Naltrexone Abuse Indication Will Likely Require Monitoring and Support Services

Naltrexone is safe and effective for the treatment of opioid abuse, but the company should build on existing labeling that calls for monitoring and support as essential parts of therapy, a Food and Drug Administration advisory panel said.

Lingering concerns about the applicability of the results from the single clinical trial, which was conducted in Russia, to the U.S. population were not enough to stem the tide of support. On Sept. 16, the Psychopharmacologic Drugs Advisory Committee voted 11-2 with no abstentions that data from the trial were sufficient to demonstrate efficacy, 10-1 with two abstentions that the data could be applied to the U.S. population, 12-0 with one abstention that the safety data were adequate, and 12-1 that the supplemental indication should be approved.

Alkermes Inc., maker of naltrexone under the name Vivitrol, has a head start on the monitoring and support question from the drug’s current label for alcohol abuse treatment, which states: “Alcohol-dependent patients, including those taking Vivitrol, should be monitored for the development of depression or suicidal thinking. Families and caregivers of patients being treated with Vivitrol should be alerted to the need to monitor patients for the emergence of symptoms of depression or suicidality, and to report such symptoms to the patient’s health care provider.”

The label also says that “patients should be advised that Vivitrol has been shown to treat alcohol dependence only when used as part of a treatment program that includes counseling and support.”

Citing a presentation delivered on behalf of Alkermes by Dr. Paul Earley, medical director of the Talbott Recovery Campus, panel member Chung-yui Betty Tai, Ph.D., of the National Institute on Drug Abuse, said that Vivitrol “is a good medication for young [patients with a] short addiction history [who are] highly motivated, such as addicted professionals, and also with strong social and family support. Based on those, I think that’s comparable to the Russian population in the study, based on the report I have reviewed.”

“I am of the belief that no one piece of treatment decides totally what the outcome is,” Louis Baxter, executive medical director of the Professional Assistance Program of New Jersey, said. “So using this medicine in conjunction with the other elements of addiction treatment, I believe that we will actually be able to observe those same results [as in the Russian trial] and perhaps even better.”

‘It’s Rare to See Data This Robust’

Data from an intent-to-treat analysis of the 250 patients enrolled in the study showed that the 126 patients treated once monthly with Vivitrol had 90% opioid-free urine screens, compared with 35% for the 124 patients taking a placebo.

“It’s rare to see data this robust to show the efficacy, although it’s from a single trial,” Dr. Tai said, citing her long experience doing clinical trials for drug addiction treatments.

The FDA’s official view going into the meeting was almost unequivocally positive as well. “I think we’ve made it clear that we agreed with the sponsor that they have demonstrated efficacy and that there are no particularly concerning new safety signals with this formulation. And really, we did not find any concerns related to the data integrity from the one study,” Dr. Bob Rappoport, director of the division of anesthesia and analgesia products, said. However, he added, “the single study done in Russia still raises questions. ... I think we feel that we’ve adequately addressed those questions to our level of comfort, but we want to hear from [the advisory committee].”

This apparently refers to a concern raised in background materials released before the meeting that there was a lower rate of adverse events in the Russian study than in prior studies conducted in the United States, and there might be a “cultural norm” in Russia of underreporting adverse events.

However, this question was addressed in a presentation by Dr. Tejashri Purohit-Sheth, branch chief for Good Clinical Practice 2 at the FDA’s division of scientific investigations, who said that the agency found in its inspection of 4 of the 13 Russian sites that “adverse event and serious adverse event reporting [were] adequate,” and that there was “no evidence of underreporting.”

“The data is reliable in support of the application,” she said.

That didn’t mean the committee found Vivitrol to be completely free of all safety concerns, such as the risk that addicts taking the drug and finding their cravings suppressed will take more opioid to try to get high and end up overdosing. But the general sense of the committee seemed to be expressed by Dr. Michael Hwang of Robert Wood Johnson Medical School, who said, “All medications inherently carry some risks, and given the scope of the [addiction] problem here, I think it is safe.”

