Ex­perts ques­tion Amar­in's ear­ly tout­ing of Vas­cepa da­ta ahead of de­tailed re­sults

At the end of Sep­tem­ber, Amarin teased some ear­ly find­ings for Vas­cepa, its pre­ven­tive med­i­cine for peo­ple at risk of heart dis­ease. The claim was as­tound­ing: a 25% rel­a­tive risk re­duc­tion for deaths re­lat­ed to heart at­tacks, strokes and oth­er con­di­tions. Head­lines pro­claimed a po­ten­tial game chang­er in treat­ing car­dio­vas­cu­lar dis­ease. And com­pa­ny shares quick­ly soared, from $3 a share to about $20.

Vas­cepa is Amarin’s on­ly prod­uct. The com­pa­ny wants to turn its pill made of pu­ri­fied fish oil in­to a cash cow, al­low­ing it to staff up both in the Unit­ed States and abroad so it can sell doc­tors and mil­lions of con­sumers on its med­ical ben­e­fits. Al­though the prod­uct has been on the mar­ket for more than five years, its first TV ad cam­paign rolled out this sum­mer in an­tic­i­pa­tion of the study find­ings.

Ex­cept there is one prob­lem. The par­tic­u­lars of the sci­en­tif­ic study on which this claim was based re­main a mys­tery.

Amarin’s pre­lim­i­nary an­nounce­ment came via a news re­lease on Sept. 24. The com­pa­ny plans to re­lease de­tailed find­ings in No­vem­ber at the na­tion­al Amer­i­can Heart As­so­ci­a­tion con­fer­ence. Then ear­ly next year, it plans to seek FDA ap­proval to use the drug as a pre­ven­tive for a range of heart con­di­tions, be­yond its cur­rent role tar­get­ing high triglyc­eride lev­els.

In the in­ter­im, a bat­tle is brew­ing among physi­cians, car­dio­vas­cu­lar ex­perts and phar­ma watch­ers who say Vas­cepa brings to the fore­ground trou­bling trends in the mar­ket­ing and ad­ver­tis­ing of new drugs. Com­pa­nies some­times pro­mote new prod­ucts, but with­hold the de­tailed find­ings un­til much lat­er. The con­se­quences for both con­sumers and the health sys­tem are vast.

Er­ic Strong

“Un­til all the da­ta is avail­able for re­view by the pub­lic and med­ical com­mu­ni­ty, it’s re­al­ly pre­ma­ture to see some of the cheer­lead­ing that’s be­ing done,” said Er­ic Strong, a hos­pi­tal­ist and clin­i­cal as­sis­tant pro­fes­sor at Stan­ford School of Med­i­cine. “It’s hard­er to change peo­ple’s minds once you have these rosy pic­tures.”

John Thero, Amarin’s CEO, ar­gued that the im­mi­nent re­lease of the drug’s com­plete pic­ture should al­le­vi­ate those con­cerns.

John Thero

In un­veil­ing topline find­ings in a news re­lease, he said, the com­pa­ny’s play­book doesn’t di­verge from that of oth­er phar­ma­ceu­ti­cal mak­ers, and pro­vides a nec­es­sary lev­el of dis­clo­sure for share­hold­ers.

But it’s the specifics in the da­ta — for in­stance, which pa­tients ben­e­fit­ed, by how much, their ab­solute risk re­duc­tion and which pre­cise con­di­tions saw im­prove­ment — that il­lus­trate whether a prod­uct is cost-ef­fec­tive, said med­ical and drug ex­perts.

That’s es­pe­cial­ly true in the case of Vas­cepa, whose man­u­fac­tur­er is work­ing hard to con­vince peo­ple the prod­uct is clin­i­cal­ly su­pe­ri­or to or­di­nary fish oil sup­ple­ments. Fish oil, which can re­tail for a few dol­lars a bot­tle, has long been pro­mot­ed as a pre­ven­tive for heart dis­ease. But the sub­stance has nev­er held up in clin­i­cal tri­als as a way to sys­tem­at­i­cal­ly low­er dis­ease risk, said ex­perts.

