ADHD Drug Achieves Endpoints in Phase 3 Trial

Data from a phase 3 study on guanfacine (Intuniv, Shire and Shionogi) for the treatment of attention-deficit hyperactivity disorder (ADHD) has shown that the drug has hit its primary endpoint.

The trial is the first ever to evaluate guanfacine in adults with ADHD. The drug is already approved to treat children and adolescents aged 6 to 17 years in the United States, Japan, and Europe.

“The positive topline results of this Phase 3 study provide us with important data and insights regarding the clinical profile of INTUNIV in adult patients with ADHD,” Brigitte Robertson (pictured), MD, vice president and head of global clinical development at Shire, said in a statement. “We are evaluating the full data set, and excited to advance the development of INTUNIV as a non-stimulant treatment option for adults with ADHD in Japan, building on the established efficacy and safety data for ADHD in child and adolescent patients.”

Tested in a once-daily 4 to 6 mg dose, the prolonged release hydrochloride treatment was compared to placebo, demonstrating superiority in change from baseline total score on the ADHD-RS-IV rating scale with adult prompts.

In the 12-week study, 201 adults aged 18 years and older, with ADHD were randomized to either guanfacine or placebo. The guanfacine arm also showed a “nominal significance” over the placebo arm in the efficacy analysis of the clinical global impression improvement scale (CGI-I), which implies that more patients in the treatment group achieved “marked clinical improvement in global functioning,” according to Shire.

"I think that’s yet to be seen [how it will impact active clinicians], and as clinicians become familiar with it, we’ll have to see how they utilize it," Robertson said. "We have a ways to go. I’d imagine that the fact that it was effective and had similar safety profile will make it something clinicians are interested in."

The selective alpha-2A adrenergic receptor agonist has a fairly unique mechanism of action for treating ADHD. The results are suggestive that the drug exerts physiological effects through stimulation of the alpha-2A adrenergic receptor in the brain’s control center for attention and social behavior, the prefrontal cortex.

The presence of treatment-emergent adverse events was considered mild to moderate in severity, and in line with previous studies on the treatment. Only somnolence, dry mouth, blood pressure decrease, nasopharyngitis, dizziness postural, and constipation occurred in more than or equal to 10% of patients.

“I think that, as we’ve become aware of, the adult is an emerging market and we haven’t had as much information, so this can broaden and provide different options for patients,” Robertson told MD Magazine. “I would say that the nice thing is that it provides an alternative to stimulants, as there’s only one other alternative to available. We know that patients have individualized responses to treatments, so it’s good to have more options. It’s not one-size-fits-all.”

The World Health Organization’s (WHO) mental health surveys estimate that ADHD is prevalent in 3.4% of the adult population (1.2 %to 7.3% range). The condition is still not fully understood. According to Alexandra Khachatryan, associate director of neuroscience global ORE, at Shire Pharmaceuticals, the condition is still under-recognized.