Amarin scores a big win for its car­dio out­comes study on Vas­cepa — stock races high­er as an­a­lysts ap­plaud

Amarin $AM­RN has staked its claim to the next big block­buster in the car­dio space, herald­ing a clear sta­tis­ti­cal win on the pri­ma­ry end­point for its 7-year clin­i­cal quest to prove that its in­dus­tri­al strength pu­ri­fied fish oil Vas­cepa can sig­nif­i­cant­ly re­duce ma­jor car­dio threats for a broad swath of pa­tients.

An ear­ly pre­view of the top-line da­ta rolled out at a bleary-eyed time in the morn­ing on Mon­day point­ed a di­rect ar­row at a rel­a­tive 25% drop in risk for ma­jor car­dio events — such as death, stroke and hos­pi­tal­iza­tion due to angi­na — hit­ting a high­ly sta­tis­ti­cal p=<0.001 for the pa­tients in the years-long RE­DUCE-IT study. And re­searchers al­so high-fived each oth­er for a clean safe­ty pro­file in the same head­line da­ta to make the state­ment.

The da­ta sup­port­ed “ro­bust” ev­i­dence of its ef­fect across mul­ti­ple sec­ondary end­points, ac­cord­ing to the com­pa­ny. We won’t see the par­tic­u­lars un­til lat­er, but the com­pa­ny is on track to file for ap­provals in ear­ly 2019.

An­a­lysts at Jef­feries have said that a suc­cess here could trans­form Vas­cepa in­to a $2 bil­lion-plus drug. And that num­ber res­onat­ed this morn­ing, as Amarin’s share prize zoomed up 288%. The stun­ning ad­vance fol­lowed fresh re­marks from Jef­feries about the rel­a­tive val­ue that Amarin un­der­scored this morn­ing rel­a­tive to oth­er drugs that have tried — and failed — to make much of an im­pres­sion.

The mag­ni­tude of MACE re­duc­tion is so far the great­est among all ther­a­pies on top of statins, far ex­ceed­ing the clin­i­cal­ly mean­ing­ful CV ben­e­fit ex­pec­ta­tion. Re­call two PC­SK9 in­hibitors (Repatha and Pralu­ent) and Ilaris all re­duced MACE risks by 15% in re­cent­ly com­plet­ed CVOTs (FOURI­ER, ODYSSEY, and CAN­TOS). The FDA has ex­pand­ed Repatha’s la­bel to in­clude cer­tain CV risk re­duc­tion and is cur­rent­ly re­view­ing sBLA of Pralu­ent in MACE re­duc­tion (PDU­FA on 4/28/19). Our doc sur­vey sug­gest­ed 10-15%+ risk re­duc­tion in MACE is con­sid­ered clin­i­cal­ly mean­ing­ful.

“We are de­light­ed with these topline study re­sults,” said John Thero, pres­i­dent and CEO of Amarin, in a state­ment. “Giv­en Vas­cepa is af­ford­ably priced, oral­ly ad­min­is­tered and has a fa­vor­able safe­ty pro­file, RE­DUCE-IT re­sults could lead to a new par­a­digm in treat­ment to fur­ther re­duce the sig­nif­i­cant car­dio­vas­cu­lar risk that re­mains in mil­lions of pa­tients with LDL-C con­trolled by statin ther­a­py, as stud­ied in RE­DUCE-IT.” 

None of this is go­ing to make it easy for the com­pa­ny, though, with a host of an­gry short in­vestors like­ly to try what­ev­er it takes to fo­ment a back­lash against the da­ta for the last big cat­a­lyst of Q3. Fur­ther com­pli­cat­ing their suc­cess, As­traZeneca has its own out­comes study for the ri­val Epano­va ready to read out next year, while GSK’s Lo­vaza went gener­ic sev­er­al years ago.

But as the morn­ing wore on, it be­came ap­par­ent that Amarin was hold­ing on to its big gains and sup­port­ers are swoon­ing.

Pa­tients en­rolled in RE­DUCE-IT had reg­is­tered an LDL-C lev­el be­tween 41-100 mg/dL (me­di­an base­line LDL-C 75 mg/dL) con­trolled by statin ther­a­py with a slate of car­dio­vas­cu­lar risk fac­tors in­clud­ing: per­sis­tent el­e­vat­ed triglyc­erides be­tween 150-499 mg/dL (me­di­an base­line 216 mg/dL) and ei­ther es­tab­lished car­dio­vas­cu­lar dis­ease or di­a­betes mel­li­tus and at least one oth­er CV risk fac­tor. 

