The latest sets of data from the new oral blood thinners, Xarelto and apixaban, presented at the European Society of Cardiology this weekend made pretty good reading for their developers. Efficacy looked solid and safety manageable, if not better than current therapies; exactly what was needed.
Financial analysts expect these two agents to be generating almost $5bn by 2016, consensus data from EvaluatePharma shows. Add the similar anticoagulants also in development such as Boehringer Ingelheim’s Pradaxa and Merck & Co’s (MRK) vorapaxar and the potential market is significantly larger. The fight for market share in this high stakes arena could be hard-won.
The Xarelto phase III study, called Einstein-DVT, was carried out in more than 3,400 patients with deep vein thrombosis in the leg.
Researchers found that patients in the Xarelto arm were 33% less likely to develop clots or have a major bleeding event than those given standard therapy, which consists of a two-drug regimen – Sanofi-Aventis’ (SNY) Lovenox followed by warfarin. This was a secondary measure called net clinical benefit, which combined the primary efficacy endpoint – incidence of recurrent DVT or pulmonary embolism – plus major bleeding events.
On these measures alone, Xarelto was non-inferior to standard therapy on efficacy and bleeding events were similar in both arms, at 8.1%. There was only one case of fatal bleeding in the Xarelto arm and five in the Lovenox and warfarin group.
Of course, the big data for Xarelto will be from the Rocket-AF study, examining whether the drug is better than warfarin at preventing strokes in patients with atrial fibrillation. Read across is tricky, as even Bayer admits. The company’s head of cardiovascular drug development told Reuters at the ESC that the massive difference in the age groups between the two trials alone makes translating the data across very difficult. As such, the American Heart Association meeting in November, when the first real peek at this data will be available, is likely to be an even bigger affair for this drug.
For apixaban, being developed by Bristol-Myers Squibb (BMY) and Pfizer (PFE), stroke prevention data in this much bigger AF patient population is already emerging. The phase III Averroes study was conducted in 5,600 AF patients who cannot take warfarin and are instead being dosed with aspirin. An interim analysis presented at the conference revealed that the annual rate of stroke or systemic embolism was 3.9% in the aspirin group and 1.7% in the apixaban arm. The rate of major bleeding was 1.4% and 1.6% respectively, a non-significant difference.
The bottom line is that apixaban reduced the risk of stroke by 55% compared to aspirin, without raising the risk of bleeding. This will have been exactly the result BMS and Pfizer were hoping for, although again data in a bigger population, in patients taking warfarin rather than aspirin, are still crucial. These will not be due until next year, in a trial called Aristotle.
Some analysts have cautioned that because strokes are much harder to control with aspirin rather than warfarin in the atrial fibrillation population, it is not surprising that apixaban did well in this study. However, none of the other companies developing a new anticoagulant has looked at this patient population, meaning if apixaban makes it to the market, this study could give it a nice edge.
What it also means is that observers are likely to become more confident in the outcome of Aristotle, particularly on the all-important bleeding measure. Results are due later in the first half of next year.
With more and more late stage data emerging, the question of differentiation between these agents is surely going to be asked more regularly.
It will take the Aristotle and Rocket-AF results before more meaningful comparisons can be drawn. But with all these agents producing strong results, as they near the market doctors will be asking which is the best therapy for their patients.
One of these agents could yet see a safety signal emerge yet and with so many jostling for position, that would be bad news. For now, however, things are still looking good and picking a winner is a tough call to make.