J&J's Xarel­to, Amar­in's Vas­cepa are cost-ef­fec­tive, not bud­get friend­ly — ICER

ICER, an in­creas­ing­ly in­flu­en­tial cost-ef­fec­tive­ness watch­dog in the Unit­ed States, has con­clud­ed in its re­view of treat­ments for car­dio­vas­cu­lar dis­ease that while the cost of J&J’s Xarel­to and Amarin’s Vas­cepa meet its bench­mark for val­ue pric­ing — the two treat­ments will not like­ly treat as many pa­tients as hoped with­out sur­pass­ing the an­nu­al bud­get thresh­old cal­cu­lat­ed by ICER for each ther­a­py.

J&J’s Xarel­to, known chem­i­cal­ly as ri­varox­a­ban, is a blood thin­ner that was orig­i­nal­ly ap­proved to pre­vent deep vein throm­bo­sis in pa­tients un­der­go­ing ma­jor or­tho­pe­dic surgery and is wide­ly used in the man­age­ment of atri­al fib­ril­la­tion and ve­nous throm­boem­bol­ic dis­ease. Last year, it was cleared for use in com­bi­na­tion with as­pirin as a treat­ment to re­duce the risk of ma­jor car­dio­vas­cu­lar (CV) events in pa­tients with chron­ic coro­nary or pe­riph­er­al ar­te­r­i­al dis­ease — on the ba­sis of the piv­otal COM­PASS tri­al that in­di­cat­ed that the com­bi­na­tion spurred a 24% re­duc­tion of the risk of ma­jor CV events in the pa­tient pop­u­la­tion.

Amarin’s Vas­cepa, known chem­i­cal­ly as icos­apent eth­yl, is an omega-3 fat­ty acid de­rived from fish oil that was orig­i­nal­ly en­dorsed by the US reg­u­la­tor as a treat­ment for el­e­vat­ed triglyc­erides. How­ev­er, it is now un­der FDA re­view for an ex­pand­ed la­bel af­ter a land­mark tri­al — RE­DUCE-IT — showed the pill trig­gered a 25% re­duc­tion in the risk for the first oc­cur­rence of a ma­jor car­dio event, and a 26% re­duc­tion for 3-point MACE, a com­pos­ite of car­dio­vas­cu­lar death, non­fa­tal heart at­tack and non­fa­tal stroke. The reg­u­la­tor is set to make its de­ci­sion by De­cem­ber.

At cur­rent prices, both drugs fall with­in the val­ue-based price bench­mark range set by ICER:

Source: ICER, 2019

Click on the im­age to see the full-sized ver­sion

Xarel­to’s an­nu­al list price of $5,457 falls with­in ICER’s val­ue-based price bench­mark range of $5,200-$7,600 per year — in fact, the drug’s es­ti­mat­ed net price of $2,215 per year is sig­nif­i­cant­ly low­er than the ICER bench­mark. Clin­i­cal ex­perts at ICER’s pub­lic meet­ing sug­gest­ed they would con­sid­er us­ing the drug in ap­prox­i­mate­ly 30% of el­i­gi­ble pa­tients — but at the cur­rent price — on­ly rough­ly 6% of el­i­gi­ble pa­tients could be treat­ed in a giv­en year with­out cross­ing the po­ten­tial ICER thresh­old of $819 mil­lion an­nu­al­ly. Last year, Xarel­to gen­er­at­ed near­ly $2.5 bil­lion in glob­al sales.

In the case of Vas­cepa, the drug’s an­nu­al list price of $3,699 and es­ti­mat­ed net price of $1,625 are both sig­nif­i­cant­ly low­er than ICER’s val­ue-based price bench­mark range of $6,300-$9,200 per year. Ex­perts at ICER’s pub­lic meet­ing sug­gest­ed they would like to pre­scribe the drug, if ap­proved for the new in­di­ca­tion, to the ma­jor­i­ty of el­i­gi­ble pa­tients — but on­ly about 4% of el­i­gi­ble pa­tients could be treat­ed in a giv­en year with­out cross­ing the ICER thresh­old of $819 mil­lion an­nu­al­ly. In 2018, Vas­cepa gen­er­at­ed rough­ly $229 mil­lion in sales.

