FDA Advisors Say No Cardiovascular Outcomes Studies Needed for Opioid Receptor Antagonists
Movantik (naloxegol oxalate) set for September review
By a majority vote, the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) has concluded that the agency should not require cardiovascular outcomes trials for the peripherally acting mu-opioid receptor antagonist (PAMORA) class of drugs, which includes Movantik (naloxegol oxalate, AstraZeneca), an investigational treatment for opioid-induced constipation (OIC) in patients with chronic non-cancer pain.
Following a clarification of the vote, the committee suggested continued post-approval data collection for cardiovascular safety.
The FDA convened a meeting of the AADPAC to review the PAMORA class on June 11–12, 2014. The meeting assessed the necessity, timing, design, and size of cardiovascular outcomes trials to support the approval of products in that class for the proposed indication of OIC in patients taking opioids for chronic non-cancer pain.
The FDA is not bound by its advisors’ recommendations, but takes their advice into consideration when reviewing applications for investigational medications.
The Prescription Drug User Fee Act (PDUFA) date for Movantik is September 16, 2014. If approved, the drug would be the first once-daily oral PAMORA for the treatment of OIC in patients with chronic non-cancer pain.
Opioids play an important role in chronic pain relief by binding mu-receptors in the brain, but they also bind mu-receptors in the bowel. That is why patients taking opioids for chronic pain can develop OIC. In fact, the incidence of OIC can be as high as 81% in patients taking opioids.
An estimated 235 million prescriptions for opioids are written in the U.S. each year, of which 20% are for chronic pain. For patients taking prescription opioids for chronic pain, constipation is a common side effect, one not adequately relieved by laxatives.
On June 4, 2014, the New England Journal of Medicine published data online from two pivotal phase III studies of Movantik: KODIAC-4 and KODIAC-5. Both studies met their primary efficacy endpoint, demonstrating an improvement in treatment effect versus placebo. More OIC patients with non-cancer pain treated with Movantik 25 mg showed a consistent response of increased spontaneous bowel movements through 12 weeks of treatment compared with patients given placebo.
Movantik (naloxegol oxalate) is an investigational PAMORA designed for the treatment of OIC in patients with chronic non-cancer pain. The drug specifically blocks the binding of opioids to opioid receptors in the gastrointestinal tract without affecting opioid receptors in the brain.
Source: AstraZeneca; June 12, 2104.