The proposed dosing for a drug being developed by Allergan Plc to treat frequent urination at night has not been adequately studied in trials, a preliminary review by the U.S. Food and Drug Administration staff concluded.
The drug, SER120, is a low-dose nasal version of the commonly used treatment, desmopressin, and is designed to treat adults with nocturia, a disorder where a person wakes up to urinate twice or more at night.
There are no FDA-approved drugs to specifically treat nocturia.
Allergan has proposed starting patients with a 0.75 microgram (mcg) dose, and moving up to 1.5 mcg if necessary, but this dosing regimen was not studied in any clinical trials, staff reviewers said on Monday. (bit.ly/2dIxcrs)
In addition, late-stage data showed that only the higher dose met the statistical criteria for efficacy. The "clinical meaningfulness" of the drug's benefit was also unclear when compared with a placebo, the reviewers said.
Desmopressin was first approved in the United States in 1978 to treat patients with diabetes insipidus, a rare disorder that causes an imbalance of water in the body.
Since then, the FDA has sanctioned the drug's use in other conditions.
An oral desmopressin pill from privately held Ferring Pharmaceuticals has been rejected twice by the FDA, which said the risk of hyponatremia, or abnormally low sodium levels in the blood, outweighed the drug's benefit.
The FDA had asked Allergan to enroll patients aged at least 50 to better assess the risk of hyponatremia, which is greater in the elderly, in its late-stage trials for SER120.
However, since the company is seeking approval for adults regardless of age, efficacy in patients younger than 50 has not been assessed, the staff said.
Of the five deaths among patients on SER120 during clinical trials, the role of the drug cannot be definitively ruled out in two, the reviewers said.
Four of the five deaths were in patients older than 75.
Nocturia is a considered a symptom of one or more underlying conditions such as obstructive sleep apnea, diabetes mellitus and congestive heart failure.
The review comes two days ahead of a meeting of outside experts who will recommend to the FDA whether to approve the drug.
The agency is not obliged to follow its advisory panel's recommendations but typically does so.
Allergan in 2010 acquired from privately held Serenity Pharmaceuticals exclusive rights to develop, manufacture and sell the drug for all potential indications, excluding bedwetting in children.
The company's shares were down 1.3 percent at $224.42 in morning trading.
(Reporting by Natalie Grover in Bengaluru and Toni Clarke in Washington; Editing by Sriraj Kalluvila)