Supernus Pharmaceuticals, Inc., a specialty pharmaceutical company, has received positive topline results from its phase IIb study on SPN-810 for the treatment of impulsive aggression in ADHD patients. A total of 121 patients were randomized in the study across placebo and three doses of SPN-810.

The study is a multi-centre randomized, double-blind, placebo controlled clinical trial in children six to 12 diagnosed with Attention Deficit and Hyperactivity Disorder (ADHD) and characterised by impulsive aggression that is not controlled by optimal stimulant and psychosocial treatment.

The primary endpoints in the study were the effect in reducing impulsive aggression as measured with change in the score of the Retrospective - Modified Overt Aggression Scale "R-MOAS", and the rate of remission of aggression, after at least three weeks of treatment. Secondary endpoints included safety and tolerability of SPN-810 as well as the effect on the Clinical Global Impression and the Swanson, Nolan and Pelham Rating Scale (SNAP-IV) for ADHD. Patients who completed the study were offered the opportunity to continue into a six months open-label phase that is currently on-going. The study is a dose finding study with the primary objective of identifying effective doses in children of different weight groups.

For all patients, low and medium doses of SPN-810 met the efficacy endpoint of rate of remission of aggression and showed statistical significance vs placebo with p-values of 0.009 and 0.043 and percent of patients with R-MOAS remission of 51.9 per cent and 40.0 per cent, respectively. The low and medium doses showed a reduction in score for the R-MOAS of 62.6 per cent and 57.9 per cent, respectively, with p-values of 0.071 and 0.115.

For patients of 30 kg or more in weight, the low and medium doses of SPN-810 showed statistical significance vs placebo on the change in R-MOAS primary endpoint with p-values of 0.024 and 0.049, and high percent reduction in the R-MOAS scores of 80.9 per cent and 75.2 per cent, respectively. In addition, both doses resulted in remission of aggression with statistical significance vs placebo with p-values of 0.004 and 0.021 with percent of patients with R-MOAS remission of 66.7 per cent and 53.3 per cent, respectively. The low dose also met the secondary endpoints of Clinical Global Impression for Severity and Improvement, and of the SNAP-IV rating for Oppositional Defiant Disorder with statistical significance vs placebo with p-values of 0.007, 0.017 and 0.039, respectively, and improvements of 41.3 per cent, 34.5 per cent and 49.3 per cent. The high dose did not show statistically significant efficacy across any of these measures.

For patients under 30 kg in weight, while the low and medium doses showed improvements over placebo in the primary endpoints and the SNAP-IV rating for Oppositional Defiant Disorder, the studied doses did not show statistical significance vs placebo on efficacy measures. Coupled with the fact that the high dose did not show efficacy with statistical significance, this unexpected result leads us to believe that the most effective doses are those that achieve certain plasma concentrations (related to body weight) that do not exceed a level beyond which some sort of saturation threshold is reached.

Supernus will be conducting further analyses of the full dataset including analyzing the pharmacokinetic (PK) and pharmacodynamic (PD) relationship from the PK data generated from the study at various doses for patients in different weight groups.

"We are very excited about the positive results exhibited by SPN-810 at lower doses. The study accomplished its objectives of establishing a dose range at which the drug is effective and confirmed the efficacy of SPN-810 (molindone hydrochloride extended release formulation) in the treatment of impulsive aggression in ADHD patients," said Jack Khattar, Supernus president and CEO. "Because we have seen clear and consistent efficacy demonstrated by the low and medium doses in this study across several measures we have decided to advance the programme into later stage development. We will be analyzing the full dataset in depth, and subsequently planning on meeting with the FDA to discuss next steps in the development program and the design and protocol for phase III clinical trials."

SPN-810 was well tolerated throughout the study across all doses. The two serious adverse events that occurred were not drug related. One patient in the low dose arm and two patients in the medium dose arm had severe adverse events that were considered either possibly or definitely related to the drug. Six patients in total discontinued the study because of adverse events in the active treatment arms: one in low dose; two in medium dose; and three in high dose. Analysis of all safety and clinical lab data has not yet been completed, though SPN-810 seemed to have a very good safety and tolerability profile with low incidence of adverse events, and no unexpected, life threatening, or limiting safety issues.

SPN-810 is a molecule that has been previously approved in the United States for treatment of other indications. It has a mechanism of action that Supernus believes is promising for the treatment of aggression and serious conduct problems. Approximately 25 per cent of children with ADHD exhibit persistent conduct problems, such as impulsive aggression.

Currently there are no products approved for treating impulsive aggression in patients with ADHD and SPN-810 represents a novel approach to addressing this unmet medical need.

Supernus Pharmaceuticals, Inc. is a specialty pharmaceutical company focused on developing and commercializing products for the treatment of central nervous system, or CNS, diseases.