Tolvaptan and lixivaptan: what’s the difference?

In response to the news about lixivaptan’s orphan drug designation, there have been questions from the PKD community about the difference between the investigational drug and another potential ADPKD treatment, tolvaptan.

Tolvaptan and lixivaptan are vasopressin V2 receptor antagonists, meaning that they block the vasopressin receptor on kidney tubules, and more importantly on cells lining the cysts in PKD.

In normal kidneys, vasopressin acts to concentrate the urine and preserve body water. The effect of these drugs in cysts is to inhibit proliferation of cells lining the cysts and secretion of fluid into the cysts that occur in response to vasopressin. This means that the cysts will grow more slowly when vasopressin is blocked.

Tolvaptan and lixivaptan are similar in structure, but they are not identical. These differences in structure may mean that the drugs may differ in how well they work and how safe they are. These differences will be determined by comparing the results of clinical trials. It is even possible these two drugs could be compared head to head, but that is up to the drug companies.

The FDA will work closely with the developer of lixivaptan because of its orphan drug designation. We are encouraged by this and the fact that more drug companies are interested in developing new therapeutics for PKD.

David Baron

David Baron, Chief Scientific Officer