That’s where Amarin’s prod­uct is su­pe­ri­or, Thero said.

The man­u­fac­tur­er has tried to lim­it com­pe­ti­tion by seek­ing to block oth­er fish oil prod­ucts —ar­gu­ing to the US In­ter­na­tion­al Trade Com­mis­sion that omega-3 sup­ple­ments aren’t equiv­a­lents, and call­ing on the FDA to block a chem­i­cal com­po­nent of fish oil, known as EPA and mar­ket­ed by a num­ber of sup­ple­ment com­pa­nies, from be­ing sold as a di­etary sup­ple­ment. Amarin hasn’t yet pre­vailed.

Pre­ston Ma­son

Pre­ston Ma­son, a bi­ol­o­gist who con­sults for Amarin and has ad­vo­cat­ed on its be­half, ar­gued that or­di­nary fish oil sup­ple­ments car­ry risks be­cause they are not reg­u­lat­ed or ap­proved by the FDA, which does over­see pre­scrip­tion drugs like Vas­cepa.

How Vas­cepa per­forms against reg­u­lar fish oil re­mains un­known. Amarin’s tri­al com­pared the drug against a place­bo, not over-the-counter sup­ple­ments.

Vas­cepa it­self isn’t new. It was ap­proved in 2012 as a rem­e­dy for ex­treme­ly high triglyc­eride lev­els, which can put pa­tients at risk for pan­cre­at­ic prob­lems. But re­duc­ing that fat hadn’t been con­clu­sive­ly tied to, say, low­er­ing the risk of heart at­tacks, or oth­er ma­jor car­diac prob­lems.

That link, os­ten­si­bly, is what Amarin is try­ing now to as­sert. And there’s plen­ty of mon­ey to be made if it suc­ceeds.

As of last De­cem­ber, Vas­cepa re­tailed for about $280 for a month-long sup­ply, a list price in­crease of 43% over five years, though the com­pa­ny says its net sale price has stayed the same. (That dif­fer­ence would come if Amarin in­creased the size of re­bates, or dis­counts it pro­vides, com­men­su­rate with price hikes.)

Now, cit­ing the drug’s po­ten­tial­ly in­creased val­ue, Amarin has de­clined to say whether it will change the price again — though Thero said he sees greater prof­it po­ten­tial if the com­pa­ny in­creas­es sales vol­ume rather than price.

This gets at the crux of this de­bate. If a com­pa­ny makes avail­able the tech­ni­cal de­tails of a prod­uct, but on­ly af­ter hyp­ing the find­ings, and if the de­tails un­der­cut some of that buzz — is it too late?

Cour­tesy KHN

Click on the im­age to see the full-sized ver­sion

Khur­ram Nasir, a Yale car­di­ol­o­gist, ac­knowl­edged that it’s un­clear how ef­fec­tive Vas­cepa re­al­ly is, but main­tained those am­bi­gu­i­ties will be cleared up soon enough.

Khur­ram Nasir

“As the find­ings re­veal them­selves, there will be a lot of dis­cus­sion around cost ef­fec­tive­ness, and whether this is worth the spend,” Nasir said.

Ma­son, the Amarin sci­en­tist, said FDA scruti­ny can al­so al­le­vi­ate con­cerns about over­hype.

But oth­ers wor­ry the per­cep­tion of Vas­cepa’s ef­fec­tive­ness is now set.

Lisa Schwartz

“Peo­ple are weigh­ing in with re­al­ly strong lan­guage, with­out enough in­for­ma­tion,” said Lisa Schwartz, who co-di­rects the Dart­mouth In­sti­tute’s Cen­ter for Med­i­cine and Me­dia and stud­ies ef­fec­tive sci­en­tif­ic com­mu­ni­ca­tion.

That has both clin­i­cal and fi­nan­cial con­se­quences, she added. Doc­tors are more like­ly to pre­scribe a prod­uct that’s been heav­i­ly pro­mot­ed, even if sub­se­quent dis­cus­sion in­di­cates the drug isn’t as pow­er­ful as ini­tial­ly im­plied. And man­u­fac­tur­ers can cash in, whether through in­creased com­pa­ny stock mar­ket val­ue or by charg­ing high­er list prices.

