The U.S. Food and Drug Administration (FDA) approved an expanded indication for viloxazine extended-release capsules (Qelbree, Supernus Pharmaceuticals, Inc.) for the treatment of attention deficit hyperactivity disorder (ADHD) in adult patients aged 18 and older. The approval is based on positive results from a randomized, double blind, placebo-controlled Phase III study of viloxazine extended-release (ER) in adults with ADHD.
The study assessed the efficacy and safety of viloxazine ER in 374 adults with ADHD and included a 2-arm flexible dose design, in which patients were randomly assigned to receive a daily dose of viloxazine ER starting with 200 mg up to 600 mg or placebo. The total duration of treatment was 6 weeks. The primary endpoint was the change from baseline to the end of the study on the total score on the ADHD Investigator Symptom Rating Scale (AISRS), an 18-item scale corresponding to 18 symptoms. The change from baseline in the Clinical Global Impression-Severity of Illness (CGI-S) score at the end of the study was the key secondary endpoint.
A total of adult patients 267 completed the trial and 107 discontinued and the average dose at end of the study was 504 mg per day. Study results showed that treatment with viloxazine ER met the primary endpoint demonstrating statistically significant improvements in ADHD symptoms compared with placebo at week 6. The change from baseline in the AISRS Total score was statistically significantly greater in adults treated with viloxazine ER compared with adults on placebo (-15.5 point change vs -11.7 point change, respectively; p = 0.004). Additionally, the study met the key secondary efficacy endpoint with statistical significance (p = 0.0023) in the change from baseline of the CGI-S Scale at week 6. Overall, viloxazine ER exhibited a good safety and tolerability profile, and the most common (≥5) treatment-related adverse events (AEs) included insomnia, headache, somnolence, fatigue, nausea, decreased appetite, dry mouth, and constipation.
The recommended starting viloxazine ER dosage for adults is 200 mg orally once daily. Dosage may be titrated in increments of 200 mg weekly to the maximum recommended dosage of 600 mg once daily, depending on response and tolerability. Viloxazine ER is currently marketed under the trade name Qelbree and is supplied as extended-release capsules containing 100mg, 150mg, or 200mg of viloxazine. Qelbree was previously approved by the FDA in April, 2021 for the treatment of ADHD in pediatric patients 6 to 17 years of age. This expanded indication makes viloxazine extended-release capsules an ADHD treatment option available for children (starting at age 6), adolescents, and adults.
>> Supernus Pharmaceuticals, Inc. Press Release
Viloxazine (figure 1) is considered a “multimodal agent” in that it both blocks the norepinephrine (NE) reuptake pump and directly modulates several serotonin (5-HT) receptors with elevation of intrasynaptic serotonin levels. Clinical data of the mechanism of action shows that in vitro, viloxazine demonstrates antagonistic activity at 5-HT2B and agonistic activity at 5-HT2C receptors, along with high receptor occupancy at clinical doses.
In vivo, viloxazine increased extracellular NE, 5-HT, and dopamine (DA) levels in the prefrontal
cortex and it produced a minimal increase in DA levels in the nucleus accumbens. Viloxazine exhibited moderate inhibitory effects on the norepinephrine transporter in vitro and in vivo and no inhibitory effect on the serotonin transporter.