Naltrexone is safe and effective for the treatment of opioid abuse, but the company should build on existing labeling that calls for monitoring and support as essential parts of therapy, a Food and Drug Administration advisory panel said.

Lingering concerns about the applicability of the results from the single clinical trial, which was conducted in Russia, to the U.S. population were not enough to stem the tide of support. On Sept. 16, the Psychopharmacologic Drugs Advisory Committee voted 11-2 with no abstentions that data from the trial were sufficient to demonstrate efficacy, 10-1 with two abstentions that the data could be applied to the U.S. population, 12-0 with one abstention that the safety data were adequate, and 12-1 that the supplemental indication should be approved.

Alkermes Inc., maker of naltrexone under the name Vivitrol, has a head start on the monitoring and support question from the drug’s current label for alcohol abuse treatment, which states: “Alcohol-dependent patients, including those taking Vivitrol, should be monitored for the development of depression or suicidal thinking. Families and caregivers of patients being treated with Vivitrol should be alerted to the need to monitor patients for the emergence of symptoms of depression or suicidality, and to report such symptoms to the patient’s health care provider.”

The label also says that “patients should be advised that Vivitrol has been shown to treat alcohol dependence only when used as part of a treatment program that includes counseling and support.”

Citing a presentation delivered on behalf of Alkermes by Dr. Paul Earley, medical director of the Talbott Recovery Campus, panel member Chung-yui Betty Tai, Ph.D., of the National Institute on Drug Abuse, said that Vivitrol “is a good medication for young [patients with a] short addiction history [who are] highly motivated, such as addicted professionals, and also with strong social and family support. Based on those, I think that’s comparable to the Russian population in the study, based on the report I have reviewed.”

“I am of the belief that no one piece of treatment decides totally what the outcome is,” Louis Baxter, executive medical director of the Professional Assistance Program of New Jersey, said. “So using this medicine in conjunction with the other elements of addiction treatment, I believe that we will actually be able to observe those same results [as in the Russian trial] and perhaps even better.”

‘It’s Rare to See Data This Robust’

Data from an intent-to-treat analysis of the 250 patients enrolled in the study showed that the 126 patients treated once monthly with Vivitrol had 90% opioid-free urine screens, compared with 35% for the 124 patients taking a placebo.

“It’s rare to see data this robust to show the efficacy, although it’s from a single trial,” Dr. Tai said, citing her long experience doing clinical trials for drug addiction treatments.

The FDA’s official view going into the meeting was almost unequivocally positive as well. “I think we’ve made it clear that we agreed with the sponsor that they have demonstrated efficacy and that there are no particularly concerning new safety signals with this formulation. And really, we did not find any concerns related to the data integrity from the one study,” Dr. Bob Rappoport, director of the division of anesthesia and analgesia products, said. However, he added, “the single study done in Russia still raises questions. ... I think we feel that we’ve adequately addressed those questions to our level of comfort, but we want to hear from [the advisory committee].”

This apparently refers to a concern raised in background materials released before the meeting that there was a lower rate of adverse events in the Russian study than in prior studies conducted in the United States, and there might be a “cultural norm” in Russia of underreporting adverse events.

However, this question was addressed in a presentation by Dr. Tejashri Purohit-Sheth, branch chief for Good Clinical Practice 2 at the FDA’s division of scientific investigations, who said that the agency found in its inspection of 4 of the 13 Russian sites that “adverse event and serious adverse event reporting [were] adequate,” and that there was “no evidence of underreporting.”

“The data is reliable in support of the application,” she said.

That didn’t mean the committee found Vivitrol to be completely free of all safety concerns, such as the risk that addicts taking the drug and finding their cravings suppressed will take more opioid to try to get high and end up overdosing. But the general sense of the committee seemed to be expressed by Dr. Michael Hwang of Robert Wood Johnson Medical School, who said, “All medications inherently carry some risks, and given the scope of the [addiction] problem here, I think it is safe.”

