January 9th, 2015

FDA Approves New Oral Anticoagulant from Daiichi Sankyo

And then there were four.

Late Thursday the FDA announced that it had approved edoxaban, the new oral anticoagulant manufactured by Daiichi Sankyo. The drug will be marketed under the brand name of Savaysa and joins three other new drugs in the large and important new oral anticoagulant marketplace: dabigatran (Pradaxa), rivaroxaban (Xarelto), and apixaban (Eliquis). All four drugs were designed to overcome the limitations of warfarin, which has long been available as an inexpensive generic drug but which requires extensive monitoring and dose adjustment and has numerous interactions with other drugs and foods.

The FDA approved two indications for edoxaban: for reducing the risk of stroke in patients who have non-valvular atrial fibrillation (AF) and for treating deep vein thrombosis and pulmonary embolism in patients who have already been receiving an anticoagulant by injection or by infusion for 5 to 10 days.

Last October the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 9-1 in favor of approval for the AF indication. But the positive vote did not fully reflect the panel’s concerns about the drug, which centered on a troubling subgroup analysis in the otherwise positive Engage AF-TIMI 48 trial. This analysis suggested that the benefit associated with edoxaban occurred exclusively in the large group of patients with impaired renal function (and, therefore, presumably, higher circulating levels of the drug). There was a trend suggesting that edoxaban was harmful in the subgroup of patients with normal renal function. Although subgroup analysis is often tricky, both the FDA reviewers and panel members felt that this was a biologically plausible phenomenon that could have important clinical implications.

As a result of this finding, edoxaban will contain a boxed warning that the drug is less effective in AF patients with a creatinine clearance greater than 95 ml/min. Physicians should measure creatinine clearance before initiating treatment with edoxaban. People with creatinine clearance levels over 95 ml/min should receive a different anticoagulant.

Bleeding is the most serious side effect of edoxaban, as with all anticoagulants. Currently there is no treatment that has been shown to reverse the anticoagulant effect of the drug. Premature discontinuation of edoxaban increases the risk of stroke.


3 Responses to “FDA Approves New Oral Anticoagulant from Daiichi Sankyo”

  1. Cassandra Harrison, MD says:

    I’ve never heard of a drug being more harmful in pt’s with creatinine clearance >95. Is this a typo in your above abstract?

    • Dr. Harrison– at the advisory panel in October the FDA analysis found that stroke reduction in patients with renal impairment (and therefore higher circulating levels of the drug) was highly significant while there was a trend toward harm in the group with normal renal function. Does that answer your question?

  2. David Powell , MD, FACC says:

    As you recall, the FDA surprisingly approved dabigatran at a lower “renal” dose never clinically tested. Were they not able to derive a higher dose effective with normal renal function from available pharmokinetic data, or did they opt out of such creativity?
    I do not think usual GFR formulas are that accurate in the “normal” range. Hence, I am skeptical for GFR> 60.