WASHINGTON -- A nasal-spray formulation of desmopressin for nocturia received consistent, if sometimes tepid, support from an FDA advisory committee.
At the conclusion of a day-long hearing, the Bone, Reproductive, and Urologic Drugs Advisory Committee decided by a 14-4 margin that the sponsor, Serenity Pharmaceuticals, had demonstrated that the benefits of the treatment outweighed potential risks. However, even the panelists who voted in the affirmative expressed reservations about a number of issues, ranging from clinical trial design to episodes of hyponatremia linked to the drug to uncertainty about the most appropriate indication.
"I reluctantly voted yes," said Kevin McBryde, MD, of the National Institute of Diabetes and Digestive and Kidney Diseases. "I think the incidence of hyponatremia was low ... I think the difference of about 120 mL of urine output between the placebo and the 1.5 microgram (desmopressin) group is enough that over the course of the night it saves them some nocturnal awakenings."
Douglas C. Bauer, MD, of the University of California San Francisco, voted no but then acknowledged, "I thought was voting on the broad indication of nocturia [as opposed to nocturnal polyuria], so I agree with what many of the 'yes' people have said."
Bauer added, "I think there are rare, serious side effects that will be magnified greatly if this is used in nonspecialist hands and applied to a very large number of patients, particularly those who are elderly and at highest risk."
Committee chair Vivian Lewis, MD, of the University of Rochester, voted yes but emphasized that the drug's indication should be limited to the diagnosis of nocturnal polyuria, rather than nocturia, which is a symptom. However, other members of the panel pointed out that clinical trial support for application evaluated the drug for treatment of nocturia. Evidence submitted in support of the application came from a randomized, placebo-controlled evaluation of two doses of desmopressin in a total of 782 patients with nocturia (0.75 and 1.5 mcg). As reported earlier this year at the American Urological Association meeting, both doses of desmopressin reduced episodes of nocturia compared with placebo. However, only the higher dose was associated with a significantly higher response rate.
Before affirming that the drug's benefits outweighed the risks, the panel agreed by a 17-1 vote that the 1.5 mcg dose of nasal spray desmopressin had demonstrated efficacy but not the 0.75 dose.