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The experimental nonstimulant medication viloxazine extended-release, known as SPN-812, reduced symptoms of attention-deficit/hyperactivity disorder (ADHD) as soon as 1 week after dosing and was well tolerated in a randomized, placebo-controlled phase 3 study that included more than 400 children.
In addition to its fast onset of action, the fact that it was effective for both inattentive and hyperactive/impulsive clusters of symptoms is “impressive,” study investigator Andrew Cutler, MD, clinical professor of psychiatry, SUNY Upstate Medical University, Syracuse, N.Y., said in an interviews.
Also noteworthy was the improvement in measures of quality of life and function, “especially function in the areas of school, home life, family relations, and peer relationships, which can be really disrupted with ADHD,” Dr. Cutler said.
The findings were published online July 25 in Clinical Therapeutics.
Novel modulating agent
Viloxazine extended-release is a novel multimodal serotonergic and noradrenergic modulating agent with activity at serotonin receptors and the norepinephrine transporter.
About two-thirds were boys.
All participants had an ADHD-Rating Scale–5 (ADHD-RS-5) score of at least 28 and a Clinical Global Impression–Severity score of at least 4. None had taken ADHD medication for at least 1 week prior to randomization.
The intent-to-treat population included 460 children. Of these, 155 were randomly assigned to receive placebo, 147 to receive viloxazine 100 mg, and 158 to receive viloxazine 200 mg.
The primary efficacy endpoint was change from baseline in ADHD-RS-5 total score at week 6. Score changes for both the 100-mg (P = .0004) and the 200-mg (P < .0001) viloxazine groups met statistical significance compared with the placebo group.
Change from baseline in both the ADHD-RS-5 inattention and hyperactivity/impulsivity subscale scores was also significantly reduced in the 100-mg (P = .0006 and .0026, respectively) and 200-mg (P < .0001 and P < .0001, respectively) treatment groups compared with the placebo group.
Improvements occurred after 1 week of treatment and were maintained throughout the 6-week trial, “indicating an early and sustained effect,” the investigators wrote.
FDA target action date
The Clinical Global Impression–Improvement (CGI-I) score at 6 weeks was significantly improved in those receiving 100 mg (P = .0020) and 200 mg (P < .0001) of the active treatment compared with placebo.
The CGI-I responder rate, the percentage of children with a CGI-I score of 1 (very much improved) or 2 (much improved), was significantly higher at 6 weeks with viloxazine 100 mg and 200 mg vs. placebo (45% and 51% vs. 30%, respectively; P = .0065 and P = .0002).
These standard investigator-rated assessments were supported by two parent self-rated assessments: the Conners 3–Parent Short Form and the Weiss Functional Impairment Rating Scale–Parent Form.
Parents noted improvement not only in their children’s ADHD symptoms but also in ADHD-associated learning problems, executive functioning, defiance/aggression, peer relations, and functioning in different settings.
At both doses, once-daily viloxazine was generally well tolerated, with a low rate of discontinuation because of adverse events (<5%). Most adverse events were characterized as mild or moderate in severity and included somnolence (8.9%), decreased appetite (6.0%), and headache (5.4%).
On the basis of results of this study and others, the Food and Drug Administration accepted the company’s new drug application for viloxazine extended-release for ADHD in children and adolescents. The application has a target action date of Nov. 8, 2020.
Potential advantages
Commenting on the study in an interview, Dean Elbe, PharmD, clinical pharmacy specialist, child and adolescent mental health, BC Children’s Hospital, Vancouver, B.C., said that use of viloxazine to treat ADHD is “interesting.”
Dr. Elbe, who was not involved with the current research, noted that “it is actually an old drug that has been around since the mid-1970s in Europe as an antidepressant. It was removed from the market due to poor sales, not safety issues.”
Overall, on the basis of this study, viloxazine has potential to offer “modest improvements” over atomoxetine (Strattera), and the dosing may be “more straightforward and somewhat less challenging than with atomoxetine, with no taper up and no adjustment for poor 2D6 metabolizers,” Dr. Elbe noted.
