Bayer investors breathed a collective sigh of relief today with the release of highly-anticipated Rocket-AF data on Xarelto at the American Heart Association (AHA) meeting. Shares in the German group surged as much as 7% to €58.06, a two-and-a-half-year high, as fears the drug might fail to beat warfarin in preventing stroke faded and focus switched to its perceived safety benefit (Xarelto data from Rocket trial questions lift-off potential, November 1, 2010).
Xarelto is clearly an approvable drug in the biggest market for new oral anticoagulants; the debate about how it will compete with Boehringer Ingelheim’s Pradaxa now begins in earnest. This rivalry could explain why Bayer's stock quickly slipped back to €55.23 after the initial surge, with much discussion by the expert panel at AHA focusing on the nuances of the risk/benefit profile of the drug against the inescapable conclusion that Xarelto is only comparable to warfarin on overall safety and efficacy (Boehringer's landmark Pradaxa approval sets high benchmark for rivals, October 20, 2010).
In terms of headline data, Xarelto cut the risk of stroke and embolism compared to warfarin by 21%, in patients who completed the trial, the per protocol population. If all patients are included, the intent to treat population, the benefit of the two agents is comparable. For reference, Pradaxa demonstrated a 35% reduction in the risk of stroke and embolism over warfarin. On bleeding, Xarelto showed no increase over warfarin.
Ahead of a big presentation to the conference later, the full data was first presented to the press by a panel of physicians. Much of the debate, which is likely to be echoed later, centred on the differences between the per protocol (PP) and intent to treat (ITT) assessment of Xarelto’s performance against warfarin.
Dr Robert Califf, vice chancellor for clinical research at Duke University School of Medicine and member of the Rocket-AF steering committee, presented the data. He claimed the PP assessment which showed a superior reduction in strokes while patients were taking the drug was a valid conclusion.
Discussing the results, Dr Elaine Hylek of Boston University Medical School, was concerned by the miss on ITT and questioned the validity of PP analysis in a “real world setting”.
The fact remains that on ITT Xarelto was not superior and this measure ultimately remains the gold standard in demonstrating clear superiority.
This debate is likely to rage for some time and while comparisons with Pradaxa will be made, Dr Califf believes “there is no scientifically valid way to compare the two so we’re going to be left with our feelings”.
With regard to the trial itself, there was consensus that the design and baseline patient population, which contained patients with much higher cardiovascular risk than the RE-LY trial supporting the recent approval of Pradaxa, was particularly ambitious. Conclusions about Xarelto’s effectiveness should bear this in mind, the doctors said.
So far the Rocket-AF data has only been presented to journalists; the real test will be how doctors react to the results and how they view the relative merits of Xarelto and Pradaxa.
Further reaction and analysis from AHA to follow.
|Trial ID||NCT00403767 (Rocket-AF)|