Shionogi Inc, the US-based group company of Shionogi & Co, Ltd, announced the US Food and Drug Administration approval of the non-stimulant medication KAPVAY (clonidine hydrochloride) extended-release tablets, an extended-release oral formulation for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children and adolescents ages six-17 years.

KAPVAY is the only formulation of clonidine hydrochloride approved by the FDA for the treatment of ADHD, and is the first and only FDA-approved ADHD treatment indicated for use as add-on therapy to stimulant medication. KAPVAY can also be used as monotherapy when treating ADHD.

An oral, non-stimulant, twice-daily therapy, KAPVAY is a centrally acting alpha2-adrenergic receptor agonist. While the mechanism of action of alpha2 agonists in ADHD is not known, it is believed to involve the pre-frontal cortex (PFC) of the brain. Studies suggest that the PFC regulates attention and plays a critical role in impulse control, working memory and executive function.

“The FDA approval of KAPVAY represents an exciting milestone in the field of ADHD,” said Donald C Manning, chief medical officer of Shionogi Inc. “The extended-release formulation of KAPVAY minimizes the peaks and troughs in blood levels, thereby decreasing overactivation of the alpha receptors in the brain and periphery. We look forward to providing this important, beneficial treatment for ADHD to patients, both as monotherapy and add-on therapy to stimulants.”

“ADHD is a complex disorder that requires individualized treatment. While there are prescription treatment options available, many ADHD patients on stimulants do not achieve adequate control of symptoms,” explained Rakesh Jain, MD, MPH, director of Psychiatric Drug Research for R/D Clinical Research at Lake Jackson, Texas, and an investigator in the clinical trials. “KAPVAY™, when added to a stimulant, addresses an unmet need, and improves ADHD symptoms beyond what is achieved by stimulants alone. This is a significant step forward for the treatment of ADHD to have an approved product for add-on therapy in our treatment armamentarium.”

ADHD is a neurobehavioral disorder that occurs in childhood and may continue into adolescence and adulthood, which affects more than 4.5 million children ages 3-17 in the US. Alone. Approximately three to seven percent of US school-aged children are believed to suffer from this disorder. Symptoms include difficulty staying focused and paying attention, difficulty controlling behavior, and hyperactivity/overactivity.

This approval is based on two phase-III studies, which demonstrated efficacy at five-weeks that children and adolescents (six to 17 years) with ADHD treated with KAPVAY experienced statistically significant improvements in core symptoms of ADHD – inattention, hyperactivity and impulsivity. The most common and drug related adverse reactions (incident at least 5% and twice the rate of placebo) included somnolence, fatigue, upper respiratory tract infection (cough, rhinitis, sneezing), irritability throat pain (sore throat), insomnia, nightmares, emotional disorder, constipation, nasal congestion, increased body temperature, drug mouth and ear pain. Maintenance efficacy has not been systemically evaluated and patients who are continued on longer-term treatment require periodic reassessment.

Administered orally, clonidine hydrochloride exerts its pharmacological effects as a centrally acting alpha2-adrenoceptor agonist. The formulation in KAPVAY is designed to delay the absorption of active drug in order to decrease peak to trough plasma concentration differences.

Shionogi is a major research-driven pharmaceutical company dedicated to placing the highest value on patients. Shionogi’s Research and Development currently targets three therapeutic areas: Infectious Diseases, Pain, and Metabolic Syndrome.