UP­DAT­ED: Take­da suc­ceeds where oth­er phar­mas have failed with PhI­II win for cy­tomegalovirus castoff marib­avir

Marib­avir, once a tri­al dud and mul­ti­ple-time castoff, re­ceived new life from the FDA right be­fore Take­da picked up Shire in 2019. Now, Take­da is post­ing win­ning late-stage da­ta from the drug that could help it suc­ceed where so many oth­ers have failed.

In a 352-per­son tri­al com­par­ing marib­avir to physi­cian’s choice an­tivi­rals, more than twice as many pa­tients on marib­avir achieved CMV viremia clear­ance at eight weeks — the study’s pri­ma­ry end­point, ac­cord­ing to Take­da. Of the 235 pa­tients who re­ceived marib­avir, 131 (or 55.7%) achieved clear­ance ver­sus 28 of 117 (or 23.9%) of those on con­ven­tion­al an­tivi­ral ther­a­pies (p<0.001). Viremia is the iso­la­tion of CMV by cul­ture.

CMV, or cy­tomegalovirus, is a com­mon virus that af­fects much of the pop­u­la­tion with­out caus­ing symp­toms, but it can be dan­ger­ous to peo­ple with com­pro­mised im­mune sys­tems, in­clud­ing re­cip­i­ents of bone mar­row or or­gan trans­plants.

Vol­un­teers in Take­da’s open-la­bel tri­al, dubbed SOL­STICE, ran­dom­ly re­ceived ei­ther marib­avir, or one or a com­bi­na­tion of com­mon­ly used an­tivi­ral ther­a­pies like gan­ci­clovir, val­gan­ci­clovir, fos­car­net or cid­o­fovir. The par­tic­i­pants, who were hematopoi­et­ic cell trans­plant and sol­id or­gan trans­plant re­cip­i­ents, were treat­ed for eight weeks, then fol­lowed for an­oth­er 12.

Break­ing it down fur­ther, Take­da said 55.6% of sol­id or­gan trans­plant pa­tients on marib­avir saw CMV viremia clear­ance at week eight, com­pared with 26.1% of those on oth­er ther­a­pies. And of the hematopoi­et­ic cell trans­plant pa­tients, 55.9% achieved clear­ance at week eight com­pared to 20.8% on oth­er drugs.

In ad­di­tion to the pri­ma­ry end­point, Take­da says it met a key sec­ondary end­point: im­prove­ment in the clear­ance of CMV viremia and as­so­ci­at­ed symp­tom con­trol through four months And those who took marib­avir showed a low­er in­ci­dence of treat­ment-re­lat­ed tox­i­c­i­ties com­mon with oth­er an­tivi­rals, ac­cord­ing to the com­pa­ny.

Treat­ment-re­lat­ed se­ri­ous ad­verse events led to the deaths of one pa­tient in each treat­ment group, ac­cord­ing to Take­da, though it’s un­clear what caused the deaths. As of press time, the com­pa­ny de­clined to pro­vide more in­for­ma­tion.

Take­da of­fered a first glimpse at the Phase III re­sults back in De­cem­ber, and an­nounced that it would take the da­ta to reg­u­la­tors in the US and Eu­rope. In an emailed state­ment, Take­da said it plans to file with the FDA in the first half of FY 2021.

An ap­proval would be a sweet end to marib­avir’s wild-two-decade ride. Glax­o­SmithK­line first syn­the­sized the drug 20 years ago and did some ear­ly clin­i­cal work, be­fore li­cens­ing it to the rare dis­ease and in­fec­tious dis­ease-fo­cused biotech Vi­roPhar­ma.

Vi­roPhar­ma suc­cess­ful­ly took it through Phase II, then missed the pri­ma­ry end­point in a Phase III study in 2009. Marib­avir failed to pre­vent CMV in­fec­tions bet­ter than place­bo in pa­tients re­ceiv­ing bone mar­row trans­plants. Vi­roPhar­ma sug­gest­ed a high­er dose might lead to a bet­ter re­sponse — but end­ed up pass­ing the can­di­date to Shire dur­ing a $4.2 bil­lion buy­out in 2013.

Shire ran with Vi­roPhar­ma’s idea, giv­ing 4 to 12 times more drug in var­i­ous phar­ma­co­ki­net­ic and ef­fi­ca­cy stud­ies. They got the re­sults they were look­ing for in 2016, prov­ing in a Phase II study that 400mg, 800mg, and 1200mg helped clear in­fec­tion. The FDA com­mend­ed the re­sults with a break­through des­ig­na­tion in 2018. And the fol­low­ing year, Take­da com­plet­ed its ac­qui­si­tion of Shire for $62 bil­lion.

Marib­avir has come a long way in­deed, but it’s not over the goal line just yet.

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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Eli Lil­ly claims a TKO in its long-run­ning ti­tle fight with No­vo Nordisk for the block­buster di­a­betes mar­ket — but there’s a hitch

Eli Lilly isn’t just gunning for a better diabetes drug in tirzepatide. They want to cut ahead of Novo Nordisk’s blockbuster rival Ozempic (semaglutide) on the obesity front as well. But a newly-claimed win in a head-to-head Phase III showdown over reducing A1C while shedding pounds — complete with clear evidence of superiority over the approved rival — could prove a tough sell right now.

Let’s start with the latest data from Lilly.

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Hal Barron, Endpoints UKBIO19

GSK, Vir's hopes for a Covid-19 an­ti­body fall flat in NIH 'mas­ter pro­to­col' with no ben­e­fit in hos­pi­tal­ized pa­tients

GlaxoSmithKline and Vir Biotechnology were hopeful that one of their partnered antibodies would carve out a win after getting the invite to a major NIH study in hospitalized Covid-19 patients. But just like Eli Lilly, the pair’s drug couldn’t hit the mark, and now they’ll be left to take a hard look at the game plan.

The NIH has shut down enrollment for GSK and Vir’s antibody VIR-7831 in its late-stage ACTIV-3 trial after the drug showed negligible effect in achieving sustained recovery in hospitalized Covid-19 patients, the partners said Wednesday.

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Eli Lil­ly claims suc­cess in a new JAK in­di­ca­tion: hair loss

Over the last decade, drugmakers have proven JAK inhibitors can treat a smattering of immune-related diseases ranging from rheumatoid arthritis to Covid-19. Now Eli Lilly has pulled out a new one.

Lilly and its biotech partner Incyte announced Wednesday that their JAK inhibitor baricitinib effectively regrew patients’ hair in a Phase III trial for alopecia areata, an autoimmune condition that can cause sudden, severe and patchy hair loss. Lilly didn’t break down the results from the 546-patient trial, but the primary endpoint was improvement on a standard score for alopecia symptoms.

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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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