CAMBRIDGE, MASS., September 9, 2010—Seaside Therapeutics, Inc. announced today positive data from an open-label Phase 2 study of STX209 conducted in patients with autism spectrum disorders (ASD). The primary endpoint of the study, an improvement on the Irritability subscale of the Aberrant Behavior Checklist (ABC-I), achieved statistical significance (p<0.001). In addition, STX209 demonstrated statistically significant improvements across a number of other global and specific neurobehavioral outcomes, including improvements on the Social Withdrawal subscale of the Aberrant Behavior Checklist (ABC-SW, p<0.001), which assesses a core symptom of ASD. A significant number of patients enrolled in the study are participating in an open-label extension study. STX209 is a selective gamma-amino butyric acid type B (GABA-B) receptor agonist being studied for the treatment of ASD and fragile X syndrome (FXS). In July 2010, Seaside reported clinically meaningful data from a randomized, placebo-controlled study of STX209 in individuals with FXS. The Company intends to present the full results from both studies at future medical meetings.
“We observed marked improvement in the majority of patients treated in the STX209 autism spectrum disorders study, including reductions in agitation and tantrums,” said Craig A. Erickson, M.D., Assistant Professor of Psychiatry, Chief of the Christian Sarkine Autism Treatment Center, Chief of the Fragile X Research Treatment Center at the Indiana University School of Medicine and an investigator in the study. “STX209 was well tolerated and most study participants continue to receive treatment in an open-label extension study. The importance of novel therapeutic development in neurodevelopmental disorders such as autism spectrum disorders and fragile X syndrome cannot be underestimated. This work will potentially open up a door to treating disorders that has, until recently, been firmly shut.”
“These study results add to a growing body of evidence supporting the potential of STX209 to play an important role in treating neurodevelopment disorders such as fragile X syndrome and autism spectrum disorders,” said Randall L. Carpenter, M.D., President and Chief Executive Officer of Seaside Therapeutics. “In addition, we have now observed significant improvement in social interaction across two studies. We believe the reduction in social withdrawal is important as it suggests that STX209 is demonstrating efficacy for a core symptom of both fragile X syndrome and autism. We look forward to initiating later stage clinical studies of STX209 in both fragile X syndrome and autism spectrum disorders.”
Per Protocol Population:
In the per protocol population of 25 patients, the primary endpoint of the study, improvement on the Irritability subscale of the Aberrant Behavior Checklist (ABC-I), was met (p<0.001). STX209 also demonstrated statistically significant improvements across a broad range of measures, including the ABC-SW subscale (p<0.001), reflecting improvement on a core symptom of both fragile X syndrome and ASD, and the ABC-Total scale (p<0.001), which evaluates a number of neurobehavioral outcomes, including hyperactivity, inappropriate speech and repetitive behavior. In addition, STX209 demonstrated statistical significance across key global measures, including investigators’ assessments of Clinical Global Impressions of Improvement (CGI-I) (p=0.001) and Severity (CGI-S) (p=0.002) and other focused measures of social responsiveness, anxiety, hyperactivity and adaptive function.
STX209 was well-tolerated and there were no metabolic side effects observed. One serious adverse event was reported, worsening of aggression, which occurred during taper of STX209 in a subject who had shown significant improvement while taking the drug. Two subjects withdrew due to adverse events, one during initial up-titration of drug and one during the treatment period, due to worsening of their baseline symptoms. The most common adverse events were agitation (22%), irritability (22%), fatigue (16%), hyperactivity (16%), diarrhea (13%) and insomnia (13%). Most events resolved spontaneously or with adjustment of drug dose.
The STX209 trial was a Phase 2 open-label study designed to explore safety and efficacy of STX209 in patients with ASD. Thirty-two patients with autism spectrum disorders were enrolled, with 28 patients completing the study. The patients ranged in age from 6-17 years. A broad range of behavioral and cognitive outcomes were included in the study design to add to the Company’s knowledge of potential efficacy measures in patients with ASD.
Key inclusion/exclusion criteria included a diagnosis of autism or a diagnosis of Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS). PDD-NOS is a condition on the autism spectrum in which individuals demonstrate multiple symptoms classically associated with autism but of a scope or severity lower than in patients who meet full criteria for autism. In addition, patients in the study had to demonstrate a minimum severity on the ABC-I scale and were not allowed antipsychotic medications. Stable dosing of other medications was required for four weeks prior to entering the study.
Dosing was conducted as a flexible titration over two weeks to the optimal titrated dose (OTD). The starting dose was 1 mg twice a day and was gradually increased up to 10 mg three times a day for subjects greater than 11 years of age. OTD was continued for the remainder of the eight-week treatment period.
STX209 is a selective gamma-amino butyric acid type B (GABA-B) receptor agonist. Many aspects of certain neurodevelopmental disorders, including fragile X syndrome (FXS) and autism spectrum disorders (ASD), are believed to be caused by excessive activation of glutamate receptors and abnormally high ratios of excitatory to inhibitory neurotransmission in the brain. GABA-B receptors play an important role in modulating the release of glutamate and maintaining the optimal excitatory-inhibitory balance. STX209 has demonstrated efficacy in animal models, suggesting that altered excitatory and inhibitory neurotransmission can be corrected by activation of GABA-B receptors, thus ameliorating functional deficits in individuals with FXS and ASD.
Autism is characterized by three hallmark behaviors that can range from mild to disabling, including difficulties with social interaction, problems with verbal and nonverbal communication and repetitive behaviors or narrow, obsessive interests. Experts estimate that as many as 1 in 100 children have an autism spectrum disorder, with boys being four times more likely than girls to be diagnosed with the disorder. There is no cure for autism. A variety of medications and behavioral interventions are used in an attempt to address individual symptoms of the disease.
About Seaside Therapeutics:
Seaside Therapeutics, Inc. is creating novel drug treatments to correct or improve the course of fragile X syndrome, autism and other neurodevelopmental disorders. The Company is dedicated to translating breakthrough discoveries in neurobiology into therapeutics that improve the lives of patients and their families. For more information please visitwww.seasidetherapeutics.com.