Bayer and Johnson & Johnson’s Janssen Research & Development have acknowledged that their Xarelto® (rivaroxaban) has failed a Phase III trial assessing the blockbuster anticoagulant in patients with a recent embolic stroke of undetermined source (ESUS).
The companies said the Phase III NAVIGATE ESUS missed its primary efficacy endpoint of superiority over aspirin in reducing the risk of stroke (ischemic, hemorrhagic, and undefined stroke; transient ischemic attack with positive neuroimaging) and systemic embolism.
NAVIGATE ESUS was halted early at the recommendation of the study’s Independent Data Monitoring Committee, after a planned interim analysis showed comparable efficacy between patients treated with Xarelto and those treated with aspirin for secondary prevention of stroke and systemic embolism.
The analysis also concluded that Xarelto stood “little chance” of showing overall benefit if the study were completed, Bayer and Janssen added in separate statements.
“Patients with ESUS currently have limited treatment options, and the role of anticoagulants in this area remains uncertain. We will now analyze the data from NAVIGATE ESUS to better understand this outcome and its implications,” Joerg Moeller, M.D., member of the executive committee of Bayer's Pharmaceutical Division and head of development, said in a statement.
He added that patients will be contacted by their physician to switch to aspirin—and that clinical development of Xarelto would continue: “We are committed to continuing the extensive investigation of rivaroxaban for patients at risk of deadly blood clots.”
The Phase III NAVIGATE ESUS study enrolled 7214 patients from 459 sites across 31 countries. Patients were randomized to either rivaroxaban 15 mg once daily or aspirin 100 mg once daily alone.
The study’s primary safety endpoint was major bleeding according to the criteria of the International Society on Thrombosis and Haemostasis. Bleeding rates were “very low overall and within the expected range,” Janssen said, though both companies acknowledged that increased bleeding was observed in the rivaroxaban arm compared to the low-dose aspirin arm.
Bayer and Janssen said a complete data analysis is expected to be presented in 2018, at an unspecified upcoming medical meeting.
Maintaining Sales Forecast
Despite Xarelto’s failure in NAVIGATE ESUS, Bayer continued to project that sales of the drug will exceed €5 billion ($5.85 billion) this year, Reuters reported.
Xarelto sales are already more than halfway there, according to quarterly results released by the companies. During the first half of 2017, Xarelto racked up a combined $3 billion—consisting of €1.585 billion ($1.852 billion) reported by Bayer, and $1.155 billion reported by J&J.
However, during the second quarter, Bayer and J&J both reported less growth year-over-year for Xarelto than Bristol-Myers Squibb did for its rival blockbuster blood thinner Eliquis® (apixaban). While Eliquis’ $2.277 billion in January–June 2017 sales still trailed Xarelto, BMS enjoyed a 51% increase over a year ago, compared with a 20.1% increase for Bayer and a 0.5% decrease for J&J.
The sales gap between the two drugs narrowed during Q2, for which Bayer reported €703 million ($822.5 million) in Q2 Xarelto sales, and J&J, $642 million—a combined $1.464.5 billion, compared with BMS’ $1.176 billion for Eliquis.
Additional competitive pressure comes from another anticoagulant, Boehringer Ingelheim’s Pradaxa® (dabigatran etexilat), which finished last year with sales of €1.385 billion ($1.62 billion) and is also expected to gain sales this year.
During the Q2 conference call with analysts on July 18, J&J Chairman and CEO Alex Gorsky cited a two-point increase in Xarelto’s total prescription market share among cardiovascular metabolic therapeutics due to a decline in warfarin use.
“We feel optimistic about the future of Xarelto, and while there will undoubtedly be pricing pressure, we think that by continuing to differentiate the brand with strong clinical information, strong value information, as well as frankly there is execution in the field, that we'll be well positioned going forward,” Gorsky said according to a transcript published by Seeking Alpha.
ESUS was among new indications being pursued for Xarelto by Bayer and J&J. On June 28, Janssen said it won FDA Priority Review for its supplemental New Drug Appication (NDA) to update the prescribing information for Xarelto by adding a lower 10-mg dose of the drug to reduce patients' risk of recurrent venous thromboembolism (VTE) after at least six months of standard anticoagulation therapy.
The accelerated review advances the FDA’s Prescription Drug User Fee Act (PDUFA) target date to October 28, 2017.