- Dr. Rajnish Dhediya [SYR] Guide: Dr. Shirish Joshi

Recent advances in the

treatment of Epilepsy

• Term epilepsy is derived from the Greek word “Epilamvanein or Epilepsia”, which means ‘to be seized’, ‘to be taken hold of’, or ‘to be attacked’

• Epilepsy: A condition in which a person has recurrent seizures due to chronic, underlying process

Characterized by,

- Recurrent seizures

- Loss of consciousness

- With or without body movements

• Seizure: “Paroxysmal event due to abnormal, excessive, hyper synchronous neuronal activity in the brain.”

Longo, Fauci, Kasper, Houser, Jamson, Loscalzo.Harrison’s principle of internal medicine:18 th edition, volume 1;Chapter-369

Talking about numbers….

• Second most common neurological disease

• 50 million people worldwide have epilepsy,

• 80% of epilepsy cases worldwide are found in developing regions

In India,

Incidence rate: 27.27 cases per year per 100,000 persons

Prevalence rate: 572.8 cases per 100,000 persons

1,81,000 new cases each yearDrug therapy successful in only 50%

Modified ILAE Classification

Partial Generalized

Seizure

Secondary gen.

TonicClonicTonic-clonicAbsenceAtonicMyoclonicAtypical absenceInfantile spasms

Complex Simple

Motor

Sensory

Autonomic

PsychicPanayiotopoulos C P. The new ILAE report on terminology and concepts for organization of epileptic seizures: a clinician's critical view and contribution. Epilepsia. 2011 Dec;52(12):2155-60

Pathophysiology of seizures

• No pathognomic lesion

• Hallmark is rhythmic and repetitive hyper synchronous discharge of neurons

• The regular low frequency neuronal discharges are replaced by bursts of high frequency discharges, usually followed by periods of inactivity.

• The diagnosis of epilepsy is mainly clinical, EEG and other investigations help, but cannot conclusively confirm or refute the diagnosis

Seizure SequenceBurst of action potentials

Hyper synchronization

Seizure Propagation

Seizure Initiation

Pathophysiology of seizures

Hyper-excitable state

Decreased inhibitory input:

GABA

Increased excitatory input:

GlutamateVoltage-gated ion channels in favour

of excitation

Therapeutic targets...

Lourence L.Brunton, Brause A .Chabner, Bjorn K,Knollmann, The pharmacological basis of therapeutics:12 th edition, Section II. Neuropharmacology, Chapter 21. Pharmacotherapy of the Epilepsies

Drugs acting on Na+ channel

Drugs acting on Ca+2 channels

Drugs enhancing GABAergic transmission

Antiepileptic drugs• Efficacy known• Less expensive• Easily available

• Hepatic enzyme induction/ inhibition

• Drug-drug interaction• Category D• Alters hormonal & vitamin levels

Antiepileptic drugs

Newer Antiepileptic drugs

Joseph Sirven, Katherine Noe, Mathew Hoerth, Joseph Drazkowski. Antiepileptic Drugs 2012: Recent Advances and Trends. Mayo Clinic Proceedings Vol 87, Issue 9 (879–889)

Newer Antiepileptic drugsDrugs Mechanism of

actionFDA approved indication

Lamotrigine Inhibits voltage sensitive sodium channels Inhibits synaptic release of glutamate

as adjunctive therapy of partial seizures in patients greater than or equal to 2 years of age and Primary GTC in patients ≥ 13 years of age

Levetiracetam Binds to synaptic vesicle protein SV2A and impedes nerve conduction

Refractory Partial seizuresRefractory JME

Gabapentin Binds to α2δ subunit of voltage gated calcium channels

Partial seizure with or without secondary generalization

Drugs Mechanism of action FDA approved indication

Lacosamide Sodium channel modulation

Add-on for partial epilepsy

Rufinamide Sodium channel modulation

Lennox-Gastaut syndrome in children 4 years and older and adultsAtonic seizures

Zonisamide Inhibition of sodium channels & T type of calcium channel currentsDecreases GABA uptake & increases glutamate uptake

Focal seizure

Vigabatrin Irreversible inhibitor of GABA transaminase

Infantile spasmsAs an adjunctive for refractory partial epilepsy

Newer Antiepileptic drugs

Advantages of Newer AEDs:

Greater tolerability

Fewer side effects

Fewer drug interactions

Lower rate of relapse after withdrawal

Fewer idiosyncratic reactions

Minimal influence on metabolic pathways

Category C

Joseph Sirven, Katherine Noe, Mathew Hoerth, Joseph Drazkowski. Antiepileptic Drugs 2012: Recent Advances and Trends. Mayo Clinic Proceedings Vol 87, Issue 9 (879–889)

Current treatmentSeizure type First line treatment Second line treatment

Partial seizures CarbamazepineLamotrigineOxcarbazepineLevetiracetam

TopiramateValproateClobazamZonisamide

Generalized seizures

Tonic-clonic Sodium ValproateCarbamazepine

LamotrigineClobazam

Absence EthosuximideSodium valproate

ClobazepamLamotrigine

Atypical absence ClobazepamClobazam

LamotrigineCarbamazepine

Myoclonic Sodium valproateClonazepam

LevitiracetamTopiramate

Need For Better AED’s ??

• No evidence that any new AED was superior in efficacy to old AEDs

Eg. CBZ and VPA in efficacy in well-controlled trials of recent-onset epilepsy.

• Although seizure control may have improved in rare epilepsies (Vigabatrin for West-Syndrome , Felbamate for LGS), but , seizure control has not improved dramatically in the last 30 years for common seizures (focal, myoclonic and absence)

• Further, one in three patients has drug resistant seizures.

Recent advances…

FDA approved drugs

New applications of existing drugs

New formulations in

pipeline

Drugs in pipeline

Recent FDA approvals

Clobazam

• Acts by potentiation of GABAnergic transmission via binding to GABA-A receptor

A benzodiazepine with low tendency to produce sedation Lower incidence of loss of therapeutic effect over time, rendering it

appropriate for long term management

• Oct 2011: FDA approved for Clobazam as adjunctive treatment for seizures associated with Lennox-Gestaut syndrome in adults and children 2 years of age and older in a dose of 5-40 mg/day.

Effectiveness was established in two multi-centre controlled studies.

• Most common adverse effects: sedation, lethargy and fatigue

In Dec 2013, FDA issued warning against serious skin

reactions that can result in permanent harm and death and

approved label changes

Ng YT, Conry JA, Drummond R, Stolle J, Weinberg MA; OV-1012 Study Investigators. Randomized, phase III study results of Clobazam in Lennox-Gastaut syndrome. Neurology. 2011 Oct 11;77(15):1473-81

Ezogabine

• First neuronal potassium channel opener developed for the

treatment of epilepsy

Acts by enhancement of potassium currents mediated by KCNQ ion

channels, thereby reducing hyper excitability

Also potentiates GABA-A receptors via activation of beta 1 & beta 2

subtype of GABA receptor

Also, weakly blocks sodium and calcium channels

Nov 2011: FDA approved Ezogabine as an adjunctive treatment in

refractory partial-onset seizures based on RESTORE I & II trials

Owen RT Ezogabine: a novel antiepileptic as adjunctive therapy for partial onset seizures. Drugs Today 2010 Nov;46(11):815-22

RESTORE 1 & 2(Retigabine Efficacy and Safety Trials for Partial Onset Epilepsy Study)

Brodie MJ, Lerche H, Gil-Nagel A, Elger C, Hall S, Shin P, Nohria V, Mansbach H; RESTORE 2 Study Group. Efficacy and safety of adjunctive ezogabine (retigabine) in refractory partial epilepsy. Neurology. 2010 Nov 16;75(20):1817-24

French JA, Abou-Khalil BW, Leroy RF, Yacubian EM, Shin P, Hall S, Mansbach H, Nohria V; RESTORE 1/Study Investigators. Randomized, double-blind, placebo-controlled trial of ezogabine (retigabine) in partial epilepsy. Neurology. 2011 May 3;76(18):1555-63

Ezogabine (Retigabine)• Absorption is unaffected by food with an absolute bioavailability of

50–60%• Peak plasma concentration within 1.5 h and half life is 8 – 11 hours

• Not metabolized by the cytochrome P450 system, so minimal drug interactions seen, as below,

Phenytoin & Carbamazepine decrease Ezogabine concentration Ezogabine inhibits renal clearance of digoxin Alcohol can increase serum Ezogabine concentrations

Serious adverse effects include urinary retention, neuropsychiatric symptoms and QT-interval lengthening that need careful monitoring

