Amphetamine Aspartate/Amphetamine Sulfate/Dextroamphetamine Saccharate/Dextroamphetamine Sulfate

The FDA has approved Otsuka Pharmaceutical’s once-daily extended-release capsule Simtriyo (centanafadine) for attention-deficit/hyperactivity disorder (ADHD) in patients aged 6 years and older. Approval of the first-in-class norepinephrine, dopamine, serotonin reuptake inhibitor (NDSRI) gives the Japanese drugmaker its “next major CNS launch” and positions the therapy to become a potential blockbuster in a large, under-penetrated market, according to Jefferies analysts in a July 26 note. Before Simtriyo can launch in the U.S. market, it must clear controlled-substance review by the Drug Enforcement Administration (DEA), a standard, up-to-three-month procedure for all central nervous system stimulants. How the DEA classifies Simtriyo could determine its commercial potential, the Jefferies team noted. A Schedule II designation like what Adderall and Vyvanse have could restrict uptake, while a lower classification could give Simtriyo a competitive edge in a crowded ADHD market, the analysts said. During an investor Q&A in April, Otsuka said it was not clear whether a DEA review would be necessary. The FDA classifies Simtriyo as a stimulant likely because it has dopaminergic effects, the Jefferies team observed in their Sunday note. By inhibiting the reuptake of those neurotransmitters, Simtriyo works by increasing their availability in attention and behavioral pathways. A chronic neurodevelopmental disorder characterized by trouble paying attention and controlling impulsive behaviors, ADHD affects about 7 million children in the U.S. and 15.5 million adults, according to the CDC. Stimulants are the most popular treatments for ADHD, but patients often stop or cycle through different therapies due to a lack of effectiveness, troublesome side effects and changing life demands. “We therefore view the market as capable of supporting multiple treatment classes and believe Simtriyo has an opportunity to expand the overall non-stimulant segment rather than simply take share from existing products such as Qelbree or Strattera,” the Jefferies team wrote. Based on the large market, Otsuka has targeted Simtriyo peak sales of more than 100 billion Japanese yen ($610 million). The company got the drug from its 2017 acquisition of Neurovance for $100 million upfront and up to $150 million in potential development and regulatory milestone payments. Simtriyo proved its worth in four phase 3 clinical trials. It significantly improved ADHD symptoms compared with placebo as measured by the ADHD Rating Scale-5 (ADHD-RS-5) in two pediatric trials and by the Adult ADHD Investigator Symptom Rating Scale (AISRS) in two adult studies. Across the four studies, 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. A month ago, Otsuka provided positive topline phase 3b results , showing Simtriyo also beat placebo on AISRS in patients with ADHD and comorbid anxiety. “The approval of Simtriyo introduces a novel mechanism of action and expands the range of options available to healthcare professionals and patients,” Lenard Adler, director of the adult ADHD program at NYU Langone Health and an investigator on the centanafadine studies, said in a July 24 statement. “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 green light for Simtriyo comes less than a year after the FDA refused to approve Otsuka and partner Lundbeck’s Rexulti as part of a combination for post-traumatic stress disorder due to mixed trial data. The ADHD drug expands Otsuka’s CNS portfolio beyond Rexulti and Abilify Maintena, both atypical antipsychotics approved to treat schizophrenia and other neurological disorders. “ADHD is primarily treated in the community setting, giving Otsuka access to a broad prescriber base and an opportunity to leverage its established US commercial infrastructure,” Jefferies analysts said.