New drug approved by FDA for treatment of opioid-induced constipation

FDA has approved a new treatment option for opioid-induced constipation in adult patients with chronic noncancer pain. Naloxegol (Movantik, AstraZeneca) tablets C-II is the first once-daily, oral, peripherally acting µ-opioid receptor antagonist (PAMORA) to be approved for this condition.

As part of the PAMORA class of drugs, naloxegol is used to decrease the constipating effects of opioids. Approximately 40% to 80% of those receiving long-term opioid therapy experience opioid-induced constipation.

Opioids help provide chronic pain relief by binding µ-opioid receptors in the brain, but as the drugs also bind µ-receptors in the gastrointestinal (GI) tract, the associated side effect of reduced motility in the GI tract can occur. This leads to infrequent bowel movements and difficulty passing stools or evacuating bowels. Naloxegol has been designed to block the binding of opioids to opioid receptors in the GI tract while not impacting the opioid receptors in the brain.

“We are pleased to provide physicians and their patients with a once-daily oral treatment supported by a robust clinical program,” said Dr Briggs Morrison, the executive vice president for global medicines development and the chief medical officer of AstraZeneca.

Two multicenter, randomized, placebo-controlled phase 3 clinical trials provided the data on the safety and effectiveness of naloxegol. Study participants included 1352 outpatients with noncancer related pain who had received opioids for >4 weeks and had opioid-induced constipation.

Subjects were randomized to groups receiving 12.5 mg or 25 mg of naloxegol, or placebo once daily for a total of 12 weeks. The 12-week response rate (>3 spontaneous bowel movements [SBMs] per week and an increase from baseline >1 SBM for >9 of 12 weeks and for >3 of the last 4 weeks) was the primary endpoint.

Patients receiving naloxegol 25 mg had significantly higher response rates than did those receiving placebo. In the first trial, 44% receiving naloxegol 25 mg compared with 29% on placebo had increased SBMs per week (P=.001). Results were similar in the second trial (40% vs 29%; P=0.02). For patients in the first trial on the 12.5 mg dose, 41% had increased SBMs versus 29% on placebo (P=0.02). Statistical significance was not demonstrated with this dose in the second trial.

Although adverse events with the use of naloxegol mostly concern the GI tract, a postmarketing study is being required by FDA to ascertain the risk of adverse cardiovascular events in patients who have been prescribed naloxegol.

It is anticipated that naloxegol will be on the market in the first half of 2015. The drug is also under regulatory review by the European Medicines Agency and in Canada.