The Mariner study is a phase three trial in a population similar to the approved indication for Betrixaban. In the Mariner study Xarelto treatment starts post-discharge and continues for 35 days. It is the same formulation that failed the Magellan study in a similar population. Magellan was similar in design to the Apex study. Xarelto was compared to Enoxaparan for the duration of the hospital stay and then to placebo for the post discharge period. From Magellan:
"Net Clinical Benefit or Harm
By day 10, an event of the primary efficacy outcome or major or clinically relevant nonmajor bleeding (the measure of net clinical benefit or harm) had occurred in 216 of 3266 patients (6.6%) in the rivaroxaban group, as compared with 151 of 3291 patients (4.6%) in the enoxaparin group (relative risk, 1.44; 95% CI, 1.18 to 1.77; P<0.001) (Table 3). By day 35, an event of this composite outcome had occurred in 286 of 3042 patients (9.4%) in the group that received extended-duration rivaroxaban, as compared with 240 of 3082 patients (7.8%) in the group that received enoxaparin followed by placebo (relative risk, 1.21; 95% CI, 1.03 to 1.43; P=0.02) (Table 3)."
For the in hospital period, Xarelto equaled Enoxaparan efficacy but failed on safety. Mariner is designed to address that deficiency by starting Xarelto treatment only after standard Enoxaparan treatment is halted at discharge. Xarelto will be superior to placebo in terms of efficacy and inferior in terms of safety (bleeding). The question is one of net benefit. Mariner might make its primary endpoint.
How will this affect Betrixaban sales. The decision to start Betrixaban comes at the point of hospitalization. The decision point for Xarelto would be at discharge. The efficacy comparison for physicians would be comparing Betrixaban to Enoxaparan followed by Xarelto at discharge. Cross trial comparisons are always difficult, but this is one that I think Betrixaban wins on the basis of safety. Xarelto failed Magellan because it was of similar efficacy to enoxaparin and clearly less safe. Betrixaban succeeded in Apex because it was similar to enoxaparin in terms of safety and clearly superior on the efficacy side. Which regimen would you prefer if your were the patient?
Remember Mariner was designed to fix Magellan, not to compete with the Apex result. If given the chance to rethink Mariner with advance knowledge that Betrixaban would be approved, I doubt that JnJ would have spent the money to run the trial.