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On August 25, Takeda and Ovid Therapeutics announced that ELEKTRA, a phase 2 clinical study used to treat children with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), had reached its primary endpoint and was highly statistically significant.
ELEKTRA is an international multi-center, randomized, double-blind, placebo-controlled Phase 2 clinical study designed to assess the therapeutic effects of soticlestat on children aged 2-17 with highly refractic seizures with DS (convulsive seizures) or LGS (falls).
the study included a screening period of 4-6 weeks to determine the frequency of baseline seizures, followed by a 20-week double-blind treatment period, including an 8-week dose optimization period and a 12-week maintenance period.
during the 8-week dose optimization period, patients were titration from oral soticlestat 100mg twice daily (BID), 200mg BID to 300mg BID (mg/kg dose in patients with .lt;60 kg).
141 patients were included in the study and 126 completed the study.
improved intent therapy (mITT) analysis of 139 patients was conducted to assess the end of the treatment, and the patients in the study were allowed to take 1-4 combined anti-epileptic drugs (AEDs), with the majority taking at least three AEDs at the same time, most commonly sodium valproate, chlorbazzam, L-ethyl iracetamate and topilatide.
data from 120 epilepsy patients in the efficacy-based analysis set showed that the median frequency of convulsive seizures (in DS) and falls (LGS) was compared to patients taking a placebo during the 12-week session The median frequency of convulsive seizures and falls decreased by 27.8%, while the median frequency of convulsive seizures and falls increased by 3.1% in placebo group patients (the median adjusted data for the placebo group decreased by an average of 30.5% ;p to 0.0007).
In addition, the median frequency of convulsive and fall seizures in patients treated with soticlestat decreased by 29.8% over the course of the study's 20-week (titration plus maintenance) treatment, while the median frequency of seizures decreased by 0.0% in the placebo group (25.1% after placebo adjustment ;p to 0.0024).
The median frequency of convulsive seizures in patients treated with soticlestat decreased by 33.8% over the entire study period in the DS queue study (n-51), while the median in the placebo group increased by 7.0% (placebo adjusted by 46.0% ;p-0.0007).
the data, the two companies plan to meet with drug regulators to discuss launching a registration program for Phase 3 clinical studies in DS patients.
the median frequency of falls in patients treated with soticlestat decreased by 20.6 percent over the entire study period in the LGS queue study (n-88), while the placebo group decreased by 6.0 percent (placebo adjusted by 14.8 percent ;p-0.1279).
the queue is currently undergoing more analysis to better understand the next steps in developing soticlestat in this highly heterogeneic patient population.
addition, soticlestat has demonstrated good overall tolerance in ELEKTRA studies, and its safety is consistent with previous studies, with no new safety signals found.
most common adverse events caused by treatment are drowsiness and constipation.
rates of severe adverse events in the Soticlestat and placebo groups (15.5% vs 18.6%) were similar, with no deaths reported.
but all patients who completed the ELEKTRA study continued an extended open-label study that will look at the safety and toerability of soticlestat over a four-year period and will also assess the long-term effects of the drug on seizure frequency.
DS and LGS are the types of developmental and epileptic encephalopathy (DEEs), a group of rare epilepsy syndromes that usually become apparent in inflamed or early childhood and are highly insensitive to many antiplateletes.
DS is most commonly caused by mutations in the SCN1A gene, characterized by prolonged onset seizures, which can evolve into spastic, strong, straight-on seizures, and an increase in seizures in children with developmental disorders.
other common symptoms include changes in appetite, difficulty balancing, and bending over while walking.
LGS is a heterogeneic disease characterized by several different types of epilepsy, the most common being muscle tensionless (falls), strongness and atypical seizures.
children with the disease may also experience cognitive dysfunction, delayed developmental milestones, and behavioural problems.
LGS can be caused by a variety of potential conditions, but in some cases the cause cannot be determined.
Soticlestat is an efficient, highly selective cholesterol 24 hydroxyase (CH24H) level 1 inhibitor with the potential to reduce epilepsy susceptibility and improve epilepsy control.
Recent literature has shown that CH24H involves overactivation of glutamate pathways by regulating the NMDA channel, and increased expression of CH24H can disrupt the re-ingestion of glutamate by star glial cells, leading to epilepsy and neurotoxicity.
soticlestat's inhibition of CH24H reduces neuron levels at 24HC and may improve the excitement/suppression balance of the NMDA channel.
Ovid and Takeda are studying soticlestat for the treatment of rare, highly incurable DEEs, including DS and LGS.
FORCADE for two other highly incurable DEEs, CDKL5 deficiency and Dup15q syndrome patients in open-label Phase 2 clinical studies, may be released later this quarter.
the two companies will share the development and commercialization costs and profits of soticlestat at a 50 per cent rate each.
is understood to have received FDA approval this year for two drugs to treat DS, including GW Pharma's cannabis-based extract Epidiolex and Zogenix's Fentepla.
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