Seizure Disorders (Pediatric)
May 2, 2016
Novartis released results from a phase III study of Afinitor (everolimus) for reduced treatment-resistant seizures associated with tuberous sclerosis complex (TSC). The three-arm, randomized, double-blind, placebo-controlled study enrolled male and female participants (ages 2.2 to 56.3). In the study, 366 patients with TSC and treatment-resistant seizures were randomized to receive targeted concentrations of everolimus titrated to Low Exposure (LE; 3-7 ng/mL; n=117) or High Exposure (HE, 9-15 ng/mL; n =130), or placebo (n=119). The percentage reduction from baseline in seizure frequency was significantly greater among patients randomized to everolimus LE (29.3%, p=0.003; confidence interval [CI]=95%) and HE (39.6%, p<0.001; CI=95%) v. placebo (14.9%; CI=95%). Seizure response rate (50% reduction) was also significantly greater with everolimus LE (28.2%, p=0.008; CI=95%) and HE (40.0%, p<0.001; CI=95%) v. placebo (15.1%; CI=95%). The most common (20%) adverse events (AEs) reported with everolimus LE/HE v. placebo included stomatitis (28.2%/30.8% v. 3.4%), mouth ulceration (23.9%/21.5% v. 4.2%), and diarrhea (17.1%/21.5% v. 5.0%). Serious AEs reported were 13.7%/13.8% v. 2.5%.
March 28, 2016
GW Pharmaceuticals reported results of the first pivotal phase III study of Epidiolex (cannabidiol or CBD) for the treatment of Dravet syndrome. The study randomized 120 patients into two arms, Epidiolex 20mg/kg/day (n=61) and placebo (n=59). Epidiolex or placebo was added to current anti-epileptic drug (AED) treatment regimens. On average, patients were taking approximately three AEDs, having previously tried and failed an average of more than four other AEDs. The average age of trial participants was 10 years and 30% of patients were less than 6 years of age. The median baseline convulsive seizure frequency per month was 13. Patients taking Epidiolex achieved a median reduction in monthly convulsive seizures of 39% compared with a reduction on placebo of 13%, which was highly statistically significant (p=0.01). The difference between Epidiolex and placebo emerged during the first month of treatment and was sustained during the entire treatment period. Epidiolex was generally well-tolerated in the study. The most common adverse events (occurring in greater than 10% of Epidiolex-treated patients) were somnolence, diarrhea, decreased appetite, fatigue, pyrexia, vomiting, lethargy, upper respiratory tract infection and convulsion. Of those patients on Epidiolex that reported an adverse event, 84% reported it to be mild or moderate. GW is currently conducting a second phase III trial in Dravet syndrome, which is recruiting 150 patients. Epidiolex has both Orphan Drug designation and Fast Track designation from the FDA in the treatment of Dravet syndrome.
September 5, 2011
Eisai released preliminary results from a phase III trial of Zonegran for pediatrics with partial-onset seizures. This placebo-controlled study, CATZ, enrolled 207 subjects aged 6 to 17 who were already taking one or two antiepileptic drugs. Subjects were randomized to receive either Zonegran or placebo in addition to their existing medications. The primary endpoint was the proportion of subjects who responded to therapy by a 50% or more reduction in seizure frequency after 12 weeks of maintenance therapy. The results showed that 50.5% of subjects responded positively to the addition of Zonegran, compared with a response rate of 31% among the placebo group.
April 30, 2007
Addex issued positive results from a phase IIa trial of ADX10059 for the treatment of migraine headaches. This double-blind, placebo-controlled comparison trial enrolled 129 subjects in the United Kingdom and Germany. Subjects received a single dose of ADX10059 or placebo to treat a single moderate or severe (IHS Grade 2 or 3) migraine, in an outpatient setting. The primary endpoint was the proportion of subjects pain-free (IHS 0) two hours after dosing. This endpoint reached statistical significance, with 16.1% of the subjects taking ADX10059 pain-free compared to 4.5% of those taking placebo (p = 0.039). Improvement in migraine pain could be seen from 1 hour after dosing, with the compound being numerically superior to placebo at 1.0 and 1.5 hours post-dose. In addition, there were trends to superiority for ADX10059 over placebo for migraine pain improvement (mild or no pain) at all time points up to two hours post-dosing. Based on the results Addex plans to initiate phase IIb trials shortly.
Amarin reported negative results from two phase III trials of Miraxion for the treatment of Huntington's disease. These randomized, double-blind, placebo-controlled trials enrolled 600 subjects who received Miraxion 2g (1g twice daily) or placebo for six months. The primary endpoint was a change in the Total Motor Score 4 (TMS-4) component of the Unified Huntington's Disease Rating Scale (UHDRS). Secondary endpoints included cognition, behavioral and Total Functional Capacity outcomes. Data showed no statistically significant difference in either study between Miraxion and placebo with regard to the primary and secondary endpoints. Amarin plans to fully evaluate the data in order to determine a future course of action.
UCB announced positive top-line results from a phase III trial of Keppra for adjunctive therapy in the treatment of partial onset seizures in children. This double-blind, randomized, placebo-controlled study enrolled 116 children aged one month to four years. Subjects received Keppra (20-50 mg/kg/day) or placebo for five days. The primary endpoint was efficacy based on a 48 hour video EEG performed at baseline and at the end of the evaluation period. Results revealed 43.1% of Keppra-treated subjects experienced at least a 50% reduction in seizure frequency during the evaluation period compared with 19.6% of placebo-treated subjects. Treatment was generally well tolerated, with the most common adverse events somnolence and irritability. Based on the results UCB plans to file a sNDA with the FDA for Keppra as therapy in this population.