An abuse-deterrent stimulant product for attention deficit-hyperactivity disorder (ADHD) got a skeptical review from FDA technical staff ahead of an advisory committee meeting later this week.
AR19 is an oral amphetamine sulfate immediate-release capsule formulated to reduce non-oral abuse. The drug, developed by Arbor Pharmaceuticals, will go before the Psychopharmacologic Drugs Advisory Committee (PDAC) and the Drug Safety and Risk Management (DSaRM) Advisory Committee on Thursday.
The main question looming over AR19 is whether it will indeed deter intranasal and IV abuse through its novel formulation. In briefing documents prepared for panel members, FDA staff suggested they weren’t persuaded by the company’s studies.
Non-medical use of prescription stimulants has remained relatively stable since 2010 and, in 2018, 2% of the U.S. population was misusing stimulants, according to the briefing documents. Young adults are more likely than adults of other ages to misuse stimulants, and the vast majority of misuse occurs orally.
However, based on the immediate-release properties of AR19 capsules, the drug was not intended to and “will not deter abuse by the oral route,” the agency staff stated.
Intranasally, AR19 “did not provide convincing evidence” of abuse-deterred effects compared to 10-mg amphetamine sulfate in a human abuse potential (HAP) study, wrote Tiffany R. Farchione, MD, acting deputy director of the psychiatry division of the FDA Office of Neuroscience, in the briefing documents.
The drug failed to demonstrate a 10% reduction in the reinforcing properties outlined in the HAP study. However, that study was later invalidated because the drugmaker did not prespecify a protocol that removed outlier subjects, the agency staff stated.
Regardless, in a post-hoc analysis conducted by the FDA that excluded outliers, “drug liking” — a measure of abuse liability — was not significantly different between groups either.
In syringeability studies submitted in the application, it was feasible to extract at least 10 mg of amphetamine sulfate per liter when using the higher doses of AR19 (20 mg and 40 mg), which constitutes the minimum reinforcing dose, according to the briefing documents.
Although there were no safety concerns identified with the administration of AR19 when taken orally, the formulation of the drug has been linked with toxicities, such as hemolysis and thrombotic microangiopathy, when manipulated for unintended routes of administration, the agency stated.
Arbor Pharmaceuticals seeks approval and labeling of AR19 as an Abuse-Deterrent Opioid because there is no established pathway for developing abuse-deterrent stimulants.
“The patterns of misuse and abuse, morbidity, and mortality associated with prescription stimulants are different from those associated with prescription opioids, and the [FDA] has not determined that prescription stimulant products warrant the same regulatory approach as opioid analgesics with regard to [abuse-deterrent formulations],” Farchione wrote.
She noted that the FDA has also “expressed concerns” that the term “abuse deterrent” is often misinterpreted to mean a drug carries a lower risk of addiction.
AR19 contains the same active ingredient as Evekeo (amphetamine sulfate), Arbor Pharmaceuticals’ FDA-approved ADHD treatment. AR19 has been shown to reduce symptoms in adults with ADHD. The proposed dosing ranges