For Vas­cepa, the cen­tral ques­tion is which spe­cif­ic heart con­di­tions saw risk re­duc­tion, she and oth­ers said. In its news re­lease, Amarin not­ed a “com­pos­ite out­come” — that is, the 25% rel­a­tive im­prove­ment en­com­passed all con­di­tions for which the re­searchers test­ed.

Steven Woloshin

“Peo­ple are say­ing, Wow, it re­duced heart at­tack, stroke and blah, blah, blah — when it may just re­duce the least im­por­tant one,” said Steven Woloshin, Schwartz’s re­search part­ner.

An­oth­er is­sue: The Vas­cepa tri­al fo­cused on a spe­cif­ic pop­u­la­tion — pa­tients with high triglyc­eride lev­els plus el­e­vat­ed risk of car­dio­vas­cu­lar dis­ease or di­a­betes who were al­ready tak­ing a dai­ly statin. That means any proof of ben­e­fit is lim­it­ed to that group.

Woloshin and Schwartz both sug­gest­ed that nu­ance could get lost in trans­la­tion. “It is this much nar­row­er, high-risk pop­u­la­tion,” Schwartz said.

Woloshin added, “The fear is [the mes­sage] would gen­er­al­ize to any­one with high triglyc­erides.”

This con­cern is am­pli­fied by a 2016 court set­tle­ment in which the FDA per­mit­ted Amarin to mar­ket Vas­cepa to au­di­ences for whom it hasn’t been specif­i­cal­ly ap­proved — so long as the com­pa­ny doesn’t say any­thing un­true about the drug.

Thero said Amarin’s mar­ket­ing of Vas­cepa has stayed, and will re­main, con­sis­tent with what is fac­tu­al and rel­e­vant.

“We are pro­ceed­ing con­sis­tent­ly with what the FDA has guid­ed,” he said.

But, some ex­perts said, the 2016 set­tle­ment could un­lock the door to wider mar­ket­ing of Vas­cepa’s off-la­bel use, im­ply­ing the pill ben­e­fits more peo­ple than it ac­tu­al­ly does.

Ameet Sarpat­wari

“They’ll take pains to show how dif­fer­ent this is from every­thing out there … and its re­sults in these pop­u­la­tions,” said Ameet Sarpat­wari, an epi­demi­ol­o­gist and lawyer at Har­vard Med­ical School, who stud­ies the phar­ma­ceu­ti­cal in­dus­try. “What they can’t do is say it will be ben­e­fi­cial to these oth­er pop­u­la­tions. But they can hint at that.”

By She­fali Luthra. Orig­i­nal­ly post­ed at Kaiser Health News, a na­tion­al health pol­i­cy news ser­vice that is part of the non­par­ti­san Hen­ry J Kaiser Fam­i­ly Foun­da­tion.

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Chas­ing Roche's ag­ing block­buster fran­chise, Am­gen/Al­ler­gan roll out Avastin, Her­ceptin knock­offs at dis­count

Let the long battle for biosimilars in the cancer space begin.

Amgen has launched its Avastin and Herceptin copycats — licensed from the predecessors of Allergan — almost two years after the FDA had stamped its approval on Mvasi (bevacizumab-awwb) and three months after the Kanjinti OK (trastuzumab-anns). While the biotech had been fielding biosimilars in Europe, this marks their first foray in the US — and the first oncology biosimilars in the country.

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Vas Narasimhan, AP Images

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The numbers are running a bit better than expected, the pipeline — which he assembled as development chief — is performing and the stock popped more than 4% on Thursday as the executive team ran through their assessment of Q2 performance.

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Actually, not much. But Tim Anderson at Wolfe pressed Narasimhan and his development chief John Tsai to pick which of two looming Phase III readouts with blockbuster implication had the better odds of success.

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Dokomajilar notes:

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Part club, part guide, part land­lord: Arie Bellde­grun is blue­print­ing a string of be­spoke biotech com­plex­es in glob­al boom­towns — start­ing with Boston

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