FDA Okays Naldemedine (Symproic) for Opioid Constipation

Pauline Anderson

March 29, 2017

The US Food and Drug Administration (FDA) has approved naldemedine (Symproic) for the treatment of opioid-induced constipation (OIC) in adult patients with chronic noncancer pain, Shionogi Inc and Purdue Pharma LP have announced.

The product is a once-daily oral peripherally acting mu opioid receptor antagonist.

The agent is currently a Schedule II controlled substance because it is structurally related to naltrexone. Shionogi has submitted a petition for the de-scheduling of the drug, or removal of the controlled substance classification, to the US Drug Enforcement Administration, which is currently under evaluation.

Approval was based on data from the COMPOSE global development program comprising clinical studies conducted in adult patients with OIC and chronic noncancer pain.

The program included three studies: COMPOSE I and COMPOSE II, both 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies, and COMPOSE III, a 52-week, randomized, double-blind, placebo-controlled, long-term safety study.

According to background information provided by the companies, constipation is one of the most commonly reported side effects associated with opioid treatment. It may occur when opioids bind to mu opioid receptors in the gastrointestinal tract.

OIC is defined as a change in bowel habits characterized by any of the following after initiating opioid therapy: reduced bowel movement frequency, development or worsening of straining to pass bowel movements, a sense of incomplete rectal evacuation, or harder stool consistency.

In patients with chronic noncancer pain, the prevalence of OIC ranges from 40% to 50%. In one survey of 322 patients taking daily opioids for chronic pain, 33% of patients missed, decreased, or stopped opioid use to ease bowel movements.

The most common adverse reactions experienced by patients receiving treatment compared with placebo in clinical trials were abdominal pain (8% vs 2%), diarrhea (7% vs 2%), nausea (4% vs 2%), and gastroenteritis (2% vs 1%).

Symproic in 0.2-mg tablets will be jointly launched in the United States by Shionogi Inc and Purdue Pharma LP and is expected to be commercially available mid-summer 2017.

Several other constipation drugs have been launched recently. The FDA approved an oral formulation of methylnaltrexone bromide (Relistor, Valeant Pharmaceuticals International Inc/Progenics Pharmaceuticals Inc) for OIC in adults with chronic noncancer pain in July 2016. 

In January 2017, the FDA approved plecanatide for chronic idiopathic constipation (CIC) in adults. Plecanatide (Trulance, Synergy Pharmaceuticals), a once-daily oral medication, works locally in the upper gastrointestinal tract to stimulate secretion of intestinal fluid and support regular bowel function, according to the FDA.

Also in January, Ironwood Pharmaceuticals and Allergan jointly announced that linaclotide (Linzess) is now available in 72-μg capsules for the treatment of adults with CIC. The new dose will provide physicians with "dosing flexibility based on individual presentation or tolerability, in treating the large and heterogenous population of adult CIC patients," the companies said in a news release.

In 2014, the FDA approved naloxegol (Movantik, Astra Zeneca Pharmaceuticals), a mu opioid receptor antagonist, for the treatment of OIC in adults with chronic noncancer pain.

"The FDA approval of Symproic provides a safe and effective therapy for adult patients suffering from chronic non-cancer pain and struggling with opioid-induced constipation," said John Keller, president and chief executive officer, Shionogi Inc, in the press release.

"By entering this exciting new therapeutic area with Shionogi Inc, we have the opportunity to further help patients with chronic non-cancer pain by offering more comprehensive care to both patients and doctors," commented Mark Timney, president and chief executive officer, Purdue Pharma LP.

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