The FDA approved oral centanafadine (Simtriyo), a first-in-class triple reuptake inhibitor for attention deficit-hyperactivity disorder (ADHD), Otsuka announced late last week.
The once-daily extended-release capsule — a norepinephrine, dopamine, and serotonin reuptake inhibitor that functions as a central nervous system stimulant — is indicated for patients ages 6 years and older who weigh at least 20 kg (44 lb).
“By inhibiting the reuptake of norepinephrine, dopamine, and serotonin, Simtriyo increases the availability of these neurotransmitters in pathways involved in attention and behavioral regulation,” the drugmaker explained.
The approval “introduces a novel mechanism of action and expands the range of options available to healthcare professionals and patients,” said Lenard A. Adler, MD, of NYU Langone Health in New York City, in the company’s press release.
Approval was supported by results from four randomized, double-blind, placebo-controlled phase III trials: two studies in adults and two in pediatric and adolescent populations.
Across the studies, centanafadine showed statistically significant and clinically meaningful improvements in ADHD symptoms as measured by the ADHD Rating Scale-5 in children and adolescents and the Adult ADHD Investigator Symptom Rating Scale in adults. Symptom improvements were observed as early as week 1.
The most common adverse reactions were rash and decreased appetite in children ages 6 to 12 years; decreased appetite, nausea, rash, headache, and abdominal pain in teens ages 13 to 17; and headache, decreased appetite, insomnia, nausea, dry mouth, and diarrhea in adults.
An estimated 7 million children and 15.5 million adults in the U.S. live with ADHD, according to the CDC.
“ADHD can significantly affect many aspects of daily life across school, work, and relationships,” Adler noted. “Even when on treatment, because of the heterogeneic nature of ADHD, many patients continue to experience symptoms that can interfere with daily functioning.”
The drug’s label carries boxed warnings for a risk of suicidal ideation and behaviors in pediatric patients, as well as for the potential for abuse, misuse, and addiction.
Additional warnings include risks for patients with serious cardiac disease, increased blood pressure and heart rate, adverse psychiatric reactions, hypersensitivity reactions, long-term growth suppression in children, peripheral vasculopathy, serotonin syndrome, and tics.
Centanafadine is not recommended for children under 6 years due to a higher incidence of weight loss. It is contraindicated in patients with known hypersensitivity to centanafadine, those taking or within 14 days of discontinuing a monoamine oxidase inhibitor, and patients with a history of pheochromocytoma.
Otsuka said the drug will be available later this year after drug scheduling. Centanafadine also recently showed success in a phase IIIb study of adults with ADHD and comorbid anxiety.