ICER’s bud­get thresh­old is based on cal­cu­la­tions that sug­gest that the US health care sys­tem, in the short term, may not be equipped to ab­sorb the ther­a­pies’ ex­pect­ed adop­tion if costs ex­ceed $819 mil­lion per drug, per year — with­out sidelin­ing oth­er drugs/ser­vices or con­tribut­ing to a rapid uptick in in­sur­ance costs.

In terms of long-term ef­fec­tive­ness, ICER found that both ther­a­pies pro­vid­ed gains in over­all sur­vival above and be­yond the cur­rent ar­se­nal of car­dio­vas­cu­lar ther­a­pies. How­ev­er, re­view­ers did high­light some sources of un­cer­tain­ty.

Al­though treat­ment with Xarel­to low­ered the risk of CV events, there was a surge in bleed­ing, re­view­ers not­ed. For Vas­cepa, it is un­clear whether the ther­a­py would be ef­fec­tive in pa­tients not treat­ed with statins — and the min­er­al oil place­bo used in the RE­DUCE-IT tri­al may not have been bi­o­log­i­cal­ly in­ert, they said. In ad­di­tion, al­though the RE­DUCE-IT tri­al test­ed a high­er dose of Vas­cepa, pri­or neg­a­tive re­sults test­ing dif­fer­ent for­mu­la­tions of omega-3 fat­ty acid de­rived from fish oil “have led some to wor­ry that these new re­sults could be wrong by chance.”

“(D)es­pite the re­port’s pos­i­tive con­clu­sion that Vas­cepa is cost-ef­fec­tive, we be­lieve that it un­der­states the true val­ue of Vas­cepa,” Amarin’s chief med­ical of­fi­cer Craig Gra­nowitz said in a state­ment on Thurs­day.

“For ex­am­ple, the re­port’s base-case analy­ses re­flect on­ly the costs of heart at­tack, stroke and car­dio­vas­cu­lar death and ex­clude oth­er high costs as­so­ci­at­ed with oth­er car­dio­vas­cu­lar events demon­strat­ed to be low­ered by Vas­cepa in the RE­DUCE-IT car­dio­vas­cu­lar out­comes study (e.g., revas­cu­lar­iza­tion pro­ce­dures and hos­pi­tal­iza­tion for un­sta­ble angi­na) as well as low­er rates of re­cur­ring car­dio­vas­cu­lar events in pa­tients treat­ed with Vas­cepa dur­ing the study.”

J&J said it had ex­pect­ed ICER to find Xarel­to cost-ef­fec­tive in its new in­di­ca­tion.

“How­ev­er, we do not en­dorse the use of cost-per-QALY or cost-per-life-year-gained analy­sis as the sole or pri­ma­ry ba­sis of de­ci­sion mak­ing,” the com­pa­ny said in a state­ment to End­points News.  

Can­cer may have eclipsed car­dio­vas­cu­lar dis­ease in the de­vel­oped world — al­though CDC es­ti­mates sug­gest it still kills 610,000 in the Unit­ed States every year (that’s 1 in every 4 deaths).

Lessons for biotech and phar­ma from a doc­tor who chased his own cure

After being struck by a rare disease as a healthy third year medical student, David Fajgenbaum began an arduous journey chasing his own cure. Amidst the hustle of this year’s JP Morgan conference, the digital trials platform Medable partnered with Endpoints Studio to share Dr. Fajgenbaum’s story with the drug development industry.

What follows is an edited transcript of the conversation between Medable CEO Dr. Michelle Longmire and Dr. Fajgenbaum, and it is full of lessons for biotech executives charged with bringing the next generation of medicines to patients.

Jim Scholefield via PR Newswire

Mer­ck los­es its chief dig­i­tal of­fi­cer, spot­light­ing tal­ent hunt for the hottest ti­tle in Big Phar­ma

Over the last few years we’ve seen the chief digital officer title become one of the hottest commodities in Big Pharma as global organizations hunt the best talent to sharpen the cutting edge of their tech platforms.

But Merck just discovered how hard it may be to keep them focused on pharma.

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Tim Mayleben (file photo)

Es­pe­ri­on's goldilocks cho­les­terol fight­er wins FDA ap­proval — will its 'tra­di­tion­al' pric­ing ap­proach spur adop­tion?

