A phase 3b trial of Otsuka’s attention-deficit/hyperactivity disorder (ADHD) prospect has hit its primary endpoint, strengthening the drugmaker’s hand weeks before a potential U.S. launch of the therapy.
The study evaluated centanafadine in adults with ADHD and comorbid anxiety. Otsuka previously tested the first-in-class norepinephrine, dopamine and serotonin reuptake inhibitor in four phase 3 ADHD trials. But with those studies restricting the enrollment of people with generalized anxiety disorder, the phase 3 program provided limited evidence in a comorbidity that affects about one-third of people with ADHD.
Otsuka filled the evidence gap by enrolling 315 people with ADHD and comorbid anxiety in a phase 3b study. Patients took centanafadine or placebo once daily. After eight weeks, Otsuka saw improvements on the Adult Investigator Symptom Rating Scale (AISRS), meeting the study’s primary endpoint.
AISRS scores fell by 18.5 points on centanafadine, compared to a 12.6-point drop on placebo. Otsuka saw statistical separation between the scores starting Week 1. The placebo-adjusted AISRS reduction—5.87 points—is numerically larger than the results Otsuka reported in two six-week phase 3 trials. The earlier trials excluded people with anxiety that could confound results or require the use of prohibited drugs.
Otsuka’s phase 3b study assessed centanafadine’s effect on anxiety as a secondary endpoint. At Week 8, the Hamilton Anxiety Rating Scale (HAM-A) total score had fallen 12.5 points on centanafadine, versus a 10.6-point decline on placebo. The 1.92-point placebo-adjusted improvement in HAM-A was statistically significant.
The data provide evidence of how centanafadine performs in “a substantial and particularly challenging population to treat,” John Kraus, M.D., Ph.D., Otsuka’s chief medical officer, said in a statement. Running the trial expanded the evidence base supporting centanafadine’s potential use “in adults with ADHD across diverse patient presentations,” Kraus added.
Otsuka has filed for FDA approval of centanafadine for the treatment of ADHD in children, adolescents and adults. The FDA is set to decide whether to authorize the molecule in that indication by July 24. Otsuka has been building (PDF) commercial infrastructure ahead of the planned launch, identifying the target medical specialties and training its sales force.
The company is laying the foundations to launch centanafadine promptly after the potential FDA approval. However, a Drug Enforcement Administration (DEA) review could delay the launch by about three months, Otsuka told investors in late April. At the time, the company was unsure whether DEA scheduling would be needed.