That’s a big mar­ket.

This Phase III has been end­less­ly de­bat­ed as the time drew near for the read­out. Amarin’s Vas­cepa — ap­proved more than 4 years ago for hy­per­triglyc­eridemia — demon­strat­ed its abil­i­ty to sig­nif­i­cant­ly re­duce triglyc­erides in those pa­tients while in­flu­enc­ing bio­mark­ers on in­flam­ma­tion. But as we know from past big car­dio stud­ies, that cer­tain­ly doesn’t nec­es­sar­i­ly trans­late in­to the kind of hard and demon­stra­ble health ben­e­fits such that pay­ers are will­ing to cov­er much larg­er mass pop­u­la­tions of at-risk mem­bers.

RE­DUCE-IT set out to an­swer that ques­tion, with re­searchers en­rolling more than 8,000 pa­tients so they could com­pare it as an add-on to statins in re­duc­ing in­stances of ma­jor ad­verse car­dio­vas­cu­lar events (MACE) as com­pared to statin-treat­ed pa­tients plus place­bo.

We al­ready know from the re­cent AS­CEND study that pop­u­lar fish oil prod­ucts sold in every phar­ma­cy have no clear health ben­e­fits, and Amarin has been built on the no­tion that its high­ly-pu­ri­fied, omega-3 fat­ty acid prod­uct could dis­tin­guish it­self from the sup­ple­ment field. Com­pa­ny ex­ecs said that fish oil’s weak­ness would sim­ply make it eas­i­er to prove Vas­cepa’s val­ue, once the out­comes da­ta were in.

Is it good enough?

Even pos­i­tive car­dio da­ta don’t al­ways trans­late in­to com­mer­cial op­por­tu­ni­ty, and an­a­lysts now will see whether Amarin has come up with da­ta that are good enough to qual­i­fy as the prac­tice-chang­ing event that the com­pa­ny’s back­ers have in­sist­ed would now be in reach.

The dif­fer­ence amounts to a mar­ket with mil­lions of po­ten­tial pa­tients.

Sup­port­ive Jef­feries an­a­lysts who helped build sup­port for the drug’s suc­cess re­cent­ly not­ed:

Pos­i­tive RE­DUCE-IT will be prac­tice chang­ing as it will pro­vide POC that us­ing a high­ly pu­ri­fied Omega-3 drug (vas­cepa) in MD pa­tients on sta­ble statins and rel­a­tive­ly well-con­trolled LDL-C (<100mg/dL) con­tributes to a CV ben­e­fit. While LDL-C has de­creased over decades, TGs con­tin­ue to rise. The mar­ket needs this type of drug.

But for every ad­vo­cate, you could count two more who bet against the drug and any up­beat rise in the share price. The die hards won’t re­treat with­out putting up a fight, but their num­bers were def­i­nite­ly dwin­dling Mon­day.

Im­age: John Thero. AMARIN

Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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A new chap­ter in the de­cen­tral­ized clin­i­cal tri­al ap­proach

Despite the promised decentralized trial revolution, we haven’t yet moved the needle in a significant way, although we are seeing far bolder commitments to this as we continue to experience the pandemic restrictions for some time to come. The vision of grandeur is one thing, but operationalizing and execution are another and recognising that change, particularly mid-flight on studies, is worthy of thorough evaluation and consideration in order to achieve success. Here we will discuss one of the critical building blocks of a Decentralized and Remote Trial strategy: TeleConsent; more than paper under glass, it is a paradigm change and key digital enabler.

John Maraganore, Alnylam CEO (Scott Eisen/Bloomberg via Getty Images)

With lumasir­an on the FDA's doorstep, Al­ny­lam reads out new PhI­II da­ta in PH1

Just over a month away from its December PDUFA date, Alnylam flaunted new data from two Phase III studies to back lumasiran in primary hyperoxaluria type 1 (PH1), a rare liver condition.

The Cambridge, MA-based biotech snagged a priority review for the candidate back in June, and got positive feedback from the EMA’s Committee for Medicinal Products for Human Use just last week. Lumasiran uses RNA interference (RNAi) to silence the gene for glycolate oxidase, an enzyme used in the production of oxalate.

