FDA Panel Expresses Concerns Over Allergan-Serenity Drug for Nighttime Urination

October 18, 2016
By Mark Terry, BioSpace.com Breaking News Staff

The U.S. Food and Drug Administration (FDA) has raised concerns in a preliminary review regarding appropriate dosing for Dublin-based Allergan ’s SER120. SER120 is a low-dose nasal formulation of desmopressin designed to treat adults with nocturia. Nocturia is when an individual wakes up to urinate twice or more at night.

Currently there are no drugs approved by the FDA for nocturia.

The FDA convened an advisory panel to discuss SER120, which was submitted by Serenity Pharmaceuticals. Serenity and Allergan inked the collaboration deal in April 2010. The proposed initial dose was 0.75 mcg (one nasal spray) 30 minutes prior to bedtime. If needed, it could be increased to 1.5 mcg (two nasal sprays) nightly. Desmopressin is a synthetic analog of the antidiuretic hormone vasopressin. It stimulates reabsorption of water in the kidney, which leads to more concentrated urine.

There are several desmopressin formulations, including as a nasal spray, on the market for central diabetes insipidus, primary nocturnal enuresis in children, and to maintain hemostasis in von Willebrand’s Disease and Hemophilia A patients during surgery.

Allergan and Serenity conducted two Phase III trials in support of the dosing regimen, which were restricted to patients 50 years of age or older. The FDA, while the trial protocols were being developed, advised the companies to limit enrollment to this group to better assess the risk of hyponatremia. Hyponatremia is a very low level of sodium in the blood, a common side effect of desmopressin.

The trials showed that only the higher dose met the efficacy criteria. The reviewers also indicated that the drug’s benefit compared to placebo was unclear.

Another company, Ferring Pharmaceuticals, has tried to get the FDA to approve its oral desmopressin pill, but has been rejected twice because of the risk of hyponatremia.

There were five deaths during the trials, although the connection to the drug has not been proven. The FDA panel stated, “Four of the deaths occurred in subjects who were older than 75 years of age. A role of SER120 in the deaths due to cecal perforation, coronary atherosclerosis, and bleeding aortic aneurysm is unlikely; a role cannot be definitively ruled out for the other two deaths.”

The bottom line of the advisory panel appears to be that the proposed dosing hasn’t been adequately studied. The advisory report came out two days before another meeting of outside experts, October 19, who will make a recommendation on whether the FDA should approve the drug. The FDA is not required to follow the advisory panel’s recommendations, even though that is often the case.

In the original 2010 agreement, Allergan picked up exclusive worldwide rights to develop, manufacture and commercialize SER120. It covered all possible indications except Primary Nocturnal Enuresis (pediatric bedwetting). Allergan paid Serenity $43 million upfront and there were potential development and regulatory milestone payments of up to $122 million. If the drug is approved, there are also potential sales milestones and royalty payments.