French J A et al. Randomized, double-blind, placebo-controlled trial of ezogabine (retigabine) in partial epilepsy. Neurology.2011 May 3; 76(18): 1555-63

Oxcarbazepine ER• Acts by blockade of voltage sensitive sodium channels Less potent enzyme inducer than carbamazepine

• Oct 2012: FDA approved a once-daily extended-release formulation as an adjunctive therapy for partial seizures in adults and in children > 6 years

• Dose: 1200 – 2400 OD on empty stomach

• PROSPER study, a multicentre, randomized, double-blind trial in 366 patients with refractory partial epilepsy showed efficacy

• Most common adverse effects include headache, dizziness and diplopia Rare and Serious adverse effects are hyponatremia and suicidal ideation

French JA, Baroldi P, Brittain ST, Johnson JK; PROSPER Investigators Study Group. Efficacy and safety of extended-release oxcarbazepine (Oxtellar XR™) as adjunctive therapy in patients with refractory partial-onset seizures: a randomized controlled trial. Acta Neurol Scand. 2014 Mar;129(3):143-53

Eslicarbazepine• Third generation AED

• S-licarbazepine: effective component of carbamazepine with,

fewer cognitive and psychiatric adverse effects

crosses BBB more effectively

lacks a toxic epoxide

minimal interaction with the cytochrome P450 liver enzymes

Elger et al. showed less incidence of hyponatremia compared to

oxcarbazepine

Elinor Ben-Menachem. Eslicarbazepine Acetate: A Well-Kept Secret? Epilepsy Curr. Jan 2010; 10(1): 7–8

• Acts by blockade of fast acting voltage gated sodium channels

• Nov 2013: US FDA approved as an adjunctive treatment for partial onset seizures

• Based on 3 randomized, double blind, multi-centre trials in 1049 patients with partial onset seizures

• Dose: 400-1200 mg/day ; once daily dosing

• Most adverse effects include headache, nausea, ataxia, tremors

Eslicarbazepine

Gil-Nagel A, Elger C, Ben-Menachem E, Halász P, Lopes-Lima J, Gabbai AA, Nunes T, Falcão A, Almeida L, da-Silva PS. Efficacy and safety of eslicarbazepine acetate as add-on treatment in patients with focal-onset seizures: integrated analysis of pooled data from double-blind phase III clinical studies. Epilepsia. 2013 Jan;54(1):98-107

Parampanel• First-in-class drug, a highly selective, non competitive AMPA type

glutamate receptor antagonist

• Nov 2012: FDA approved for treatment of refractory partial-onset seizures in patients 12 years and older,

based on 3 clinical trials in 1037 adults and adolescents which showed reduced seizure frequency

Dose: 4 – 12 mg OD

• Boxed warning about the risk for serious neuropsychiatric events

• Common adverse effects include dizziness, fatigue, irritability, anxiety, aggression, etc

Steinhoff BJ, Ben-Menachem E, Ryvlin P, Shorvon S, Kramer L, Satlin A, Squillacote D, Yang H, Zhu J, Laurenza A. Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: a pooled analysis of three phase III studies. Epilepsia. 2013 Aug;54(8):1481-9

Topiramate –extended release

Blockage of voltage-dependent sodium channels

Augmentation of the activity of the neurotransmitter GABA

Antagonism of the AMPA/ kainate subtype of the glutamate

receptor

• March 2014: US FDA approved

As monotherapy for focal seizure and primary GTC in patients >

10 years and,

As an adjunctive therapy in patients > 2 years for focal seizures,

primary GTC and seizures associated with Lennox-Gestaut

syndrome.

• Phase III PREVAIL study in 249 patients with partial-onset seizures,

• PREVAIL study demonstrated - efficacy - improved seizure control - Less cognitive side effects

• Dose: 400 mg OD

• Adverse effects include dizziness, weight loss, paraesthesia etc.

