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`EP Vantage Vantage Point – As Eliquis limps on Xarelto dominates oral blood thinners
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`9 February, 2016
`
`Export
`
`Vantage Point – As Eliquis limps on Xarelto
`dominates oral blood thinners
`
`ADate October 09, 2013
`
`speedy launch for Eliquis was probably always too much to ask, considering
`that it was the third novel, oral anticoagulant to reach the market. However,
`the tiny sales reported by marketing partners BristolMyers Squibb and Pfizer so
`far this year appear to have surprised sellside analysts, many of whom had
`pinned huge expectations on the product.
`
`Consensus for Eliquis sales next year has dropped 60% in the last 12 months,
`EvaluatePharma data show, and currently stands at $491m. Over the same period,
`expectations for Johnson & Johnson and Bayer’s Xarelto have surged – consensus for sales in
`2014 has jumped by 81% and 60% in the companies’ respective territories, to $1bn and
`$1.4bn. The Eliquis launch is still early but the ultimate potential of this product is now less
`certain, as it appears that Xarelto’s broader label and dosing advantage might have been
`underestimated (see tables).
`
`Missed expectations
`
`With three novel, oral anticoagulants reaching the market at roughly the same time – as well
`as Eliquis and Xarelto, Boehringer Ingelheim launched Pradaxa – differentiation was always
`going to be important to grab share in the biggest target market, stroke prevention in patients
`with nonvalvular atrial f brillation (SPAF).
`
`Both Eliquis and Pradaxa showed superiority over warfarin in preventing stroke, but only the
`BristolMyers pill managed to reduce major bleeding over warfarin and improve mortality. In
`both Europe and the US these superiority claims over warfarin have been reflected on the
`Eliquis label and many analysts assumed this would give the product an edge over the
`competitors.
`
`On approval of Eliquis in the US at the end of 2012, Goldman Sachs analysts wrote that this
`differentiation would drive penetration and reimbursement, adding that they viewed consensus
`for global sales of $350m in 2013 as a “low hurdle”. Cowen analysts were even more effusive:
`“We believe there is no compelling reason to prescribe any other anticoagulant for SPAF,” they
`told their clients.
`
`In reality, Eliquis has limped from the blocks. Consensus for 2013 currently stands at $129m,
`but even this much reduced figure looks unlikely to be hit. Secondquarter sales came in at
`$12m; consensus was $43m.
`
`In its first full year on the market after being approved for stroke prevention, Pradaxa sold
`$875m; Xarelto sold $582m, globally.
`
`Taking time
`
`BristolMyers and Pfizer were not expecting an easy ride and executives cautioned as much at
`the time of the approval, warning investors to expect a slow rollout. Despite huge expectations
`and prophesies of seismic shifts in practice, the launches of all of these products have
`happened slower than many anticipated, with reimbursement and entrenched use of warfarin
`throwing up bigger barriers than were foreseen.
`
`It has also taken time for physicians to embrace these drugs, given the big step change in
`practise they represent, says Dr Ralph Sacco, chairman of neurology at the University of
`
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`Page 1 of 3
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`SENJU EXHIBIT 2304
`LUPIN v. SENJU
`IPR2015-01097
`
`
`
`2/9/2016
`Miami.
`
`EP Vantage Vantage Point – As Eliquis limps on Xarelto dominates oral blood thinners
`
`“They offer tremendous benefit over warfarin – they have less bleeding risk, they are easier to
`use, they have less drug and food interactions. But it takes time for this to penetrate down,
`particularly to the community practitioner,” he says.
`
`Despite all this many analysts were still expecting Eliquis to stop Xarelto in its tracks. But
`prescription data suggests that the impact has been negligible and as such the consensus
`view of the market for these oral thinners has shifted dramatically this year, with numbers for
`Xarelto climbing back up and Eliquis falling, producing the picture in the table below.
`
`Changing outlook for the oral anticoagulants
`% change in
`%
`Current
`%
`Product Company Current
`2014
`change
`2014
`change
`2018
`forecast
`over last
`sales
`over last
`sales
`since
`12
`forecast
`12
`forecast
`launch
`months
`($m)
`months
`($m)
`2,667
`54%
`1,353
`60%
`110%
`
`Xarelto Bayer
`
`Eliquis
`
`Bristol
`Myers
`Squibb
`Johnson
`& Johnson
`Lixiana Daiichi
`Sankyo
`
`Xarelto
`
`2,631
`
`37%
`
`491
`
`60%
`
`68%
`
`1,839
`
`50%
`
`1,005
`
`81%
`
`11%
`
`850
`
`65%
`
`94
`
`17%
`
`22%
`
`First
`launch
`in major
`market
`
`Sep
`2008
`(Europe)
`Sep
`2011
`(US)
`Jul 2011
`(US)
`Jul 2011
`(Japan)
`
`The big gap in this picture is Boehringer Ingelheim’s Pradaxa, which reached the main markets
`first. The company being privately owned, consensus sales forecasts are not available;
`Boehringer reported global sales of $1.43bn last year.
