This month, the FDA's Advisory Committee responsible for cardiovascular and renal drugs recommended against approval of ximelagatran (Exanta, AstraZeneca,) a drug developed as a substitute for coumadin. Its major advantage over coumadin was the ability to use the new drug in a standard dosage, without needing to do frequent blood tests and dosage adjustments. ( Read about ximelagatran here.)
Early studies had shown the drug to be effective and apparently safe, and when the panel met, apparently members had hoped to vote for approval. However, as the data related to ximelagatran was presented, the incidence of liver toxicity seen with this drug was revealed for the first time. Mild liver dysfunction had been noted in earlier reviews of the data, but until the FDA panel met, long-term results with ximelagatran had not been publicly reviewed. These data revealed that 1 in 200 patients treated long-term with the drug had severe liver injury, and about 1 in 2000 died. Further, there was evidence that patients treated with ximelagatran also had an increased risk of heart attack.
Given this new evidence, the panel - very reluctantly - voted not to approve the drug.
The ultimate fate of ximelagatran is yet to be determined. It is still possible the drug could be successfully labeled for short-term use in selected patients. But it seems clear that the hoped-for use of this new drug - as a widely available and widely used substitute for coumadin - is simply not going to happen.
Other drugs are being developed as a coumadin substitute, but safety and efficacy studies for these substances are in a much earlier stage, and no one can say whether one of them will eventually get us across the goal line. For now, we're stuck with the inconvenience of coumadin.
