During a press briefing, David R. Gastfriend, MD, vice president of scientific communications for Alkermes, announced that a supplemental new drug application for extended-release injectable naltrexone had been designated a priority review by the FDA. An action date is set for October 12, 2010. Four years ago, the FDA approved the medication for the treatment of alcohol(Drug information on alcohol) dependence.
Gastfriend presented results from a 6-month, multicenter, phase 3 clinical trial on the safety and efficacy of extended-release injectable naltrexone (listed in the study as XR-NTX) for opioid dependence.1
Opioid dependence is a growing public health crisis, according to Gastfriend, a one-time addiction researcher and treatment provider at Massachusetts General Hospital and Harvard Medical School, Boston.
According to the 2008 US National Survey on Drug Use and Health, 282,000 individuals 12 years and older are dependent on or are abusing heroin, and 1.7 million are dependent on or are abusing prescription pain relievers. In addition, a recent study found that hospitalizations caused by accidental and intentional abuse of prescription painkillers as well as sedatives and tranquilizers have risen dramatically during the past decade.2 Comparatively, methadone(Drug information on methadone) use accounted for the largest relative leap in hospitalizations, rising 400% between 1999 and 2006.
The most common approach to treating opioid dependence, Gastfriend said, is substitution therapy—agonist medications, such as methadone and buprenorphine(Drug information on buprenorphine) that bind to the brain’s opioid receptors and mimic the action of opioids to varying extents, “so the treatments themselves can be dependency-producing,” he added.
In contrast, naltrexone is an opioid antagonist, which prevents opioids from binding to receptor sites. Besides being nonaddictive, Gastfriend said the once-monthly intramuscular injection of naltrexone helps resolve adherence issues.
XR-NTX was developed with support from the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, in part because of challenges related to oral medication administration.
The phase 3 study conducted in Russia involved 250 adults who had completed up to 30 days of inpatient treatment for opioid detoxification and had not been taking any opioids, including buprenorphine and methadone, for at least 7 days. Patients were randomized to 24 weeks of treatment with either 380 mg of XR-NTX given by intramuscular injection (n = 126) or placebo injection (n = 124). All patients received individual drug counseling.
“We found that extended-release naltrexone was generally safe and well-tolerated with no discontinuation due to adverse events,” Gastfriend said.
The most common clinical adverse events experienced by patients receiving XR-NTX during the study were nasopharyngitis and insomnia.
The trial’s primary efficacy end point was the response profile based on the rate of urine drug screens that were free of opioids during the last 20 weeks of the 24-week double-blind treatment period, as measured by the cumulative distribution of the opioid-free urine screens.
Gastfriend noted that patients treated once monthly with XR-NTX demonstrated statistically significant higher rates of opioid-free urine screens compared with patients treated with placebo (P < .0002). After 24 weeks, the median percentage of opioid-free urine screens was 90% among patients taking XR-NTX, compared with 35% among patients taking placebo.
The trial also showed differences in 4 secondary efficacy end points, which included study retention rate, scores on a visual analogue scale of craving, self-reported opioid use, and physiological evidence of opioid dependence on naloxone(Drug information on naloxone) challenge.
“These end points were clinically meaningful,” Gastfriend emphasized. “For example, patients on placebo continued to crave opioids throughout the study at the same level they started with at baseline. In contrast, the patients on extended-release naltrexone had a rapid decline in craving to half their baseline level and that was maintained throughout the study.”
The phase 3 trial is being continued in an additional yearlong open-label safety study, Gastfriend said, but the company does not yet have data on the follow-up.