“The onset of action appears somewhat quicker than we typically see with atomoxetine, so that is also helpful for parent and clinician acceptance and partially overcomes a perceived barrier with atomoxetine,” he said.
Dr. Elbe said he wonders, however, whether viloxazine will show “real-world clinical utility for both hyperactive-impulsive as well as inattentive symptoms. Although the study shows efficacy in both symptom clusters, so did the atomoxetine RCTs, and this has not been the clinical impression for atomoxetine.”
The study was funded by Supernus Pharmaceuticals. Dr. Cutler is a consultant for Supernus, as well as for Adlon Therapeutics, Aevi Genomics, Akili Interactive, Arbor Pharmaceuticals, Ironshore, KemPharm, Lundbeck, Neos Therapeutics, NLS Pharma, Otsuka, Purdue, Shire, Sunovion, Takeda, and Tris Pharma. He has received speaker/promotional honoraria from Adlon Therapeutics, Arbor Pharmaceuticals, Lundbeck, Neos Therapeutics, Otsuka, Shire, Sunovion, Takeda, and Tris Pharma and has received research grants from Aevi Genomics, Akili Interactive, Arbor Pharmaceuticals, Ironshore, KemPharm, Lundbeck, Neos Therapeutics, Otsuka, Purdue, Shire, Sunovion, Supernus Pharmaceuticals, Takeda, and Tris Pharma. A complete list of disclosures for the other authors is available in the original article. Dr. Elbe has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The experimental nonstimulant medication viloxazine extended-release, known as SPN-812, reduced symptoms of attention-deficit/hyperactivity disorder (ADHD) as soon as 1 week after dosing and was well tolerated in a randomized, placebo-controlled phase 3 study that included more than 400 children.
In addition to its fast onset of action, the fact that it was effective for both inattentive and hyperactive/impulsive clusters of symptoms is “impressive,” study investigator Andrew Cutler, MD, clinical professor of psychiatry, SUNY Upstate Medical University, Syracuse, N.Y., said in an interviews.
Also noteworthy was the improvement in measures of quality of life and function, “especially function in the areas of school, home life, family relations, and peer relationships, which can be really disrupted with ADHD,” Dr. Cutler said.
The findings were published online July 25 in Clinical Therapeutics.
Novel modulating agent
Viloxazine extended-release is a novel multimodal serotonergic and noradrenergic modulating agent with activity at serotonin receptors and the norepinephrine transporter.
About two-thirds were boys.
All participants had an ADHD-Rating Scale–5 (ADHD-RS-5) score of at least 28 and a Clinical Global Impression–Severity score of at least 4. None had taken ADHD medication for at least 1 week prior to randomization.
The intent-to-treat population included 460 children. Of these, 155 were randomly assigned to receive placebo, 147 to receive viloxazine 100 mg, and 158 to receive viloxazine 200 mg.
The primary efficacy endpoint was change from baseline in ADHD-RS-5 total score at week 6. Score changes for both the 100-mg (P = .0004) and the 200-mg (P < .0001) viloxazine groups met statistical significance compared with the placebo group.
Change from baseline in both the ADHD-RS-5 inattention and hyperactivity/impulsivity subscale scores was also significantly reduced in the 100-mg (P = .0006 and .0026, respectively) and 200-mg (P < .0001 and P < .0001, respectively) treatment groups compared with the placebo group.
Improvements occurred after 1 week of treatment and were maintained throughout the 6-week trial, “indicating an early and sustained effect,” the investigators wrote.
FDA target action date
The Clinical Global Impression–Improvement (CGI-I) score at 6 weeks was significantly improved in those receiving 100 mg (P = .0020) and 200 mg (P < .0001) of the active treatment compared with placebo.
The CGI-I responder rate, the percentage of children with a CGI-I score of 1 (very much improved) or 2 (much improved), was significantly higher at 6 weeks with viloxazine 100 mg and 200 mg vs. placebo (45% and 51% vs. 30%, respectively; P = .0065 and P = .0002).
These standard investigator-rated assessments were supported by two parent self-rated assessments: the Conners 3–Parent Short Form and the Weiss Functional Impairment Rating Scale–Parent Form.
