HYATTSVILLE, MD. – The majority of a Food and Drug Administration advisory panel voted against approval of an orally disintegrating sublingual tablet formulation of desmopressin as a treatment for nocturia, citing uncertainties about the clinical benefits in the pivotal trials and concerns about the risk of hyponatremia.
At the meeting on Jan. 12, the FDA Endocrinologic and Metabolic Drugs Advisory Committee voted 10 to 5, with two abstentions, that the benefits of this desmopressin formulation in clinical trials did not outweigh the risks for the proposed indication, the treatment of nocturia due to nocturnal polyuria in adults who wake up two or more times each night to void. The indication proposed by Ferring Pharmaceuticals includes the statement that prior to treatment, “lifestyle changes and other treatable medical causes of nocturia should be addressed.”
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Although the panel agreed that treatment was associated with statistically significant effects on the two primary endpoints in the two pivotal trials, those voting against approval said there were uncertainties about the clinical benefits, which several panelists said could be addressed in preapproval studies.
The panel generally agreed that the studies demonstrated a low risk of hyponatremia, the main safety concern associated with treatment. But they said that it was unclear whether the appropriate patients would be selected for treatment and would be properly monitored as recommended during treatment in real-world clinical situations. Examples included whether patients would remember to stop taking the medication when they developed an illness that could increase their risk of hyponatremia, or if they developed a disease or condition that affects sodium as they got older. There was also some uncertainty over the clinical significance of the small decreases in serum sodium in patients during the course of the 3-month studies, which evaluated two gender-specific doses that were lower than the higher doses previously studied that were associated with an increased risk of hyponatremia.