Topiramate –extended release

Chung SS, Fakhoury TA, Hogan RE, Nagaraddi VN, Blatt I, Lawson B, Arnold S, Anders B, Clark AM, Laine D, Meadows RS, Halvorsen MB; PREVAIL Study Group. Once-daily USL255 as adjunctive treatment of partial-onset seizures: randomized phase III study. Epilepsia. 2014 Jul;55(7):1077-87

Drugs in pipeline

Drugs decreasing neuronal excitation

A. Blockade of sodium channel• Brivaracetam• Carisbamate

B. Inhibition of glutamate release/ AMPA antagonist• NS 1209• BGG 492

Drugs enhancing neuronal inhibition

• Ganalaxone

• Stiripentol

• CPP 115

• Valrocemide

Drugs in pipeline

Drugs in pipelineNovel agents

1. Anti-inflammatory: Belnacasan (VX 765)

2. Pro-drug of Valproic acid: SPD 421, Valnoctamide

3. Chloride importer blockade: Bumetanide

4. Drugs acting on potassium channels

• YKP 3089

• ICA 105665

5. Melatonin

6. 5HT receptor agonist: Naluzotan

Brivaracetam

• Levetiracetam analogue

• 10-fold greater affinity for synaptic vesicle protein 2α (SV2α)

ligand than does Levetiracetam

• Additional sodium channel-blocking properties

• Preclinical study suggested potent and broad spectrum

antiepileptic activity

• Currently in phase III for partial onset seizure

Biton V, Berkovic SF, Abou-Khalil B, Sperling MR, Johnson ME, Lu S. Brivaracetam as adjunctive treatment for uncontrolled partial epilepsy in adults: a phase III randomized, double-blind, placebo-controlled trial. Epilepsia. 2014 Jan;55(1):57-66

Carisbamate (RWJ 333369)

• Novel neuromodulator

• Proposed mechanism of action: Inhibit voltage gated sodium channel & modest inhibition of voltage gated calcium channel

• Phase II study- adjunctive use in partial onset seizures showed efficacy at a well tolerated dose

• Phase III study in 2011 for focal seizure failed to demonstrate efficacy across the dose range assessed versus placebo.

A Study of the Effectiveness, Safety, and Tolerability of Carisbamate as Add-On Therapy in Patients With Partial Onset Seizures. http://clinicaltrials.gov/show/NCT00740623 (accessed 21 Nov 2014)

1. NS 1209AMPA antagonists

• Novel competitive AMPA antagonist

• Phase II study in patients with refractory status epilepticus failed to

reach study end point

2. BGG 492• Orally active AMPA antagonist

• Very favourable safety profile is evidence by a lack of

cardiovascular, phototoxic or teratogenicity potential

• Currently in phase II for focal seizure & photosensitive epilepsy

Global Journal of Medical Research: B Pharma, Drug Discovery, Toxicology and Medicine. Volume 14 Issue 4 Version 1.0 Year 2014

Ganaxolone

• A neurosteroid with ability to modulate neurotransmission

• Acts as positive allosteric modulator of γ-amino butyric acid GABA- A receptors

• Phase II (2009) trial: shown beneficial role in refractory focal seizure

• Currently in phase III for drug resistant focal seizure- Recruiting participants

Phase 3 Study of Adjunctive Ganaxolone in Adults With Drug-resistant Partial Onset Seizures, With Long-term Open-label Extension. http://www.clinicaltrials.gov/show/NCT01963208. (accessed 21 Nov 2014)

Pieribone VA, Tsai J, Soufflet C, Rey E, Shaw K, Giller E, Dulac O. Clinical evaluation of ganaxolone in pediatric and adolescent patients with refractory epilepsy. Epilepsia. 2007 Oct;48(10):1870-4

Stiripentol• Increase γ-amino butyric acid (GABA) levels in brain tissue

• Involves at least two independent neurochemical mechanisms: Inhibition of synaptosomal uptake of GABAInhibition of GABA transaminase

• Phase III- Childhood focal seizure-Failed to achieve primary end point

• Currently undergoing Expanded Access study for Dravet Syndrome or Sodium Channel Mutation Epileptic Encephalopathy

Chiron C1, Tonnelier S, Rey E, Brunet ML, Tran A, d'Athis P, Vincent J, Dulac O, Pons G. Stiripentol in childhood partial epilepsy: randomized placebo-controlled trial with enrichment and withdrawal design. J Child Neurol. 2006 Jun;21(6):496-502.