`
`US prescription data indicate that Pradaxa lost market share on the arrival of Xarelto in July
`2011 and continues to do so, while Xarelto demand is still climbing strongly. Eliquis was only
`launched in March, and has so far captured only 1.1% of the market, according to data Bayer
`presented at an investor conference this week; Xarelto is on 19.3% to Pradaxa’s 15.4%, the
`company said.
`
`In part, this will be thanks to Xarelto’s broad label, the widest of all three blood thinners with
`seven approved indications – Pradaxa and Eliquis are only approved in stroke prevention in
`the US.
`
`The J&J/Bayer pill is also approved to treat deep vein thrombosis and pulmonary embolisms,
`and to prevent deep vein thrombosis in patients undergoing knee or hip replacement surgery.
`On top of this Xarelto has generated some positive data in acute coronary syndromes, a
`severely ill patient population in which Eliquis failed and Boehringer declined to test Pradaxa in
`phase III.
`
`European regulators allowed marketing in this setting earlier this year and although the US has
`so far declined to grant approval, evidence of utility in a very hardtotreat population can only
`have helped the drug’s reputation (FDA’s no means no for new blood thinners in acute
`coronary syndrome, March 5, 2013).
`
`Eliquis is due to hear on approval in the albeit smaller presurgery setting in the US in May
`next year – it has already sold for this use in Europe – and this could help bump up demand.
`
`Once vs twice
`
`Dosing is likely to be another factor favouring Xarelto. While both Eliquis and Pradaxa pills
`need to be taken twice a day in stroke prevention, Xarelto is once daily. Tim Race, pharma
`analyst at Deutsche Bank, reckons this could be providing an edge.
`
`“These patients are on many other drugs and once daily fits in best. Also, doctors don't trust
`patients to take their pills, so is [Eliquis] really better in the real world if you miss a dose?” he
`says.
`
`Bayer is convinced that dosing is playing a major part in Xarelto's success. “Physician surveys
`have shown that they use Xarelto over other agents because of its breadth of indications at
`launch and once daily dosing,” Dr Kemal Mal k, head of development and chief medical officer,
`said at Bayer’s presentation yesterday.
`
`Dr Sacco, who was involved in one of the pivotal trials testing Eliquis, agrees that Xarelto’s
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`2/9/2016
`schedule can be an advantage.
`
`EP Vantage Vantage Point – As Eliquis limps on Xarelto dominates oral blood thinners
`
`“Once a day often improves compliance.” But whether any of these drugs is truly better is “the
`million dollar question”, he adds, as there have been no headtoheads, and comparing trials
`results is fraught with the usual caveats.
`
`“It’s really hard to choose between them. Ultimately it comes down to what the physician is
`most comfortable using,” he says.
`
`Inertia
`
`This stance will naturally favour an incumbent, and helps explain Eliquis’s struggles to get off
`the ground, despite being perceived as the safest. As such, it is too early write off the drug as
`an alsoran, although if it still does have marketleading potential it seems this will longer than
`expected to fulfil.
`
`And there is another cloud on the horizon for Eliquis, in the shape of a fourth oral contender –
`Lixiana or edoxaban from Daiichi Sankyo. Like Eliquis and Xarelto this is a Factor Xa inhibitor –
`Pradaxa is a thrombin inhibitor – and is also being tested as a onceaday medicine.
`
`Phase III data released earlier this year, in patients with deep vein or lung blood clots, found
`the project noninferior to warfarin at preventing the recurrence of clots and superior to
`warfarin at preventing bleeding. Superiority on both measures would have been a huge win for
`the Japanese company, but results in the allimportant stroke prevention indication will be the
`real measure of edoxaban. Those data are l kely to emerge at the AHA conference in
`November (ESC – Daiichi joins the USEU bloodthinning race with positive Lixiana data,
`September 2, 2013).
`
`Of course, a strong showing in stroke prevention will mark onceaday edoxaban as a strong
`competitor to all of the anticoagulants. Although Daiichi still has to get the drug to market – the
`FDA did not give Xarelto or Eliquis an easy ride – and then battle in an even more crowded
`market place.
`
`And Bayer and J&J will not let their lead go without a fight – the German company set out
`plans yesterday to recruit another 30,000 patients in trials in additional clotting settings and a
`wider atrial f brillation population, to broaden the label further.
`
`It is undoubtedly early days for Eliquis, and BristolMyers and Pfizer have laid out plans for a
`big marketing push to reinvigorate the launch. But its thirdtomarket handicap and twiceaday
`dosing disadvantage, which were brushed off by the companies and bullish analysts before
`launch, will take time to overcome.
`
`To contact the writer of this story email Amy Brown in London at AmyB@epvantage.com
`or follow @AmyEPVantage on Twitter
`
`This content is written, edited and published by EP Vantage and is distributed by Evaluate Ltd. All queries regarding the
`content should be directed to: news@epvantage.com
`
`EP Vantage is a unique, forwardlooking, news analysis service tailored to the needs of pharma and finance professionals. EP
`Vantage focuses on the events that will define the future of companies, products and therapy areas, with detailed financial
`analysis of events in realtime, including regulatory decisions, product approvals, licensing deals, patent decisions, M&A.
`
`Drawing on Evaluate, an industryleading database of actual and forecast product sales and financials, EP Vantage gives
`readers the insight to make valueenhancing decisions.
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