It’s more effective than decades-old statins but not as good as the injectable PCSK9 — the goldilocks treatment for cholesterol-lowering, bempedoic acid, has secured FDA approval.

Its maker, Esperion Therapeutics, is betting that their pricing strategy — a planned list price of between $10 to $11 a day — will help it skirt the pushback the PCSK9 cholesterol fighters, Repatha and Praluent, got from payers for their high sticker prices.

The sky-high expectations for the pair of PCSK9 drugs that were first approved in 2015 quickly simmered — and despite a 60% price cut, coupled with data showing the therapies also significantly cut cardiovascular risk, sales have not really perked up.

Esperion is convinced that by virtue of being a cheaper oral therapy, bempedoic acid will hit that sweet spot in terms of adoption.

“We’re kind of like the old comfortable shoe,” Esperion’s chief commercial officer Mark Glickman remarked in an interview with Endpoints News ahead of the decision date. “It’s an oral product, once-daily and nontitratable — these are things that just resonate so true with patients and physicians and I think we’ve kind of forgotten about that.”

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James Collins, Broad Institute via Youtube

UP­DAT­ED: A space odyssey for new an­tibi­otics: MIT's ma­chine learn­ing ap­proach

Drug development is complex, expensive and comes with lousy odds of success — but in most cases, if you make it across the finish line brandishing a product with an edge (and play your cards right) it can be a lucrative endeavor.

As it stands, the antibiotic market is cursed — it harbors the stink of multiple bankruptcies, a dearth of innovation, and is consequently barely whetting the voracious appetites of big pharma or venture capitalists. Enter artificial intelligence — the biopharma industry’s cure-all for the pesky process of making a therapeutic, including data mining, drug discovery, optimal drug delivery, and addressable patient population.

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Gilead los­es two more patent chal­lenges on HIV pill, set­ting up court­room fight in Delaware

Gilead sustained two more losses in their efforts to rid themselves of an activist-backed patent lawsuit from the US government over a best-selling HIV pill.

Urged on by activists seeking to divert a portion of Gilead’s revenue to clinics and prevention programs, the Department of Health and Human Services made a claim to some of the patents for the best-selling HIV prevention drug, Truvada, also known as PrEP. Gilead responded by arguing in court that HHS’s patents were invalid.

Today, the US Patent and Trademark Office ruled that Gilead was likely to lose the last two of those challenges as well. The USPTO ruled against Gilead on the first two patents earlier this month.

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Kathy High (file photo)

Gene ther­a­py pi­o­neer Kathy High has left Spark af­ter com­plet­ing $4.3B union with Roche

Kathy High dedicated the past seven years of her life shepherding experimental gene therapies she’s developed at Children’s Hospital of Philadelphia toward the market as president and head of R&D at Spark Therapeutics. Now that the biotech startup is fully absorbed into Roche — with an FDA approval, a $4.3 billion buyout and a promising hemophilia program to boast — she’s ready to move on.

Roche confirmed her departure with Endpoints News and noted “she will take some well-deserved time off and then will begin a new chapter in a sabbatical at a university.”

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Tal Zaks (Moderna via YouTube)

For two decades, a new vac­cine tech­nol­o­gy has been slow­ly ap­proach­ing prime time. Now, can it stop a pan­dem­ic?

Two months before the outbreak, Moderna CMO Tal Zaks traveled from Cambridge, MA to Washington DC to meet with Anthony Fauci and the leaders of the National Institutes of Health.

For two years, Moderna had worked closely with NIH researchers to build a new kind of vaccine for MERS, one of the deadliest new viruses to emerge in the 21st century. The program was one test for a new technology designed to be faster, cheaper and more precise than the ways vaccines had been made for over a century. They had gathered evidence the technology could work in principle, and Fauci, the longtime head of the National Institute of Allergy and Infectious Diseases and a longtime advocate for better epidemic preparedness, wanted to see if it, along with a couple of other approaches, could work in a worst-case scenario: A pandemic.

“[We were] trying to find a test case for how to demonstrate if our technology could rapidly prepare,” Zaks told Endpoints News.

