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PHILADELPHIA –
The mean Abnormal Involuntary Movement Scale (AIMS) score in the study continued to increase over 3 years of treatment with this VMAT2 inhibitor, which was safe and well tolerated over the course of the study, said investigator Robert A. Hauser, MD, MBA, director of the Parkinson’s and Movement Disorder Center and professor in the department of neurology at the University of South Florida in Tampa.
The apparent improvement over time was “fascinating” to observe, Dr. Hauser said. The finding deserves further study to identify potential confounders, such as rater bias over time or placebo effects, and if those “trivial” causes can be ruled out to determine a potential mechanism of action.
“I will also say that the mechanism may not be that important if we can really show this important clinical effect,” he said. “So I think this needs more work.”
The FDA approved deutetrabenazine (Austedo, Teva) for tardive dyskinesia treatment based on ARM-TD and AIM-TD, two randomized, double-blind, placebo-controlled trials. Those studies demonstrated improvements in AIMS scores for the VMAT2 inhibitor versus placebo, with low rates of adverse events and discontinuations, Dr. Hauser said.
Dr. Hauser presented results up to week 145 from C-20, an ongoing, 3-year, open-label extension study designed to evaluate the agent’s long-term safety and efficacy.
A total of 343 patients from ARM-TD and AIM-TD rolled over directly into C-20, started at 12 mg/day of deutetrabenazine, and titrated until adequate tardive dyskinesia control was achieved, up to 48 mg/day. Sixty percent of the patients had psychotic disorders as the background comorbid illness, while 40% had mood disorders, according to the interim report.
The mean AIMS score was 10.9 at baseline, 6.0 at 54 weeks, 5.8 at 106 weeks, and 4.1 at 145 weeks, the report showed. The corresponding change in AIMS score decreased from baseline for patients who remained in the study, from –4.8 at 54 weeks to –5.6 at 106 weeks and –7.0 at 145 weeks.*
A subsequent completer analysis showed that the apparent improvement in efficacy over the long term was not due to poor responders dropping out over time, Dr. Hauser said.
“I think the data clearly show the benefit is maintained, and intriguingly, I think they suggest that there may be increasing benefit over time,” he added.
The treatment was safe and well tolerated in long-term use. The most common adverse events were anxiety, somnolence, fatigue, insomnia, and headache. Adverse events did not increase in frequency from the parent studies to the open-label study, he noted.
The study was sponsored by Teva Pharmaceuticals. Dr. Hauser reported disclosures related to Teva, AbbVie, AstraZeneca, Biotie Thrapies, Cynapsus Therapeutics, Neurocrine Biosciences, Sunovion Pharmaceuticals, and Pfizer, among others.
SOURCE: Hauser RA et al. AAN 2019. Abstract S4.009.
*Correction, 6/26/19 An earlier version of this article mischaracterized changes in the mean Abnormal Involuntary Movement Scale scores during treatment.
PHILADELPHIA –
The mean Abnormal Involuntary Movement Scale (AIMS) score in the study continued to increase over 3 years of treatment with this VMAT2 inhibitor, which was safe and well tolerated over the course of the study, said investigator Robert A. Hauser, MD, MBA, director of the Parkinson’s and Movement Disorder Center and professor in the department of neurology at the University of South Florida in Tampa.
The apparent improvement over time was “fascinating” to observe, Dr. Hauser said. The finding deserves further study to identify potential confounders, such as rater bias over time or placebo effects, and if those “trivial” causes can be ruled out to determine a potential mechanism of action.
“I will also say that the mechanism may not be that important if we can really show this important clinical effect,” he said. “So I think this needs more work.”
The FDA approved deutetrabenazine (Austedo, Teva) for tardive dyskinesia treatment based on ARM-TD and AIM-TD, two randomized, double-blind, placebo-controlled trials. Those studies demonstrated improvements in AIMS scores for the VMAT2 inhibitor versus placebo, with low rates of adverse events and discontinuations, Dr. Hauser said.
Dr. Hauser presented results up to week 145 from C-20, an ongoing, 3-year, open-label extension study designed to evaluate the agent’s long-term safety and efficacy.
A total of 343 patients from ARM-TD and AIM-TD rolled over directly into C-20, started at 12 mg/day of deutetrabenazine, and titrated until adequate tardive dyskinesia control was achieved, up to 48 mg/day. Sixty percent of the patients had psychotic disorders as the background comorbid illness, while 40% had mood disorders, according to the interim report.
The mean AIMS score was 10.9 at baseline, 6.0 at 54 weeks, 5.8 at 106 weeks, and 4.1 at 145 weeks, the report showed. The corresponding change in AIMS score decreased from baseline for patients who remained in the study, from –4.8 at 54 weeks to –5.6 at 106 weeks and –7.0 at 145 weeks.*
A subsequent completer analysis showed that the apparent improvement in efficacy over the long term was not due to poor responders dropping out over time, Dr. Hauser said.
