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 8, 2015
Eisai has issued results of a phase III study
of FYCOMPA (perampanel) CIII for Primary
Generalized Tonic-Clonic (PGTC) seizures
in patients age 12 and older. Results of the
phase III, randomized, double-blind, placebo-controlled
clinical trial of 162 patients, taking
one to three antiepileptic drugs, demonstrated
that patients treated with FYCOMPA (n=81)
achieved a 76% median reduction in PGTC
seizure frequency, which was statistically
significant compared to 38% with placebo
(n=81). Additionally, 64% of patients treated
with FYCOMPA experienced a 50% or greater
reduction in PGTC seizure frequency vs. 40%
with placebo, which also was statistically
significant. The most frequently reported
adverse events (>10% in the FYCOMPA group
and greater than placebo) in patients treated
with FYCOMPA in the phase III clinical trial
were dizziness, fatigue, headache, somnolence
and irritability. FYCOMPA recently was
approved by the FDA for adjunctive therapy in
the treatment of PGTC seizures in patients with
epilepsy age 12 and older.
March 4, 2013
Pfizer released results for a phase III trial of Lyrica (pregabalin) capsules CV compared to levetiracetam for the treatment of seizures. This randomized, double-blind, parallel-group, multi-center, comparative, flexible-dose study enrolled adult patients experiencing refractory partial onset seizures caused by epilepsy and who also were unresponsive to treatment with at least two, but no more than five, prior antiepileptic drugs. Subjects received Lyrica 300mg, 450mg or 600mg daily or levetiracetam 1,000mg, 2,000mg or 3,000mg daily for 12 weeks. The top-line results indicate the study met its primary endpoint by demonstrating a comparable proportion of patients on Lyrica achieved at least a 50% reduction in the 28-day seizure rate during the maintenance phase relative to levetiracetam. Lyrica was well tolerated. The most frequent adverse events were headache, dizziness, insomnia, somnolence, nausea and fatigue. Based on these results, Pfizer will be submitting data for presentation at upcoming scientific congresses and for publication in a peer-reviewed medical journal.
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.
Eisai reported results from a phase III trial of perampanel for partial-onset seizures. This global, randomized, double-blind, placebo-controlled study (305) enrolled 389 subjects who received 8 or 12 mg perampanel or placebo once daily for 19 weeks, on top of their regular therapy. The response rates, defined as 50 percent or greater reduction in seizure frequency, were 14.7% for placebo, 33.3% for 8mg (p≡0.002) and 33.9% for 12 mg (p≡<0.001). In addition. perampanel 8 mg and 12 mg once-daily reduced median seizure frequency by 30.5% and 17.6%, respectively versus 9.7% for placebo. The most common adverse events were dizziness, fatigue, headache and somnolence.
March 14, 2011
Vertex reported results from a phase II trial of VX-765 for epilepsy. This randomized, double-blind, placebo-controlled study enrolled 60 adults with treatment-resistant partial onset epilepsy. The subjects received VX-765 as a 300mg oral tablet three times a day (900mg total) or placebo, along with standard epilepsy treatment, for a six-week duration. The primary endpoints of safety and tolerability were reached. The secondary endpoints assessed the clinical efficacy and were based on the percent reduction in seizure frequency, percent of subjects with a 50 percent or greater reduction in seizure frequency (responder-rate) and percent of subjects who were seizure-free in the last two weeks of treatment. These endpoints were reached by 13% to 19% of the VX-765 arm versus 0% to 9% of the placebo arm.
March 9, 2009
Marinus reported positive results from a phase II trial of ganaxolone for the treatment of partial onset seizures. This randomized, double-blind, placebo-controlled trial enrolled 147 adults with partial onset seizures, who continued to have seizures even while taking up to three antiepileptic drugs. The subjects were observed for baseline seizure activity for eight weeks and were then randomized to receive either ganaxolone or placebo in addition to their existing stable AED regimen. The arm receiving ganaxolone were titrated over one to two weeks to a maintenance dose of 1,500 mg/day, where they were maintained for an additional eight weeks. The primary endpoint, a statistically significant reduction of mean weekly seizure frequency versus placebo, was reached during the titration and maintenance period (p<0.0251). Subjects in the ganaxolone arm also showed an improvement on percent reduction in seizure frequency versus placebo (p<0.0144). Responder rates (a greater than 50 percent reduction in seizures) were numerically higher in the ganaxolone arm versus placebo but did not reach statistical significance (p<0.1926). Ganaxolone was generally well tolerated. Based on the results, Marinus plans to move the development of ganaxolone into phase IIb studies.
