Spotlight – Xarelto and Eliquis's blood feud

In the battle of the anticoagulants, Eliquis’s superior label looks like it is finally about to win out. Bristol-Myers Squibb and Pfizer’s drug, approved at the end of 2012, is forecast to overtake Bayer and Johnson & Johnson’s Xarelto by 2020, according to EvaluatePharma.

But Bayer and J&J, losing ground in Xarelto’s current indications, are fighting back by trying to expand Xarelto into new uses. With five sizeable trials reading out between now and 2019, the question is whether the huge investment will be worth it for a drug due to come off patent in 2024 (see tables below).

The gamble seems to have paid off in coronary and peripheral artery disease, where Xarelto recently posted impressive results in the 27,000-patient Compass trial (ESC 2017 – Bleeding blunts Xarelto’s Compass victory, August 27, 2017). 

Around 16.5 million patients have stable CAD and another 10 million have PAD in the US, according to J&J – a much larger population than the five million US patients with atrial fibrillation, where Xarelto and Eliquis are already approved to prevent stroke.

Approval in CAD/PAD could boost Xarelto sales by $1.2bn by 2022, Wells Fargo analysts believe, based on 20% and 25% penetration of the respective markets.

Pushing into new uses was a gamble that J&J and Bayer probably had to take, with Eliquis boasting a superiority claim over warfarin on both stroke prevention and bleeding; Xarelto has only shown non-inferiority.

Focused

This explains Bristol and Pfizer’s contrasting strategy: concentrating on Eliquis’s core indications. “We’ve made a strategic decision to focus on the area where we think Eliquis can provide the maximum benefit: preventing stroke and systemic embolism in patients with atrial fibrillation,” Christoph Koenen, who leads Eliquis's development for Bristol-Myers, told EP Vantage at last month’s European Society of Cardiology meeting in Barcelona.

“We know that a lot of patients with AF are not well treated, most likely because physicians are really worried about the risk of bleeding,” added Christina Masseria, senior director of outcomes and evidence for Pfizer. “We think there’s a huge unmet need in AF – there’s so much still to do there that we don’t want to get distracted.”

Maybe it is also a question of priorities, with the likes of Bristol having immuno-oncology assets vying for its attention. 

EvaluatePharma sellside consensus now has Eliquis catching Xarelto by 2020 – a previous analysis had the latter still ahead in 2022 (2017 establishes Eliquis as the blood-thinner to beat, May 3, 2017). It will be interesting to see whether this swings back in Xarelto’s favour in light of the Compass results.

Xarelto vs Eliquis
Sales forecasts ($bn)
Product Companies 2017 2018 2019 2020 2021 2022 12-mnth change in 2022 forecast*
Xarelto Bayer/Johnson & Johnson 5.6 6.2 6.8 7.4 8.0 8.5 +11%
Eliquis Bristol-Myers Squibb/Pfizer 4.8 5.8 6.7 7.5 8.1 8.8 +62%
*Current 2022 vs consensus in August 2016; Source: EvaluatePharma.

J&J plans to submit the Compass data to the US FDA by the end of the year, with a goal of getting the PAD/CAD indication onto the label by the second half of 2018. J&J markets Xarelto in the US, while Bayer is responsible for the product in the rest of the world.

There could be further label expansion to come. J&J has already filed Xarelto for long-term use to prevent recurrent venous thromboembolism after a win in the Einstein Choice trial, with an FDA decision due by October 28.

And at ESC, J&J executives highlighted five more trials that could move Xarelto into new indications. None is as big as Compass, but with 31,200 patients enrolled across the studies the outlay is significant.

Xarelto's label expansion trials
Trial Indication N ID Results
Einstein Choice Long-term prevention of recurrent symptomatic VTE 3,396 NCT02064439 Both doses met primary endpoint
Compass Prevention of major cardiovascular events in coronary or peripheral artery disease 27,395 NCT01776424 Xarelto plus aspirin, met primary endpoint
Navigate Esus Prevention of secondary stroke in patients with stroke of undetermined source 7,000 NCT02313909 Primary completion Jan 2018
Mariner Prevention of VTE in post-hospital discharge high-risk patients 12,000 NCT02111564 Primary completion May 2018
Commander HF Prevention of major cardiovascular events in heart failure patients 5,000 NCT01877915 Primary completion May 2018
Cassini Prevention of VTE in cancer patients 700 NCT02555878 Primary completion Jul 2018
Voyager PAD Prevention of major thrombotic vascular events in patients undergoing lower extremity revascularisation procedures 6,500 NCT02504216 Primary completion Jan 2019
Total 61,991
Source: Clinicaltrials.gov.

“Our strategy, from day one, has been to explore areas where no one else has gone,” Peter DiBattiste, who leads cardiovascular development at J&J’s Janssen unit, told EP Vantage at ESC.

Sometimes this strategy has not worked – Xarelto got knocked back by the FDA twice in acute coronary syndrome, although it is approved for this use in Europe.

But this does not seem to faze Mr DiBattiste. “I think we can say that this is the single largest development programme that has ever been done for any compound. In phase III we studied well over 120,000 patients, and with real-world trials it’s about 275,000 patients.”

Xarelto has certainly been a big money spinner for J&J, but the massive ongoing investment has surely hit profitability at a time when other groups might be taking their foot off the gas. The company needs these trials to succeed, and a spike in sales to follow, to justify taking this risk.

To contact the writer of this story email Madeleine Armstrong in London at madeleinea@epvantage.com or follow @ByMadeleineA on Twitter

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