“I think the data clearly show the benefit is maintained, and intriguingly, I think they suggest that there may be increasing benefit over time,” he added.
The treatment was safe and well tolerated in long-term use. The most common adverse events were anxiety, somnolence, fatigue, insomnia, and headache. Adverse events did not increase in frequency from the parent studies to the open-label study, he noted.
The study was sponsored by Teva Pharmaceuticals. Dr. Hauser reported disclosures related to Teva, AbbVie, AstraZeneca, Biotie Thrapies, Cynapsus Therapeutics, Neurocrine Biosciences, Sunovion Pharmaceuticals, and Pfizer, among others.
SOURCE: Hauser RA et al. AAN 2019. Abstract S4.009.
*Correction, 6/26/19 An earlier version of this article mischaracterized changes in the mean Abnormal Involuntary Movement Scale scores during treatment.
PHILADELPHIA –
The mean Abnormal Involuntary Movement Scale (AIMS) score in the study continued to increase over 3 years of treatment with this VMAT2 inhibitor, which was safe and well tolerated over the course of the study, said investigator Robert A. Hauser, MD, MBA, director of the Parkinson’s and Movement Disorder Center and professor in the department of neurology at the University of South Florida in Tampa.
The apparent improvement over time was “fascinating” to observe, Dr. Hauser said. The finding deserves further study to identify potential confounders, such as rater bias over time or placebo effects, and if those “trivial” causes can be ruled out to determine a potential mechanism of action.
“I will also say that the mechanism may not be that important if we can really show this important clinical effect,” he said. “So I think this needs more work.”
The FDA approved deutetrabenazine (Austedo, Teva) for tardive dyskinesia treatment based on ARM-TD and AIM-TD, two randomized, double-blind, placebo-controlled trials. Those studies demonstrated improvements in AIMS scores for the VMAT2 inhibitor versus placebo, with low rates of adverse events and discontinuations, Dr. Hauser said.
Dr. Hauser presented results up to week 145 from C-20, an ongoing, 3-year, open-label extension study designed to evaluate the agent’s long-term safety and efficacy.
A total of 343 patients from ARM-TD and AIM-TD rolled over directly into C-20, started at 12 mg/day of deutetrabenazine, and titrated until adequate tardive dyskinesia control was achieved, up to 48 mg/day. Sixty percent of the patients had psychotic disorders as the background comorbid illness, while 40% had mood disorders, according to the interim report.
The mean AIMS score was 10.9 at baseline, 6.0 at 54 weeks, 5.8 at 106 weeks, and 4.1 at 145 weeks, the report showed. The corresponding change in AIMS score decreased from baseline for patients who remained in the study, from –4.8 at 54 weeks to –5.6 at 106 weeks and –7.0 at 145 weeks.*
A subsequent completer analysis showed that the apparent improvement in efficacy over the long term was not due to poor responders dropping out over time, Dr. Hauser said.
“I think the data clearly show the benefit is maintained, and intriguingly, I think they suggest that there may be increasing benefit over time,” he added.
The treatment was safe and well tolerated in long-term use. The most common adverse events were anxiety, somnolence, fatigue, insomnia, and headache. Adverse events did not increase in frequency from the parent studies to the open-label study, he noted.
The study was sponsored by Teva Pharmaceuticals. Dr. Hauser reported disclosures related to Teva, AbbVie, AstraZeneca, Biotie Thrapies, Cynapsus Therapeutics, Neurocrine Biosciences, Sunovion Pharmaceuticals, and Pfizer, among others.
SOURCE: Hauser RA et al. AAN 2019. Abstract S4.009.
*Correction, 6/26/19 An earlier version of this article mischaracterized changes in the mean Abnormal Involuntary Movement Scale scores during treatment.
REPORTING FROM AAN 2019
Key clinical point: The benefit of deutetrabenazine in patients with tardive dyskinesia is maintained in the long term and may actually increase over time, though further study is needed.
Major finding: Change from baseline in Abnormal Involuntary Movement Scale (AIMS) score decreased from –4.8 at 54 weeks to –5.6 at 106 weeks and –7.0 at 154 weeks.
Study details: Interim analysis of C-20, an open-label extension study including 343 patients initially enrolled in one of two pivotal randomized phase 3 studies.
Disclosures: The study was sponsored by Teva Pharmaceuticals. Dr. Hauser reported disclosures related to Teva, AbbVie, AstraZeneca, Biotie Thrapies, Cynapsus Therapeutics, Neurocrine Biosciences, Sunovion Pharmaceuticals, and Pfizer, among others.
Source: Hauser RA et al. AAN 2019. Abstract S4.009.