Parents noted improvement not only in their children’s ADHD symptoms but also in ADHD-associated learning problems, executive functioning, defiance/aggression, peer relations, and functioning in different settings.
At both doses, once-daily viloxazine was generally well tolerated, with a low rate of discontinuation because of adverse events (<5%). Most adverse events were characterized as mild or moderate in severity and included somnolence (8.9%), decreased appetite (6.0%), and headache (5.4%).
On the basis of results of this study and others, the Food and Drug Administration accepted the company’s new drug application for viloxazine extended-release for ADHD in children and adolescents. The application has a target action date of Nov. 8, 2020.
Potential advantages
Commenting on the study in an interview, Dean Elbe, PharmD, clinical pharmacy specialist, child and adolescent mental health, BC Children’s Hospital, Vancouver, B.C., said that use of viloxazine to treat ADHD is “interesting.”
Dr. Elbe, who was not involved with the current research, noted that “it is actually an old drug that has been around since the mid-1970s in Europe as an antidepressant. It was removed from the market due to poor sales, not safety issues.”
Overall, on the basis of this study, viloxazine has potential to offer “modest improvements” over atomoxetine (Strattera), and the dosing may be “more straightforward and somewhat less challenging than with atomoxetine, with no taper up and no adjustment for poor 2D6 metabolizers,” Dr. Elbe noted.
“The onset of action appears somewhat quicker than we typically see with atomoxetine, so that is also helpful for parent and clinician acceptance and partially overcomes a perceived barrier with atomoxetine,” he said.
Dr. Elbe said he wonders, however, whether viloxazine will show “real-world clinical utility for both hyperactive-impulsive as well as inattentive symptoms. Although the study shows efficacy in both symptom clusters, so did the atomoxetine RCTs, and this has not been the clinical impression for atomoxetine.”
The study was funded by Supernus Pharmaceuticals. Dr. Cutler is a consultant for Supernus, as well as for Adlon Therapeutics, Aevi Genomics, Akili Interactive, Arbor Pharmaceuticals, Ironshore, KemPharm, Lundbeck, Neos Therapeutics, NLS Pharma, Otsuka, Purdue, Shire, Sunovion, Takeda, and Tris Pharma. He has received speaker/promotional honoraria from Adlon Therapeutics, Arbor Pharmaceuticals, Lundbeck, Neos Therapeutics, Otsuka, Shire, Sunovion, Takeda, and Tris Pharma and has received research grants from Aevi Genomics, Akili Interactive, Arbor Pharmaceuticals, Ironshore, KemPharm, Lundbeck, Neos Therapeutics, Otsuka, Purdue, Shire, Sunovion, Supernus Pharmaceuticals, Takeda, and Tris Pharma. A complete list of disclosures for the other authors is available in the original article. Dr. Elbe has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The experimental nonstimulant medication viloxazine extended-release, known as SPN-812, reduced symptoms of attention-deficit/hyperactivity disorder (ADHD) as soon as 1 week after dosing and was well tolerated in a randomized, placebo-controlled phase 3 study that included more than 400 children.
In addition to its fast onset of action, the fact that it was effective for both inattentive and hyperactive/impulsive clusters of symptoms is “impressive,” study investigator Andrew Cutler, MD, clinical professor of psychiatry, SUNY Upstate Medical University, Syracuse, N.Y., said in an interviews.
Also noteworthy was the improvement in measures of quality of life and function, “especially function in the areas of school, home life, family relations, and peer relationships, which can be really disrupted with ADHD,” Dr. Cutler said.
The findings were published online July 25 in Clinical Therapeutics.
Novel modulating agent
Viloxazine extended-release is a novel multimodal serotonergic and noradrenergic modulating agent with activity at serotonin receptors and the norepinephrine transporter.
About two-thirds were boys.
All participants had an ADHD-Rating Scale–5 (ADHD-RS-5) score of at least 28 and a Clinical Global Impression–Severity score of at least 4. None had taken ADHD medication for at least 1 week prior to randomization.
The intent-to-treat population included 460 children. Of these, 155 were randomly assigned to receive placebo, 147 to receive viloxazine 100 mg, and 158 to receive viloxazine 200 mg.
