FDA approves Simtriyo, the first triple reuptake inhibitor for ADHD

The FDA has approved a new type of medication for patients with attention-deficit hyperactivity disorder (ADHD): Otsuka’s Simtriyo (centanafadine), which is approved for adults and children six years of age and older.

ADHD is a chronic neurodevelopmental disorder that causes impairments in attention, hyperactivity and impulsivity. In the United States, it affects approximately 7 million children and 15.5 million adults, according to the CDC.

Simtriyo is an extended-release capsule that inhibits the reuptake of three neurotransmitters: norepinephrine, dopamine and serotonin. The medication increases the availability of norepinephrine and dopamine, two neurotransmitters that are important in attention and executive function, as well as regulating serotonin, which is important for emotional regulation.

Simtriyo is expected to be available later this year. Simtriyo is under controlled substance scheduling with the U.S. Drug Enforcement Administration, and it will be available following final scheduling designation. Once regulatory requirements have been completed, additional details about the wholesale acquisition will become available, a company spokesperson told Managed Healthcare Executive.

“Because of the heterogenic nature of ADHD, many patients continue to experience symptoms that can interfere with daily functioning. The approval of Simtriyo introduces a novel mechanism of action and expands the range of options available to healthcare professionals and patients,” Lenard A. Adler, M.D., director of the adult ADHD program at NYU Langone Health, said in a news release. “Having more therapeutic choices is important because ADHD is a highly individualized condition and treatment decisions should reflect the unique needs of each patient.”

The approval was based on the results of four phase 3 clinical trials that evaluated the efficacy and safety of Simtriyo when taken by adults, adolescents, and pediatric patients.

In two trials with adults, a total of 744 patients were included in the post hoc analyses of two different doses compared with placebo. 242 adults received Simtriyo 200 mg, 241 patients received Simtriyo 400 mg and 261 patients received placebo.

In the adult trials, Simtriyo demonstrated statistically significant improvements in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total scores compared with the placebo. Improvements were observed as early as week one and maintained throughout the six-week treatment period.

The trials with adolescents and children, high-dose Simtriyo demonstrated statistically significant improvements in ADHD Rating Scale-5 (ADHD-RS-5) total scores compared with placebo. Improvements were observed as early as week one.

The most common adverse reactions were rash and decreased appetite in children 6 to 12 years of age; decreased appetite, nausea, rash, headache and abdominal pain in adolescents 13 to 17 years of age; and headache, decreased appetite, insomnia, nausea, dry mouth, and diarrhea in adults.

The prescribing information includes two boxed warnings, including about the risk of suicidal ideation and behavior in patients 6 to 12 years of age. The second warns about the risk of abuse, misuse and addiction.

Clinical research on Simtriyo continues. In a recently completed phase 3b study in adults with ADHD and comorbid anxiety, Simtriyo demonstrated statistically significant improvements in ADHD symptoms compared with placebo. Full study results will be presented at an upcoming scientific meeting. As many as half of all ADHD patients also suffer from at least one comorbid anxiety disorder, which has been associated with higher rates of suicidality and hospitalization.