Zaks and Fauci, of course, wouldn’t have to wait to develop a new test. By year’s end, an outbreak in China would short circuit the need for one and throw them into 24/7 work on a real-world emergency. They also weren’t the only ones with new technology who saw a chance to help in a crisis.

An ocean away, Lidia Oostvogels was still on vacation and relaxing at her mother’s house in Belgium when her Facebook started changing. It was days after Christmas and on most people’s feeds, the news that China had reported a novel virus to the World Health Organization blurred into the stream of holiday sweaters and fir trees. But on Oostvogels’s feed, full of vaccine researchers and virus experts, speculation boiled: There was a virus in China, something contained to the country, but “exotic,” “weird,” and maybe having to do with animals. Maybe a coronavirus.

Lidia Oostvogels

“I was immediately thinking like, ‘Hey, this is something that if needed, we can play a role,'” Oostvogels told Endpoints.

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Christos Kyratsous (via LinkedIn)

He built a MERS treat­ment in 6 months and then the best Ebo­la drug. Now Chris­tos Kyrat­sous turns his sights on Covid-19

TARRYTOWN, NY — In 2015, as the Ebola epidemic raged through swaths of West Africa, Kristen Pascal’s roommates sat her down on their couch and staged an intervention.

“Are you sure this is what you want to be doing with your life?” she recalls them asking her.

Special report

Pascal, a research associate for Regeneron, had been coming home at 2 am and leaving at 6 am. At one point, she didn’t see her roommate for a week. For months, that was life in Christos Kyratsous’ lab as the pair led a company-wide race to develop the first drug that could effectively treat Ebola before the outbreak ended. For Pascal, that was worth it.

“I’m ok, I don’t have Ebola,” Pascal told them. “I see that death toll rising and I can’t not do something about it.”

Last August, Regeneron learned they had succeeded: In a large trial across West Africa, their drug, REGN-EB3, was vastly more effective than the standard treatments. It was surprise news for the company, coming just 10 months into a trial they thought would take several years and a major victory in the global fight against a deadly virus that killed over 2,000 in 2019 and can carry a mortality rate of up to 90%.

For Kyratsous and Pascal, though, it brought only fleeting reprieve. Just four months after the NIH informed them REGN-EB3 worked, Kyratsous was back in his office reading the New York Times for updates on a new outbreak on another continent, and wondering alongside Pascal and senior management whether it was time to pull the trigger again.

In late January, as the death toll swelled and the first confirmed cases outside China broke double digits, they made a decision. Soon they were back on the phone with the multiple government agencies and their coronavirus partners at the University of Maryland’s Level 3 bio lab. The question was simple: Can Kyratsous and his team use a process honed over two previous outbreaks, and create a treatment before the newest epidemic ends? Or worse, if, as world health experts fear, it doesn’t vanish but becomes a recurrent virus like the flu?

“Christos likes things immediately,” Matt Frieman, Regeneron’s coronavirus collaborator at the University of Maryland, told Endpoints. “That’s what makes us good collaborators: We push each other to develop things faster and faster.”

Kristen Pascal (Regeneron)

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The first time Regeneron tried to respond to a global outbreak, it was something of a systems test, Kyratsous explains from his office at Regeneron’s Tarrytown headquarters. Kyratsous, newly promoted, has crammed it with photos of his family, sketches of viral vectors and a shark he drew for his 3-year-old son. He speaks rapidly – an idiosyncrasy his press person says has only been aggravated this afternoon by the contents of his “Regeneron Infectious Diseases”-minted espresso glass – and he gesticulates with similar fluidity, tumbling through antibodies, MERS, the novel coronavirus, Ebola-infected monkeys.

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Don't let Ab­b­Vie fool FTC with an easy di­vesti­ture, plead crit­ics in lat­est at­tack on $63B Al­ler­gan buy­out

If the FTC must let AbbVie and Allergan go ahead with their merger, at least make them divest their latest blockbuster on the market, a chorus of unions, consumer groups and public interest organizations plead in a new attempt to rein in the megamerger.

There’s a second part to their argument: If the antitrust watchdog does greenlight the divestiture AbbVie wants, then at least ensure the pharma giant cannot corner its future rivals with its exclusionary tactics.

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