ESC 2017 – Bleeding blunts Xarelto’s Compass victory

Date August 27, 2017

Expanding into new indications is vital for Bayer and Johnson & Johnson’s blood thinner Xarelto to keep up with its rival Eliquis. Detailed results from the Compass trial should help it do just that, with an impressive 24% reduction in cardiovascular events in coronary or peripheral artery disease patients treated with Xarelto and aspirin, over aspirin alone.

However, it was not all good news for the two groups. The full Compass results, presented today at the European College of Cardiology meeting and published simultaneously in the NEJM, uncovered an increase in bleeding events with Xarelto. Furthermore, the Xarelto-only arm did not show a significant benefit versus aspirin monotherapy.

On the latter point, Peter DiBattiste, who leads cardiovascular development at J&J’s Janssen unit, told EP Vantage: “I think this is what we would’ve expected – thrombosis is both a platelet and coagulation cascade problem. We know aspirin reduces cardiovascular events by 19%. If you add 24% on top of it, that really moves the needle.”

He added: “Xarelto alone isn’t bad. We didn’t test for non-inferiority, but Xarelto [alone] was numerically better than aspirin alone.”

Let it bleed

As for the bleeding risk, Jim List, Janssen’s head of cardiovascular and metabolism, conceded: “There was an increase and that needs to be weighed in the risk-benefit [calculation].”

He stressed that there was no significant difference in the most serious bleeding events: intracranial bleeds, fatal haemorrhages or bleeds into critical organ spaces. Rather, the increased bleeding seen with Xarelto was mainly driven by hospitalisations for bleeding.

And this covered a broad spectrum of cases, with some hospitalisations not as serious as others, according to Mr DiBattiste. “If you went to the emergency room for a nosebleed, that counted as a major bleed.”

Even so, this adverse event could make doctors wary of prescribing Xarelto, which is forecast to lose out to its rival Eliquis, from Bristol-Myers Squibb and Pfizer, in the years to come as the latter’s superior bleeding profile comes to the fore (2017 establishes Eliquis as the blood-thinner to beat, 3 May 2017).

However, Bristol and Pfizer are not carrying out a similar study of Eliquis in coronary or peripheral artery disease, with executives telling EP Vantage that the companies plan to focus on the product's core uses for now. This means that Xarelto could regain the upper hand if it does get the go-ahead for this new use.

J&J, which is responsible for marketing Xarelto in the US, 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.

Follow the Compass

Compass tested whether Xarelto reduced the risk of cardiovascular events – a composite of myocardial infarction, stroke or cardiovascular death. It was already known to be a hit: J&J and Bayer announced in February that the trial had been stopped early for efficacy (Xarelto scores again in huge heart trial, February 9, 2017).

The detailed data show that the combination of Xarelto and aspirin had an effect on two of the three components of the primary endpoint, with a 42% reduction in stroke and a 22% reduction in cardiovascular mortality. The 14% benefit in myocardial infarction did not hit significance.

“We never really expected the components to be significant on their own,” said Mr DiBattiste. “That’s why we use a composite endpoint. All three components moved in the right direction. I’m very confident there’s an effect across all three.”

The J&J executives were reluctant to say how much the new indication could add in sales if it made it onto Xarelto’s label. But with around 27 million Americans suffering from coronary or peripheral artery disease, according to J&J, the treatable population would be large.

Bayer and J&J need to open up this market if they want Xarelto to become the dominant anticoagulant once more.

Product  Study  Trial ID 
Xarelto  Compass  NCT01776424 

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

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