Naltrexone is safe and effective for the treatment of opioid abuse, but the company should build on existing labeling that calls for monitoring and support as essential parts of therapy, a Food and Drug Administration advisory panel said.

Lingering concerns about the applicability of the results from the single clinical trial, which was conducted in Russia, to the U.S. population were not enough to stem the tide of support. On Sept. 16, the Psychopharmacologic Drugs Advisory Committee voted 11-2 with no abstentions that data from the trial were sufficient to demonstrate efficacy, 10-1 with two abstentions that the data could be applied to the U.S. population, 12-0 with one abstention that the safety data were adequate, and 12-1 that the supplemental indication should be approved.

Alkermes Inc., maker of naltrexone under the name Vivitrol, has a head start on the monitoring and support question from the drug’s current label for alcohol abuse treatment, which states: “Alcohol-dependent patients, including those taking Vivitrol, should be monitored for the development of depression or suicidal thinking. Families and caregivers of patients being treated with Vivitrol should be alerted to the need to monitor patients for the emergence of symptoms of depression or suicidality, and to report such symptoms to the patient’s health care provider.”

The label also says that “patients should be advised that Vivitrol has been shown to treat alcohol dependence only when used as part of a treatment program that includes counseling and support.”

Citing a presentation delivered on behalf of Alkermes by Dr. Paul Earley, medical director of the Talbott Recovery Campus, panel member Chung-yui Betty Tai, Ph.D., of the National Institute on Drug Abuse, said that Vivitrol “is a good medication for young [patients with a] short addiction history [who are] highly motivated, such as addicted professionals, and also with strong social and family support. Based on those, I think that’s comparable to the Russian population in the study, based on the report I have reviewed.”

“I am of the belief that no one piece of treatment decides totally what the outcome is,” Louis Baxter, executive medical director of the Professional Assistance Program of New Jersey, said. “So using this medicine in conjunction with the other elements of addiction treatment, I believe that we will actually be able to observe those same results [as in the Russian trial] and perhaps even better.”

‘It’s Rare to See Data This Robust’

Data from an intent-to-treat analysis of the 250 patients enrolled in the study showed that the 126 patients treated once monthly with Vivitrol had 90% opioid-free urine screens, compared with 35% for the 124 patients taking a placebo.

“It’s rare to see data this robust to show the efficacy, although it’s from a single trial,” Dr. Tai said, citing her long experience doing clinical trials for drug addiction treatments.

The FDA’s official view going into the meeting was almost unequivocally positive as well. “I think we’ve made it clear that we agreed with the sponsor that they have demonstrated efficacy and that there are no particularly concerning new safety signals with this formulation. And really, we did not find any concerns related to the data integrity from the one study,” Dr. Bob Rappoport, director of the division of anesthesia and analgesia products, said. However, he added, “the single study done in Russia still raises questions. ... I think we feel that we’ve adequately addressed those questions to our level of comfort, but we want to hear from [the advisory committee].”

This apparently refers to a concern raised in background materials released before the meeting that there was a lower rate of adverse events in the Russian study than in prior studies conducted in the United States, and there might be a “cultural norm” in Russia of underreporting adverse events.

However, this question was addressed in a presentation by Dr. Tejashri Purohit-Sheth, branch chief for Good Clinical Practice 2 at the FDA’s division of scientific investigations, who said that the agency found in its inspection of 4 of the 13 Russian sites that “adverse event and serious adverse event reporting [were] adequate,” and that there was “no evidence of underreporting.”

“The data is reliable in support of the application,” she said.

That didn’t mean the committee found Vivitrol to be completely free of all safety concerns, such as the risk that addicts taking the drug and finding their cravings suppressed will take more opioid to try to get high and end up overdosing. But the general sense of the committee seemed to be expressed by Dr. Michael Hwang of Robert Wood Johnson Medical School, who said, “All medications inherently carry some risks, and given the scope of the [addiction] problem here, I think it is safe.”