Alkermes Reports Study on ER Naltrexone in Opioid-Dependent Patients Involved in Criminal Justice System Publised in NEJoM

Results from a study published this week in the New England Journal of Medicine (NEJM) demonstrated the utility of extended-release naltrexone (VIVITROL®) in individuals involved in the criminal justice system. VIVITROL is Alkermes' ALKS once-monthly, non-narcotic medication for the prevention of relapse to opioid dependence, following opioid detoxification. The open-label, randomized, controlled, effectiveness trial compared six monthly injections of extended-release naltrexone with usual treatment (brief counseling and referrals for community treatment programs, including the option of agonist therapies) for the prevention of opioid relapse among criminal justice offenders. In the study, extended-release naltrexone showed a statistically significant reduction in relapse rates (p<0.001) and, for those who relapsed, a significantly longer median time to relapse compared with the usual-treatment group in the six-month treatment period (p<0.001). Overall, more participants reported adverse events in the extended-release naltrexone group versus those in the usual-treatment group, whereas the rate of serious adverse events was significantly lower in the extended-release naltrexone group, compared with the usual-treatment group (p=0.006). Reflective of the growing public health concern of opioid addiction and its impact on the criminal justice system, the study, entitled "Extended-Release Naltrexone to Prevent Opioid Relapse in Criminal Justice Offenders,"1 was sponsored by the National Institute on Drug Abuse (NIDA) and was led by 17 clinical researchers and addiction specialists throughout the U.S. The study's lead author is Joshua D. Lee, M.D., M.Sc., associate professor in the departments of Population Health and Medicine at NYU Langone Medical Center, and the senior author is Charles O'Brien, M.D., Ph.D., vice chair of Psychiatry at the Perelman School of Medicine at the University of Pennsylvania and founding director of Penn's Center for Studies of Addiction. Approximately one-third of heroin users pass through correctional facilities annually in the U.S.2 Nearly 65 percent of the 2.3 million U.S. prison inmates meet the medical criteria for substance abuse or addiction, yet only 11 percent receive treatment during their incarceration.3 In addition, more than half of those on parole or probation continue to go untreated.4 "The opioid epidemic has put a growing strain on our criminal justice system where individuals struggling with opioid addiction are in need of treatment. Since our prisons and criminal justice system are among the largest providers of addiction services in the country, it is critical that we expand the range of medication treatment options available to this population and connect people to community-based treatment programs," commented Sheriff James M. Cummings of Barnstable County, Mass. "In Barnstable, we've had success with VIVITROL as an important component of our program, which also includes counseling and other support services essential for individuals to successfully recover and re-enter the community. VIVITROL may play an important role in the criminal justice system, as it is a long-acting, non-narcotic, non-addictive opioid antagonist with no known abuse or diversion potential." This NIDA-sponsored study began in 2009, prior to the approval of extended-release naltrexone for the treatment of opioid dependence. Consequently, as noted by the authors, extended-release naltrexone was not widely available to the public sector community during the treatment period. Today, extended-release naltrexone is being used in the criminal justice setting in more than 100 pilot programs throughout 30 states, including drug court, criminal justice re-entry, legislative and public health initiatives. Each of these programs is designed with various medication treatment parameters, psychosocial support and differing scopes of surrounding community support services. "It is encouraging to see data showing, in comparison with a traditional treatment approach, VIVITROL helped to reduce relapse to opioid dependence and protected against overdoses in this patient population. It is also reassuring to see that the frequency of overdoses in patients treated with VIVITROL did not increase after the medication was discontinued," stated Adam Bisaga, M.D., Professor of Psychiatry at the Columbia University Medical Center and Research Scientist at the New York State Psychiatric Institute. "Opioid dependence is a chronic disease that requires an individualized treatment plan, including psychosocial treatments and a medication support, along with monitoring that should extend over the long term to assure the best possible clinical outcome." Results of Study Published in NEJM The study compared the use of extended-release naltrexone versus usual treatment in more than 300 criminal justice offenders at five sites.5 During the six-month treatment period of the open-label study, participants were randomized to two arms: one receiving extended-release naltrexone once monthly and the other receiving usual treatment (brief counseling and referrals for community treatment programs, including the option of agonist therapies) without extended-release naltrexone. The lead investigators of the study made an independent determination to select a six-month treatment period for study participants, followed by discontinuation of extended-release naltrexone in the treatment group and provision of referrals to local community treatment programs to all study participants. In addition to referrals, participants received brief counseling and the option of agonist therapies. Thirty-seven percent of the usual-treatment group pursued agonist treatments, primarily after resumed illicit opioid use and relapse, during the trial. Data from the study showed that the median time to relapse, the primary endpoint, was more than two times longer, among those who relapsed, in participants randomized to extended-release naltrexone, compared with usual treatment (p<0.001). The usual-treatment group experienced nearly 50 percent more relapse events than the extended-release naltrexone group (p<0.001) during the treatment period. An opioid-relapse event was defined as 10 or more days of opioid use in a 28-day period as assessed by self-report or by testing urine toxicology samples obtained every two weeks; a positive or missing sample was computed as five days of opioid use. Sixty-one percent of patients in the extended-release naltrexone group participated in all six injections during the treatment period. While the study was not powered to show statistical significance for the secondary endpoint of days of reincarceration, substantially fewer (37%) days of reincarceration were reported in the extended-release naltrexone group. Participants were followed for a total of 78 weeks. Three follow-up visits occurred during the year following the six-month treatment period, beginning at Week 27 and at six-month intervals for both arms. Opioid-use prevention effects waned after discontinuation of treatment. As noted by the authors in the study, symptoms of opioid-use disorder are more likely to recur with the discontinuation of effective pharmacotherapy as with other chronic diseases. Overall, more participants reported adverse events in the extended-release naltrexone group versus those in the usual-treatment group. The most common adverse events (≥ 10%) related to extended-release naltrexone were injection-site reaction, headache and gastrointestinal upset. Significantly fewer serious adverse events occurred with extended-release naltrexone, compared with the usual-treatment group. There were no overdose events observed in the extended-release naltrexone group in the 78-week period compared with seven overdose events, including three deaths, in the usual-treatment group. Alkermes did not have editorial control or access to trial data. The company contributed VIVITROL in kind through an investigator-initiated trial contract.