Over at the Atlantic this week, an article was published written by one of the people who took part in the early trials of tolvaptan for APKD. The article shows just how much hope people with this disorder were putting on this drug and the disappointment felt in the APKD community now that the FDA has rejected its use for this indication. Given the lack of new therapies that are available for renal diseases in general it is understandable that patients and their doctors are unhappy with this decision.
However, it should be said that there are substantial questions that remain to be answered about the use of this drug. The large trial published in the NEJM last year showed that tolvaptan reduced the rate of growth in kidney size while also leading to a slowdown in the rate of GFR decline. However, these are surrogate endpoints and we have been burned by surrogate endpoints in nephrology before (see Bardoxolone). Also, the majority of patients had good renal function at baseline. Not all patients with PCKD will develop ESRD and there is no indication at this time who should be treated with this drug and for how long. It should also be said that there was a high rate adverse events in the treatment group (primarily related to thirst and polyuria) and 23% of participants discontinued the drug. It is extremely expensive and it is important that there are clear guidelines for its use. As mentioned in this pos t, copeptin levels may be useful in determining who will respond to tolvaptan.
That said, it is always interesting and revealing to know the patient's point of view on this difficult issues.