CPP 115• Analogue of Vigabatrin with favourable pharmacokinetics

• Acts by irreversible inhibition of GABA transaminase, enzyme

responsible for metabolism of inhibitory neurotransmitter GABA

• Superior efficacy in an infantile spasms model

• Minimal drug-drug interaction with good safety profile

• Received orphan drug designation for infantile spasms

• Phase I studies: well-tolerated at doses upto 500 mg

• Currently in Phase II for Refractory complex focal seizures

Briggs SW, Mowrey W, Hall CB, Galanopoulou AS. CPP-115, a vigabatrin analogue, decreases spasms in the multiple-hit rat model of infantile spasms. Epilepsia. 2014 Jan;55(1):94-102

A Safety, Tolerability and Pharmacokinetic Study of CPP-115. http://clinicaltrials.gov/show/NCT01493596 (accessed 20 Nov 2014)

Valrocemide

• Amide derivative of valproic acid

• Mechanism of action : Potentiation of gabanergic current by

binding to GABA receptor

• Phase I : Safe, Relative bioavailabily-88 %

• Phase II : showed efficacy of Valrocemide as an adjunctive

therapy in refractory epilepsy patients

• Phase III: Presently Ongoing in patients with refractory epilepsy

Hovinga CA. Valrocemide (Teva/Acorda). Curr Opin Investig Drugs. 2004 Jan;5(1):101-6.

Belnacasan (VX 765)

• Proposed involvement of inflammatory mechanisms in the

generation of epileptic discharges

• Belnacasan inhibits Interleukin converting enzyme/ Caspase 1 and

thereby production of cytokines

• Following exposure to pro-inflammatory stimuli, the release of IL-1β

in hippocampus is reduced, thereby preventing acute seizures

Lauren Walker, Graeme JS. Inflammation and Epilepsy: The Foundations for a New Therapeutic Approach in Epilepsy? Epilepsy Curr. 2012 Jan-Feb;12(1): 8–12

• Efficacy is confirmed in preclinical models

Phase IIa trial in drug-resistant partial epilepsy suggest that

Belnacasan is safe and well tolerated when administered

over a 6-week period

Phase IIb trial in patients with treatment-resistant epilepsy is

currently ongoing

Belnacasan (VX 765)

Study of VX-765 in Subjects With Treatment-resistant Partial Epilepsy. http://clinicaltrials.gov /ct2/show /NCT01048255. (accessed 18 Nov 2014)

• Phospholipid derivative of valproic acid

• It is a pro-drug based on Regulated activation of pro-drugs (RAP)

technology, to overcome unfavourable pharmacokinetics of

valproic acid

• Multinational phase II trials of SPD-421 as add-on therapy in the

treatment of complex partial seizures reported positive results

• Adverse effects are minimal compared to Valproate

Valnoctamide, an amide derivative of Valproate, has a potential in epilepsy and is currently being investigated in Phase I trials

Labiner DM. DP-VPA D-Pharm. Curr Opin Investig Drugs.2002 Jun; 3(6): 921-3

Bumetanide

• A loop diuretic, blocks the Na–K–2Cl co-transporter in neurons,

the concentration change making the action of GABA more

hyperpolarizing

• Preclinical studies have shown promising results

• A pilot study demonstrated reduction of seizure frequency in

adult patients with temporal lobe epilepsy

• A Phase I Study of Pharmacokinetics and Safety of Bumetanide

for Neonatal Seizures is currently ongoing

• Eftekhari S et al. Bumetanide reduces seizure frequency in patients with tempo al lobe epilepsy. Epilepsia. 2013 Jan; 54(1):9-12

• Wolfgang Lösche. Martin Puskarjov. Kai Kaila. Cation-chloride cotransporters NKCC1 and KCC2 as potential targets for novel antiepileptic and antiepileptogenic treatments. Neuropharmacology. Vol. 69,June 2013, pg.62–74

Potassium channels modulators

YKP 3089

• Novel, broad spectrum anti-epileptic

• Mechanism of action is not yet defined, possibly act by

increased KCN Q 2/3 type of potassium current

• High safety margin in phase I study

• Phase II study is ongoing for focal seizures.

