brain imagesThe European Medicines Agency (EMA) has reaffirmed the positive benefit-risk balance of rivaroxaban (Xarelto) for stroke prevention in patients with atrial fibrillation.

The announcement follows an investigation by the Committee for Medicinal Products for Human Use (CHMP) into the malfunctioning of the INR device used in the ROCKET AF trial, in a bid to determine if this had any impact on the study results.

The EMA concluded that a defect with the INR device used in the ROCKET study does not change its conclusions on the overall safety or benefit-risk balance of rivaroxaban. Additionally, Bayer and its development partner Janssen conducted their own thorough analysis and shared their results with health authorities, including EMA and the FDA, while a re-analysis was also conducted by the ROCKET AF Executive Committee, which was recently published online in the New England Journal of Medicine.

Following its investigation the EMA concluded that a defect with the INR device used in the ROCKET study does not change its conclusions on the overall safety or benefit-risk balance of rivaroxaban. 

The EMA said that: “After further analyses of the ROCKET study data taking into account the defect in the INR device, EMA’s Committee for Medicinal Products for Human Use (CHMP) concluded that any incorrect measurements obtained with the defective device would have had only a marginal effect on the study results, and the safety of Xarelto remains unchanged. In addition, data from other large studies confirmed the comparative safety of the medicine and showed similar rates of bleeding in their warfarin groups.” 

Therefore the EMA states: “This means that Xarelto can continue to be used as before, in line with the current prescribing information.”

Professor Keith A. A. Fox, Duke of Edinburgh Emeritus Professor of Cardiology of the University of Edinburgh, Scotland and Member of the ROCKET AF Executive Committee, said: “As a member of the ROCKET AF Executive Committee but equally important as a physician the re-analysis provides me with additional confidence in the strength and robustness of the ROCKET AF trial. It is valuable to be able to provide reassurance to my fellow colleagues but also to our patients and their carers about the evidence for the benefits of rivaroxaban in protecting people with atrial fibrillation from the risk of a stroke.” 

Dr Michael Devoy, Head of Medical Affairs & Pharmacovigilance of Bayer AG’s Pharmaceuticals Division and Bayer Chief Medical Officer, said: “We are very pleased with EMA’s assessment confirming the positive benefit-risk profile of Xarelto for stroke prevention in patients with atrial fibrillation.

“EMA’s assessment follows the conclusions from Bayer and Janssen and those from the independent ROCKET AF Executive Committee that the ROCKET AF data are robust. The re-analyses are reassuring and will provide physicians with additional confidence to prescribe Xarelto for their patients with atrial fibrillation at risk of stroke."

The investigation followed on from an announcement from Alere Inc, which issued a device correction notice for its INR device that is used to monitor INR values in patients using warfarin. Bayer and Janssen were not notified at that time. When the companies became aware of the device correction notice, in September 2015, they reached out to the manufacturer for more information. Upon confirmation from the manufacturer that the devices used in ROCKET AF should have been included in the device correction notice, Bayer and Janssen notified health authorities around the world, including EMA and the FDA and conducted a number of analyses to assess any potential impact on the primary efficacy and safety results of the ROCKET AF clinical trial. These analyses confirm the results of the ROCKET AF study and the positive benefit-risk profile of rivaroxaban in patients with non-valvular atrial fibrillation. During the conduct of the ROCKET AF trial (2006-2010), the INR devices were approved for use by the FDA and available on the market in the US and EU (CE mark).