It might be a surprise to learn that Eliquis was Bristol-Myers Squibb’s best-selling drug last quarter, ahead of Opdivo. But the company and its partner Pfizer believe that the blood thinner can become even bigger, helped by a push into new uses.
Like Johnson & Johnson and Bayer with their rival anticoagulant, Xarelto, Bristol and Pfizer are attempting to expand Eliquis into possible new indications – but the two sets of companies are taking slightly different approaches. While Xarelto has been trialled in many different realms, Eliquis's programme has mainly stuck to the atrial fibrillation space.
Still, among the next readouts for both products will be in a new population: the prevention of venous thromboembolism (VTE) in patients with cancer, setting up a rare chance to see how the agents stack up in similar trials.
At the recent European Society of Cardiology meeting, Christoph Koenen, Bristol’s head of cardiovascular development, highlighted Caravaggio, an investigator-led but company-funded study in this setting; meanwhile, Xarelto’s Cassini trial is due to finish this year (ESC 2018 – J&J not downhearted after Xarelto stumbles, August 28, 2018).
|Highlighted Eliquis label-expansion trials|
|Study||Setting||Trial ID||Primary completion|
|Caravaggio*||Prevention of VTE in solid tumours||NCT03045406||Dec 2018|
|Augustus||Atrial fibrillation patients with acute coronary syndrome||NCT02415400||Dec 2018|
|Artesia*||Patients with subclinical atrial fibrillation||NCT01938248||Dec 2020|
|*Investigator-led trial. Source: company communications, clinicaltrials.gov.|
The VTE prevention indication has been a tough nut to crack; the ESC congress saw the failure of the Mariner trial of Xarelto in medically ill patients discharged from hospital. And the Adopt study of Eliquis in a slightly different setting, extended-duration therapy in patients still in hospital, also flunked, in 2011.
“This medically ill patient population is very complicated and heterogeneous, so showing a positive effect has proven to be very difficult,” admitted Mr Koenen.
The developers of both Eliquis and Xarelto obviously hope that homing in on a more specific population, in this case cancer patients, could improve their chances of success.
Mr Koenen also pointed to two more important trials of Eliquis: Augustus, in atrial fibrillation patients who have had a recent coronary event, and Artesia, another investigator-led study in what is known as subclinical atrial fibrillation – asymptomatic arrhythmias that are only detected via implantable devices.
Strengthening the core?
The Bristol exec noted that Augustus and Artesia both aimed to expand Eliquis’s use in one of its core indications, namely the prevention of stroke in patients with atrial fibrillation. This makes it different from J&J and Bayer’s strategy with Xarelto, with many of that drug’s label-expansion studies looking at brand new settings.
For example, the Compass trial of Xarelto, which yielded positive data last year, evaluated the drug’s impact on cardiovascular events in patients with stable coronary or peripheral artery disease – but did not include those with atrial fibrillation. Similarly, the failed Commander HF trial of Xarelto in heart failure also excluded atrial fibrillation patients (ESC 2018 – Xarelto again fails to Command an advantage, August 27, 2018).
In contrast, in heart failure Bristol and Pfizer are evaluating Eliquis specifically in patients who also have atrial fibrillation. “We’re more interested in these patients because the risk there is higher, so the potential benefit would be higher as well,” Mr Koenen told Vantage.
A cynic might say that this approach has another advantage: the atrial fibrillation plus heart failure population is covered by Eliquis’s existing label, meaning the companies are able to use real-world data in this setting, thus avoiding the need to carry out expensive randomised controlled trials.
Danny Wiederkehr, Pfizer’s health economics and outcomes research head, told Vantage that cutting costs was not the main motivation for this strategy. “Trials are always going to be the foundation, but real-world data allow us to drill down into populations that maybe didn’t have a large enough sample in the trial in order to say anything particularly conclusive.”
And Bristol’s Mr Koenen also believes that there is a place for both approaches: “We want to make sure we use the right method to answer the question. Can real-world data help us, or is a randomised clinical trial the best way to go?”
Clinical trials would only be necessary “when we want to look at a very specific population and it would prove difficult to do that in the real world because we couldn’t easily extract all the information we’d need from a claims database”, he added.
While real-world data are gaining greater acceptance, Mr Koenen admitted that there was still a way to go before it might be used more broadly, for example during the approval process. “It’s not happening now – but I think everyone expects it to happen at some point.”
The sellside forecasts Eliquis to become by far the biggest factor Xa inhibitor by 2024, with sales of $11.3bn, according to EvaluatePharma consensus. Xarelto, meanwhile, is expected to peak at $9.6bn in 2022 when its European patents are set to expire.
|Eliquis vs Xarelto|
|Xarelto||Johnson & Johnson/Bayer||6.3||7.9||9.6||5.8|
Factors other than the companies’ respective label-expansion efforts are probably at play here. Eliquis looks like the better drug, having shown superiority to warfarin on both stroke prevention and bleeding; Xarelto has only shown non-inferiority. But Xarelto’s head start has meant that it has so far been able to stay ahead of its rival – although Eliquis is expected to gain the upper hand this year.
Bristol and Pfizer’s label-expansion efforts might be a tacit admission that they need to do more to make the most of their blockbuster blood thinner. But, unlike J&J and Bayer, the companies still believe that sticking as closely as possible to what they already know is the way forward.
This story has been updated to reflect the fact that Augustus and Artesia are studies of Eliquis.