EU backing for Eliquis in stroke prevention bodes well for US decision

Bristol-Myers Squibb and Pfizer are getting over the disappointment of 2012’s setbacks for Eliquis. European approval of the blood thinner in the key stroke prevention indication unlocks a revenue stream projected to exceed $1bn by the end of the decade.

Getting approval in the European Union makes Eliquis the third novel agent to replace warfarin for those atrial fibrillation patients at risk of stroke, after Boehringer Ingelheim’s Pradaxa and Bayer and Johnson & Johnson’s Xarelto. It should also build confidence that Eliquis will get the FDA’s nod following an initial rejection based on data issues from the pivotal Aristotle trial (Eliquis FDA setback turns up the heat on Pfizer and Bristol-Myers Squibb, June 25, 2012).

Positive signs

The US and European regulators on occasion march to the beat of different drummers, as demonstrated by the FDA’s first-pass rejection.

Safety probably is not an issue in the US – in addition to nearly 60,000 patients that have been enrolled in phase III trials, Eliquis has been on the European market since May to prevent thromboembolic events, so a real-life safety database has been building in addition to the trial population.

Rather, it is probable that the data issues raised by the FDA will surround the efficacy claims that Bristol-Myers and Pfizer will be able to make on the label after approval. A US decision is expected by March 17.

Bristol-Myers needs Eliquis to succeed – the drug is expected to be the New York company’s biggest seller and biggest growth driver in 2018, with a forecast $3.7bn in revenue, according to EvaluatePharma’s consensus. It is hardly less important to Pfizer: the forecast $1.9bn in alliance revenue puts it on a par with the sales from the wholly owned rheumatoid arthritis drug Xeljanz, approved earlier this month.

The complete response letter in June knocked 3% off Bristol-Myers’ market capitalisation. The cut would have been far deeper had the regulator asked for new trials, but with the expectation that the data issues can be resolved investors have retained faith in management’s ability to get Eliquis to market in the US.

From a revenue perspective the win in Europe should not be overlooked: analysts from UBS forecast $1.3bn in sales from the continent in 2020, compared with $1.5bn in the US.

Dimming outlook

The US knockback, however, has caused a noteworthy change in the outlook. The 2018 forecast has fallen by more than a fifth since then, although the forecasts of fellow factor Xa inhibitor Xarelto, and Pradaxa, the third new blood-thinner fighting in this indication, have not fared much better.

In part, this is because exuberance about the new agents has waned. Warfarin has proven more resilient to competition than originally expected – pricing and safety questions for Pradaxa and efficacy issues for Xarelto have been blamed (Warfarin proves resilient against oral blood thinners, August 21, 2012). Analysts from Morgan Stanley have also raised questions over the size of the warfarin-intolerant population.

Eliquis is widely believed to be the most effective of the three bloodthinners – the pivotal Aristotle trial proved its superiority to warfarin in both preventing stroke and in reducing the rate of major bleeding incidents, a standard neither Pradaxa nor Xarelto met. But the fear is that in its late entry the Bristol-Myers candidate will have missed out on a bolus of warfarin-intolerant patients and will only be attracting the newly diagnosed.

A delayed US launch has definitely affected Eliquis's sales trajectory, setting back the year it is forecast to become the biggest selling of the three from 2014 to 2015.

The good news for Bristol-Myers and Pfizer is that the bad news appears to be out of the way for Eliquis. US approval still seems likely, and the EU’s endorsement should only strengthen that view.

To contact the writer of this story email Jonathan Gardner in London at [email protected]

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