May 26, 2008
Eisai issued results from a clinical study of rufinamide for the treatment of Lennox-Gastaut syndrome (LGS). This multi-center, double-blind, placebo-controlled, randomized, parallel-group study enrolled 139 subjects between the ages of four and thirty years who were being treated with one to three concomitant stable dose antiepileptic drugs (AEDs). The subjects received either rufinamide (titrated up to 45mg/kg per day) or placebo in addition to their other AEDs. The trial met all the primary endpoints. The median percentage reduction in total seizure frequency from baseline was greater in the rufinamide therapy group than in the placebo group (32.7% versus 11.7%; p<0.002). The rufinamide-treated subjects had 42.5% median percentage reduction in tonic-atonic seizure (drop attack) frequency per 28 days from baseline as compared with 1.4% increase in the placebo-treated subjects (p<0.0001). The rufinamide group had a statistically significant improvement in seizure severity (p<0.005) and a higher percentage of subjects who experienced at least a 50% reduction in tonic-atonic seizure frequency per 28 days compared with placebo (42.5% versus 16.7; p=0.002). Treatment was generally well tolerated. An NDA for rufinamide is currently under review.
May 19, 2008
Valeant issued positive results from a phase III trial of retigabine for the treatment of epilepsy. This international, randomized, double-blinded, placebo-controlled, parallel group study was dubbed RESTORE-2 (Retigabine Efficacy and Safety Trials for Partial Onset Epilepsy) and enrolled 539 subjects. All subjects had refractory partial-onset seizures despite receiving one, two or three ant-epileptic drugs. The subjects received retigabine in fixed doses of 600 and 900 mg/day, administered in three divided doses, or placebo for thirty weeks. The co-primary endpoints were reached with statistical significance. These were 1) the percentage change in total partial seizure frequency per four weeks from baseline to the double-blind period, and 2) the proportion of responders, defined as a patient experiencing a greater than or equal to 50 percent reduction in total partial seizure frequency per four weeks from baseline to the double-blind period. The median reductions in twenty-eight day total partial seizure frequency were 15.9%, 27.9% and 39.9% in the placebo and retigabine 600 and 900 mg arms, respectively (p less than 0.01). The responder rates were 17.3%, 31.5% and 39.3% for the placebo and retigabine 600 and 900 mg arms, respectively (p less than 0.01). Treatment was generally well tolerated. Based on positive phase III results Valeant plans to file an NDA with the FDA and an MAA with the EMEA before the end of 2008.
February 18, 2008
Valeant reported positive results from a phase III trial of retigabine for the treatment of epilepsy. This randomized, double-blinded, placebo-controlled, international, parallel group study was dubbed RESTORE-1 (Retigabine Efficacy and Safety Trials for Partial Onset Epilepsy). The study enrolled three hundred and six subjects with epilepsy who were experiencing refractory partial-onset seizures despite receiving one, two or three Anti-epileptic drugs. The treatment duration was thirty two weeks and consisted of a fixed dose of 1200 mg/day of retigabine, administered in three divided doses, or placebo. The following primary endpoints were reached with statistical significance. The median reduction in twenty eight day total partial seizure frequency was 44.3% in the retigabine arm compared to 17.5% in the placebo arm (p less than 0.0001). The median reduction in twenty eight day total partial seizure frequency during the maintenance phase was 54.5% in the retigabine arm compared to 18.9% in the placebo arm (p less than 0.0001). The responder rate, defined as greater than or equal to 50% reduction in twenty eight day total partial seizure frequency, was 45.0% and 18.0% for retigabine versus placebo, respectively, and the responder rate during maintenance phase was 55.5% and 22.6% for retigabine versus placebo, respectively, (p less than 0.0001). Additional phase III trials are currently underway and Valeant anticipates filing an NDA with the FDA and an MAA with the EMEA before the end of 2008.
December 10, 2007
UCB Pharma reported positive results from two phase II trials of lacosamide for the treatment of epilepsy. This double-blind, randomized, parallel-group, placebo-controlled study enrolled four-hundred and five subjects with refractory partial onset seizures, which were uncontrolled despite treatment with one to three anti-epileptic drugs. The subjects received lacosamide 400 mg/day or 600 mg/day (given in two doses), or placebo for twelve weeks. The median reduction in seizure frequency from baseline was significantly greater for lacosamide than placebo: 37.3%, 37.8% and 20.8% for lacosamide 400 mg/day, 600 mg/day, and placebo, respectively. Significantly more subjects achieved a 50% or greater reduction in seizure frequency with lacosamide than placebo: 38.3%, 41.2% and 18.3% for lacosamide 400 mg/day, 600 mg/day, and placebo, respectively. Nine subjects who completed the Maintenance Phase were seizure free throughout the entire twelve-weeks: four in the 400 mg/day group (2.5%) and five in the 600 mg/day group (8.1%). The subjects who completed the SP754 trial had the option to transition to an open-label extension study, which was designed to evaluate long-term the efficacy and safety profile of lacosamide. A total of three hundred and seventy subjects were enrolled and received a median lacosamide dose of 400 mg/day. Of the 370 subjects, 284 (76.8%) were exposed to lacosamide for more than twelve months, 224 (60.5%) for more than twenty-four months, and 140 (37.8%) for more than thirty six months. After 5.5 years the median percent reduction in seizure frequency across all prior treatment groups was 45.9%. Additionally, 46.6% of subjects had at least a 50% reduction in seizure frequency with lacosamide. The long-term use of lacosamide was determined to be safe and well tolerated. An NDA is currently under review by the FDA.