Clinical Trials Likely to Be Focal Point in Xarelto Lawsuits

Clinical TrialsDrugs

Although the legal strategy of Xarelto plaintiff attorneys won’t become clear until the first trials begin in early 2017, it appears that the quality—or seeming lack thereof—of clinical trials used to approve Xarelto (rivaroxaban) will be a key issue. One particular point of emphasis could be a lack of quality data supporting once-daily Xarelto dosing, something drugmakers Bayer/Janssen claim makes Xarelto more convenient but could cause life-threatening side effects.

Xarelto’s once-daily dosing makes the blood thinner more convenient, but could also make it more dangerous.

Xarelto and other so-called “novel anticoagulants” are vying to replace the older blood thinner Coumadin (warfarin) largely on the grounds that they are easier to use than warfarin. Blood thinners are prescribed to patients at risk for developing blood clots and suffering related complications such as stroke and deep vein thrombosis.

Xarelto does not require medical monitoring to ensure patient safety, whereas warfarin patients must be monitored once or twice per month for blood clot risks and have their dosage adjusted accordingly. Another purported benefit of Xarelto over warfarin is its once-daily dosing, something that makes Xarelto more user-friendly—and thus more marketable—but according to some critics makes the drug more dangerous.

Xarelto’s Short Half-Life

The dosing problem has to do with Xarelto’s relatively short half-life of 5-9 hours. Other new coagulants such as Pradaxa and Eliquis have a half-life of 12-17 hours, while warfarin has a half-life of 20-60 hours.

A short half-life means that a drug’s concentration in the body diminishes rather quickly. This leads to drug “peaks” (high drug concentrations) and “troughs” (low drug concentrations). Fluctuations in drug concentration present a twofold risk: of bleeding (when concentrations are high), and of lower blood clot prevention efficacy (when concentrations are low).

According to one study, at its peak the amount of Xarelto measured in the blood was 16.9 times higher than at its trough. For Eliquis (abixaban), which is administered twice per day, the peak was 4.7 times higher than the trough.

FDA staff clearly identified this issue during the approval process but decided to clear Xarelto for sale because clinical trial data indicated it had a safety profile that was no worse than warfarin.

But while the overall safety of the drugs was comparable in premarketing studies, postmarketing adverse event data shows what would be expected of a drug with a short half-life and once-daily dosing. According to data provided by the Institute for Safe Medication Practices (ISMP), compared to other blood thinners, Xarelto has a significantly higher frequency of treatment failure events (embolic-thrombotic events, or blood clot events), an apparent outcome of a “trough.”

Potential side effects of rivaroxaban “peaks,” which may lead to excessive levels of the drug in some patients’ bodies,  are especially concerning when considered alongside Xarelto’s lack of a reversal agent. Plaintiffs in Xarelto lawsuits commonly claim that they were not properly warned about the lack of a Xarelto bleeding antidote. If serious bleeding occurs with warfarin, the drug’s effect is easily reversible.

Bad Dosing Data

FDA reviewers noted that the “the clinical relevance was uncertain” in regards to the safety profile of Xarelto 10 mg twice daily versus Xarelto 20 mg once daily. The reason for their uncertainty? In the pivotal trial (ROCKET AF study) used to support Xarelto’s approval, only the once-a-day regimen was tested.

One study did compare once daily dosing with twice daily dosing, but according to an attorney representing Xarelto lawsuit plaintiffs, the study was on par with “an elementary school science fair project” due to numerous shortcomings, including missing data.

One attorney compared Xarelto clinical trials to “an elementary school science fair project.”

An article published in the Journal of the American College of Cardiology reviewed the trial-in-question (the ATLAS ACS 2–TIMI 51 Trial) and found that “an unanticipated high rate of missing data, particularly the vital status of patients, precludes reliable and valid information.” The article also found that “there was a lack of an expected dose response—the 5-mg dose did not have greater efficacy compared with the 2.5-mg dose of rivaroxaban.”

So why, in spite of inadequate safety and efficacy data, is Xarelto recommended for once-daily dosing? It could simply be a marketing ploy. Once-a-day dosing helps to sell the idea that Xarelto is more convenient than competitors.

If plaintiff attorneys are able to poke holes in Xarelto clinical trials and show that Bayer/Janssen should have provided stronger warnings about the potential side effects associated with once-daily dosing, they may have success in the initial Xarelto trials that are scheduled for February and March 2017.

Questions about Xarelto litigation? Interested in filing a claim? Get in touch with and learn your legal options.

Free Case Review

(Sources: ISMP Quarter Watch; FDA; JACC; PennRecord)