Neurovance, Inc. has announced that its Phase 2b trial of centanafadine SR (CTN), a non-stimulant for the treatment of adults with ADHD, met both the primary and secondary endpoints. The trial showed that CTN at 400 mg demonstrated an effect size of 0.6, within the range of the pivotal trials of approved stimulants, the most frequently prescribed drugs in the US for ADHD. The 400 mg dose was generally well tolerated with rates of insomnia and loss of appetite less than typically seen with stimulants. This trial lays the groundwork for future phase 3 trials.
"We believe that CTN is among the first of a new generation of triple reuptake inhibitors in advanced development for ADHD and these study results are critical to establishing the dose range and regulatory path forward for centanafadine", said Anthony A. McKinney, Co-Founder, President and CEO of Neurovance. "Based on previous data we have shown, CTN had an efficacy profile approaching that of stimulants yet with human trial results suggesting less risk of abuse. We will use the data from this trial to support an FDA regulatory package with the goal of initiating phase 3 trials in early 2017."
Specifically, this was a 3-week placebo-controlled crossover Phase 2b trial in 85 adult ADHD patients conducted at 4 US sites and designed to provide efficacy and safety data for CTN given twice daily. Patients receiving CTN 400 mg had a -15.1 point change from baseline in the primary endpoint vs. a -8.1 point change observed with placebo, resulting in a statistically significant difference of -7.0 (p<0.001) and an effect size of 0.6. Effect size is a well-accepted statistical method to enable comparisons with medications across trials. Stimulants generally have effect sizes higher than non-stimulants.
"The results of CTN potentially presents a medicine with effect size and late-day symptom coverage with a low rate of insomnia - a chronic side effect of many ADHD treatments," said Timothy Wilens, MD, an ADHD researcher from Massachusetts General Hospital. "If these data are replicated in future Phase 3 trials, CTN may present a new path to further the way ADHD is treated in both adult and pediatric patients."
The results of this Phase 2b efficacy trial followed the results of a human imaging study presented recently at the ASCP national meeting in Scottsdale, Arizona, showing CTN had relevant brain norepinephrine, dopamine and serotonin transporter occupancy versus standard comparators. The imaging results are consistent with the strong efficacy signal observed in the completed ADHD trials.
"Based on my knowledge of this market from my ADHD experience at Johnson and Johnson, I was very impressed with the CTN SR results," said, Jeff Bailey, Executive Chairman of Neurovance. "If approved, CTN has the potential to be the go-to drug for payers and doctors when patients do not respond well to first-line stimulants."
CTN modulates the activity of norepinephrine (NE), dopamine (DA) and serotonin (5-HT), three neurotransmitters believed to be involved in the disorder. A total of 7 human trials have been conducted with centanafadine, five Phase 1 studies and two Phase 2 ADHD trials.
ADHD is unique among the mature US pharmaceutical markets with $12 billion in annual sales with overall prescriptions growing at 6%, which demonstrates the strong underlying demand for ADHD treatments. According to IMS, in 2015 approximately 67 million prescriptions were written for ADHD with 37 million prescriptions written for adults and 30 million written for children and adolescents. Adults are the fastest growing segment with prescriptions growing at an estimated rate of 9% per year. Over 90% of ADHD prescriptions are for stimulants such as amphetamines (mixed amphetamine salts, d-amphetamine or lisdexamfetamine) or methylphenidates, which, though effective, can have major side effects and potential for abuse and diversion.