Re­gen­eron an­ti­body earns nod for rare cho­les­terol dis­or­der — but it ain't cheap

Re­gen­eron has a new ap­proved drug to add to its sta­ble of mon­o­clon­al an­ti­bod­ies.

The FDA gave the thumbs-up to the biotech’s evinacum­ab, to be called Evkeeza, as a sup­ple­ment to oth­er LDL-low­er­ing treat­ments for the rare ge­net­ic dis­or­der ho­mozy­gous fa­mil­ial hy­per­c­ho­les­terolemia. Evkeeza has been in­di­cat­ed for pa­tients old­er than 12 and is priced based on weight, but Re­gen­eron ex­pects it will cost an av­er­age of $450,000 per year.

HoFH is part of a fam­i­ly of dis­or­ders that af­fect the body’s abil­i­ty to break down LDL cho­les­terol, Evkeeza tri­al clin­i­cian and car­di­ol­o­gist Seth Baum told End­points News. Doc­tors be­lieve the dis­ease af­fects about 1,300 pa­tients in the US, but Baum said it’s dif­fi­cult to know the ex­act num­ber be­cause for years the dis­ease was not thought to be dif­fer­ent from its cousin, het­erozy­gous fa­mil­ial hy­per­c­ho­les­terolemia.

Where­as pa­tients with the het­erozy­gous form of the dis­or­der on­ly need the mal­func­tion­ing gene from one par­ent, ho­mozy­gous pa­tients get the mu­ta­tion from both. In many HoFH pa­tients, typ­i­cal cho­les­terol-low­er­ing treat­ments like statins and PC­SK9 in­hibitors are es­sen­tial­ly use­less, and in the most dif­fi­cult to treat pop­u­la­tion — called “null/null” — LDL re­cep­tors in the liv­er bare­ly func­tion at all.

That usu­al­ly leads to LDL cho­les­terol lev­els in the range of 400 to 500 mg/dL, with the lev­els some­times reach­ing 1,000. The av­er­age Amer­i­can, mean­while, has LDL lev­els of 112 mg/dL, Baum said, mean­ing HoFH pa­tients can be high­ly sus­cep­ti­ble to pre­ma­ture heart dis­ease be­fore the age of 10.

Evkeeza is not in­di­cat­ed for in­di­vid­u­als with het­erozy­gous fa­mil­ial hy­per­c­ho­les­terolemia, and the ef­fect of Evkeeza on car­dio­vas­cu­lar mor­bid­i­ty and mor­tal­i­ty has not been de­ter­mined. The drug works by block­ing the func­tion of an­giopoi­etin-like 3, a pro­tein that plays a key role in lipid me­tab­o­lism. Re­gen­eron says it’s the first FDA-ap­proved med­ica­tion to block this pro­tein.

In Re­gen­eron’s piv­otal study up­on which Thurs­day’s ap­proval is based, the com­pa­ny en­rolled 65 pa­tients who were al­ready on max­i­mal­ly tol­er­at­ed lipid-low­er­ing ther­a­pies. These in­di­vid­u­als had failed on all oth­er ther­a­pies, and were ran­dom­ized 2-to-1 to the drug arm.

Pa­tients tak­ing Evkeeza saw a 47% re­duc­tion in LDL lev­els from base­line, com­pared to a 2% in­crease in the con­trol. The drug arm al­so saw sig­nif­i­cant re­duc­tions in lev­els of apolipopro­tein B, an in­di­ca­tor of vas­cu­lar dis­ease, as well as triglyc­erides and over­all cho­les­terol.

The most com­mon side ef­fects that oc­curred more of­ten in the Evkeeza arm were in­ci­dents of the com­mon cold, flu-like ill­ness, dizzi­ness and run­ny nose. Dur­ing the dou­ble-blind­ed por­tion of the tri­al, 66% of evinacum­ab pa­tients and 81% of place­bo pa­tients ex­pe­ri­enced at least one ad­verse event.

It’s an­oth­er weapon for Re­gen­eron in the cho­les­terol are­na, which al­ready has an ap­proved PC­SK9 in­hibitor in Pralu­ent. Orig­i­nal­ly OK’ed back in 2015, Pralu­ent saw a low­er-than-ex­pect­ed up­take af­ter the ini­tial price re­sult­ed in some stick­er shock. Pralu­ent and Am­gen’s Repatha, the oth­er big PC­SK9 drug on the mar­ket, en­gaged in a spar­ring match with in­sur­ers as a re­sult — their prices were slashed to $5,850 in Oc­to­ber 2018 af­ter in­sur­ers won that bat­tle. But PC­SK9 drugs aren’t the on­ly cho­les­terol-low­er­ing meds out here, as Es­pe­ri­on re­cent­ly launched Nexl­izet as a once-dai­ly pill and a cheap­er op­tion to the an­ti­bod­ies.

Evkeeza is al­so the next in a long line of an­ti­body treat­ments that have come from Re­gen­eron’s ge­net­i­cal­ly-en­gi­neered mouse plat­form, a list that in­cludes Pralu­ent, Kevzara, Lib­tayo and the block­buster Dupix­ent. Those four drugs pulled in near­ly $4 bil­lion for the biotech in 2020, though the vast ma­jor­i­ty came from Dupix­ent sales.

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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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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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.