Stephen Hoge, Moderna president (Moderna)

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Weeks away from a potential EUA application, Moderna announced they have completed enrollment in their 30,000-person Phase III Covid-19 vaccine trial, with over a third of volunteers non-white and a quarter over the age of 65.

The announcement caps what has been the most closely-watched recruitment race in the history of drug development, as Pfizer and Moderna rushed to get enough volunteers to prove whether or not experimental vaccines could actually protect people from contracting Covid-19. Pfizer reached that mark on Sept. 15. Moderna said around the same time that they would slow down enrollment to ensure they enrolled enough participants from minority and at-risk groups.

Pfiz­er scoops up an an­tibi­ot­ic in rare M&A deal, bag­ging a vir­tu­al start­up op­er­at­ing on a shoe­string bud­get

Pfizer is stepping up with a rare antibiotics buyout deal today, grabbing Palo Alto, CA-based Arixa Pharmaceuticals in a bid to add a new oral version of avibactam, a beta lactamase inhibitor — or BLI — approved back in 2015 as part of the IV treatment Avycaz.

The Arixa acquisition follows some encouraging Phase I responses demonstrating that 60% to 80% of the oral drug is absorbed into the bloodstream. Only 7% of the IV version is absorbed orally, far below the 30% threshold Arixa has pointed to as a therapeutic threshold. The buyout gives Pfizer’s hospital group a line on a new oral combo with antibiotics like ceftibuten to go after drug-resistant cases of urinary tract infections and other ailments.

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News brief­ing: UK biotech 4D phar­ma heads for Nas­daq via SPAC; Dr. Red­dy's shuts down man­u­fac­tur­ing af­ter cy­ber­at­tack

Another pharma company is intending to use a SPAC to join the Nasdaq.

4D pharma, a UK-based biotech, is reverse-merging with a blank check company in a deal worth up to $37.6 million. The move will give 4D pharma a new Nasdaq ticker, which will be $LBPS, using the American Depositary Share program.

As a result of the move, 4D pharma will gain $14.6 million in cash held by the blank check company, dubbed Longevity. The merger is expected to be completed in early 2021, after which shares will be immediately tradeable.

Can B cells break the bound­aries of cell ther­a­py? Long­wood start­up has $52M to prove a new en­gi­neer­ing tech

Back in December 2017, as the cell therapy world was still basking in the virtually back-to-back approvals of two pioneering CAR-Ts, researchers at Seattle Children’s Research Institute reported a scientific first in a different corner of the field: engineer B cells to treat disease.

The team, led by David Rawlings and Richard James, eventually worked with Longwood Fund to start a biotech around those findings. And now Atlas Venture and RA Capital Management are coming on board to lead a $52 million launch round, joined by Alta Partners, for Be Biopharma.

Jason Kelly, Gingko Bioworks CEO (Mike Blake/Reuters via Adobe)

Ex­clu­sive: Eye­ing big Covid-19 test­ing ex­pan­sion, Gink­go rolls out 50M rapid anti­gen di­ag­nos­tics

In what they hope will be a key part of an extensive effort to boost Covid-19 testing in the US, Ginkgo Bioworks is acquiring and distributing 50 million rapid antigen tests that can potentially be used for virus surveillance in schools and communities and for quick, on the ground diagnoses.

The tests, developed by SD Biosensor, are in line with proposals from the Rockefeller Foundation and Harvard epidemiologists, among others, to blanket the country with fast, low-cost tests. Although not yet authorized in the US, they are a key part of testing efforts from the Bill and Melinda Gates Foundation, who announced plans last month to distribute 120 million of them in low and middle income countries. Roche has commercialized the diagnostic in Europe.

Bo Cumbo, AavantiBio CEO (file photo)

Bo Cum­bo jumps from the top com­mer­cial post at Sarep­ta to the helm of a gene ther­a­py start­up with some in­flu­en­tial back­ers, big plans and $107M

After a 7-year stretch building the commercial team at Sarepta, longtime drug salesman Bo Cumbo is jumping to the entrepreneurial side of the business, taking the helm of a startup that’s got several deep-pocket investors. And he’s not just bringing his experience in selling drugs.

He tells me that when he told Sarepta CEO Doug Ingram about it, his boss got excited about the venture and opted to jump in with a $15 million investment from Sarepta to add to the launch money, alongside 3 of the busiest investors in biotech.

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