The primary efficacy endpoint was change from baseline in ADHD-RS-5 total score at week 6. Score changes for both the 100-mg (P = .0004) and the 200-mg (P < .0001) viloxazine groups met statistical significance compared with the placebo group.
Change from baseline in both the ADHD-RS-5 inattention and hyperactivity/impulsivity subscale scores was also significantly reduced in the 100-mg (P = .0006 and .0026, respectively) and 200-mg (P < .0001 and P < .0001, respectively) treatment groups compared with the placebo group.
Improvements occurred after 1 week of treatment and were maintained throughout the 6-week trial, “indicating an early and sustained effect,” the investigators wrote.
FDA target action date
The Clinical Global Impression–Improvement (CGI-I) score at 6 weeks was significantly improved in those receiving 100 mg (P = .0020) and 200 mg (P < .0001) of the active treatment compared with placebo.
The CGI-I responder rate, the percentage of children with a CGI-I score of 1 (very much improved) or 2 (much improved), was significantly higher at 6 weeks with viloxazine 100 mg and 200 mg vs. placebo (45% and 51% vs. 30%, respectively; P = .0065 and P = .0002).
These standard investigator-rated assessments were supported by two parent self-rated assessments: the Conners 3–Parent Short Form and the Weiss Functional Impairment Rating Scale–Parent Form.
Parents noted improvement not only in their children’s ADHD symptoms but also in ADHD-associated learning problems, executive functioning, defiance/aggression, peer relations, and functioning in different settings.
At both doses, once-daily viloxazine was generally well tolerated, with a low rate of discontinuation because of adverse events (<5%). Most adverse events were characterized as mild or moderate in severity and included somnolence (8.9%), decreased appetite (6.0%), and headache (5.4%).
On the basis of results of this study and others, the Food and Drug Administration accepted the company’s new drug application for viloxazine extended-release for ADHD in children and adolescents. The application has a target action date of Nov. 8, 2020.
Potential advantages
Commenting on the study in an interview, Dean Elbe, PharmD, clinical pharmacy specialist, child and adolescent mental health, BC Children’s Hospital, Vancouver, B.C., said that use of viloxazine to treat ADHD is “interesting.”
Dr. Elbe, who was not involved with the current research, noted that “it is actually an old drug that has been around since the mid-1970s in Europe as an antidepressant. It was removed from the market due to poor sales, not safety issues.”
Overall, on the basis of this study, viloxazine has potential to offer “modest improvements” over atomoxetine (Strattera), and the dosing may be “more straightforward and somewhat less challenging than with atomoxetine, with no taper up and no adjustment for poor 2D6 metabolizers,” Dr. Elbe noted.
“The onset of action appears somewhat quicker than we typically see with atomoxetine, so that is also helpful for parent and clinician acceptance and partially overcomes a perceived barrier with atomoxetine,” he said.
Dr. Elbe said he wonders, however, whether viloxazine will show “real-world clinical utility for both hyperactive-impulsive as well as inattentive symptoms. Although the study shows efficacy in both symptom clusters, so did the atomoxetine RCTs, and this has not been the clinical impression for atomoxetine.”
The study was funded by Supernus Pharmaceuticals. Dr. Cutler is a consultant for Supernus, as well as for Adlon Therapeutics, Aevi Genomics, Akili Interactive, Arbor Pharmaceuticals, Ironshore, KemPharm, Lundbeck, Neos Therapeutics, NLS Pharma, Otsuka, Purdue, Shire, Sunovion, Takeda, and Tris Pharma. He has received speaker/promotional honoraria from Adlon Therapeutics, Arbor Pharmaceuticals, Lundbeck, Neos Therapeutics, Otsuka, Shire, Sunovion, Takeda, and Tris Pharma and has received research grants from Aevi Genomics, Akili Interactive, Arbor Pharmaceuticals, Ironshore, KemPharm, Lundbeck, Neos Therapeutics, Otsuka, Purdue, Shire, Sunovion, Supernus Pharmaceuticals, Takeda, and Tris Pharma. A complete list of disclosures for the other authors is available in the original article. Dr. Elbe has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.