Dive Brief:
- Results from two studies of Johnson & Johnson and Bayer's anticoagulant Xarelto failed to show sought-after benefits, falling short of trial goals and, in the process, weighing on the drugmakers' efforts to expand use of the drug.
- In the first, dubbed MARINER, Xarelto did not significantly reduce the risk of a composite endpoint of symptomatic venous thromboembolism (VTE) or VTE-related death versus placebo. Data from the second, known as COMMANDER HF, showed Xarelto to have no significant benefit on death from any cause, heart attack or stroke compared to placebo.
- Undaunted, J&J said it will still pursue a filing with U.S. regulators for Xarelto in preventing blood clots among acute medically ill patients following a hospital discharge, relying on a previous data set as well as MARINER.
Correction: A previous version of this article misidentified the developer of Pradaxa
Dive Insight:
Although sales of direct-acting anticoagulants like Xarelto (rivaroxaban) have climbed, these drugs have yet to unseat warfarin, the cheaper and often-prescribed blood thinner considered the standard of care.
Even five years after the approval of DOACs, warfarin still holds a slight edge in prescription share. As a result, drugmakers have turned to post-marketing studies to help expand the use of their products into new clinical settings.
In the MARINER trial, the use of Xarelto was studied across 45 days after hospitalized patients were discharged. Although Xarelto showed no statistically significant effect on risk of VTE-related death, it was associated with fewer symptomatic VTE events than placebo, investigators said.
With the MARINER study and an earlier trial called MAGELLAN, J&J's research unit Janssen had hoped to show the benefits to once-daily Xarelto for recently released hospitalized patients — a move that could expand the patient population of the drug. MAGELLAN results were more positive than those of MARINER, and showed Xarelto to be non-inferior to the Lovenox in short-term use over approximately 10 days among acutely ill patients released from the hospital.
Taking the results of both together, J&J said it will initiate talks with the FDA about the most appropriate acutely ill patients to receive Xarelto both in the hospital and after discharge, according to a press release. Patients who are hospitalized for acute medical illness remain at risk for VTE six weeks or more after discharge, but the role of extended prophylaxis with blood thinners remains controversial.
The COMMANDER study, meanwhile, compared the use of Xarelto against placebo on top of standard of care in 5,000 heart failure patients who recently experienced an episode of acute decompensated heart failure. Data unveiled Monday failed to show any difference between the two arms of the study in its primary endpoint, a composite of heart attack, stroke and all-cause death.
Results from MARINER and COMMANDER were announced at the European Society of Cardiology (ESC) Congress 2018 and published in the New England Journal of Medicine.
Meanwhile, Bristol-Myers Squibb is further studying Eliquis (apixaban), its anticoagulant rival to Xarelto, building a case through real-world evidence and post-marketing studies.
Right now, Eliquis leads Xarelto in new prescriptions, according to data from Iqvia cited by investment bank Cowen & Co. J&J is looking to change that, but the data from ESC might not provide the desired boost. Pradaxa (dabigatran), a third option marketed by Boehringer Ingelheim, is a distant third.