Meir Bialera, Svein I, Johannessen , René H. Levyd, Emilio Peruccae, Torbjörn Tomsonf, H. Steve White. Progress report on new antiepileptic drugs: Asummary of the Tenth Eilat Conference (EILAT X). Epilepsy Research (2010) 92, 89—124

Potassium channels modulators

ICA 105665

• Agonist of neuronal Kv7 potassium channels

• Phase I- Safe

• In 2010, a Phase 2, multi-centre study was terminated

following a SAE that occurred with the first subject dosed at

600 mg

A Study to Investigate the Effect of ICA-105665 in Photosensitive Epilepsy Patients. http://clinicaltrials.gov/show /NCT00979004 (accessed 18 Nov 2014)

Melatonin

• Baseline melatonin levels are low in patients with uncontrolled

epilepsy and increase markedly following seizures

• Melatonin modulates the electrical activity of neurons by reducing

glutamatergic and enhancing GABA-ergic neurotransmission and

experimental data indicates anticonvulsant properties of the

hormone

• ‘Pilot Study of Melatonin and Epilepsy’ completed in June 2014

Banach M. Gurdziel E. Jędrych M, Borowicz KK. Melatonin in experimental seizures and epilepsy. Pharmacol Rep. 2011; 63(1): 1-11

Naluzotan

• Orally active selective 5-HT-1A receptor partial agonist

• Proposed mechanism of epileptogenesis is reduced 5-HT-1A receptor binding

• Naluzotan acts by increasing neurotransmitter activity at 5HT-1A receptor, thereby reducing seizure incidence and severity

• Phase I study revealed Naluzotan as safe & well tolerated

• Currently, Phase 2 trial is ongoing in patients with epilepsy

New Formulations

Intranasal • diazepam • midazolam (USL 261)

Diazepam auto injection

Advantages:

Absorption from nasal mucosa

within 2 – 5 minutes

Rapid penetration into the

central nervous system

Studies reveal superiority over diazepam for quickness of response

and ease of administration

Cost effective and feasible to administer to adults as well

Intranasal formulations

Lesley K. Humphries. Lea S. Eiland. Treatment of Acute Seizures: Is Intranasal Midazolam a Viable Option? J P ediatr Pharmacol Ther. 2013 Apr-Jun; 18(2): 79–87

Midazolam (USL 261)

Phase II: Single doses up to 7.5mg were well-tolerated with no significant adverse events

ARTEMIS1: Phase 3 study to Evaluate the Safety and Efficacy of Intranasal Midazolam in Patients With Seizure Clusters is currently ongoing.

Diazepam

Phase I study showed intranasal diazepam is safe with a bioavailability of 97%

Intranasal formulations

Study to Evaluate the Safety and Efficacy of USL261 (Intranasal Midazolam) in Patients with Seizure Clusters (ARTEMIS1). http://www.clinicaltrials.gov /show /NCT01390220. (accessed 20 Nov 2014)Thakker A1, Shanbag P. A randomized controlled trial of intranasal-midazolam versus intravenous-diazepam for acute childhood seizures. J Neurol. 2013 Feb;260(2):470-4

Diazepam auto injection • Pen-like device that injects medication intramuscularly

• Phase I & II : Safe & effective at stopping acute repetitive or cluster seizures

• July 2014: Phase III in 234 patients with refractory epilepsy having acute repetitive seizures showed diazepam AI was significantly more effective than placebo AI at delaying the next seizure or rescue

Abou-Khalil B et al. A double-blind, randomized, placebo-controlled trial of a diazepam autoinjector administered by caregivers to patients with epilepsy who require intermittent intervention for acute repetitive seizures. Epilepsia. 2013 Nov ; 54(11): 1968-76

New applications of existing drugs

LevetiracetamApproved for focal seizure and juvenile myoclonic epilepsy

Generalized tonic clonic seizures

Status epilepticus

Phase III

Rufinamide• Approved as adjunctive treatment of seizures associated with LGS

syndrome in children > 4 years

• Currently Phase III trial is ongoing to evaluate Rufinamide in paediatric subjects 1-4 years of age

Lacosamide

Approved as adjunctive therapy in the treatment of partial-onset seizures in patients > 17 years

• Phase IV completed in August 2013-positive result

Monotherapy for patients with partial-

onset seizures

• Phase II, open-label trial- OngoingAdjunctive therapy in paediatric population(1 month – 17 years of

age)

• Phase II, open-label trial-Completed in august 2011 with significant results

Adjunctive therapy in primary generalized tonic-clonic seizures

Conclusions :

Epilepsy is a treatable disorder, goal of treatment should be “no

seizures and least side-effects”.

Although current AEDs are helpful, serious unmet needs

continue to exist with regards to disease modifications

However now there are promising treatments in early and later

stages of clinical development.