cev pa­tients had a com­plete re­sponse, and 31% had a par­tial re­sponse. The part­ners plan to sub­mit EV-201 as part of their FDA ap­pli­ca­tion in March and will pick and choose where to sub­mit those da­ta for glob­al reg­u­la­to­ry re­views.

Andy Krivoshik

In EV-201, 17% of all Grade 3 side ef­fects were skin re­ac­tions, which will lead Astel­las and Seagen to pen a “Dear HCP” let­ter as part of an ef­fort to up­date pre­scrib­ing in­for­ma­tion on the ther­a­py, said Andy Krivoshik, an Astel­las se­nior VP and head of the on­col­o­gy ther­a­peu­tic area. Pad­cev’s la­bel in­cludes a warn­ing for skin re­ac­tions, cit­ing 54% of pa­tients in the piv­otal tri­al showed a skin re­ac­tion to treat­ment.

“Even though Nectin-4 is known to be ex­pressed in the skin and is called out in the US­PI, as we’re work­ing with reg­u­la­tors we want to make sure this is some­thing that’s called out to pre­scribers in par­tic­u­lar,” he told End­points News.

Af­ter fol­low­ing through in late-stage urothe­lial can­cer, Krivoshik said the teams at Astel­las and Seagen are look­ing for op­por­tu­ni­ties to take Pad­cev in­to ear­ly stages of the dis­ease as well as in oth­er tu­mor types with high Nectin-4 ex­pres­sion.

One of those ear­ly-stage ef­forts — a com­bo study along­side PD-(L)1 in­hibitor Keytru­da from Mer­ck — could even­tu­al­ly bear fruit and build a case for the ADC class on the whole in ear­li­er set­tings. Ul­ti­mate­ly, how­ev­er, the part­ners are most fo­cused on break­ing ground for un­der­served pa­tients, Krivoshik said.

“We re­al­ly look for ar­eas where there are high un­met need,” he said.

Ed­i­tor’s Note: This sto­ry has been up­dat­ed to cor­rect an er­ror. Astel­las and Seagen’s “Dear HCP” let­ter is not tied to its FDA sub­mis­sion pack­et. 

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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