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Novel Antiepileptic Drugs

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Novel Antiepileptic Drugs NOTE: To change the image on this slide, select the picture and delete it. Then click the Pictures icon in the placeholder to insert your own image. NOVEL ANTIEPILEPTIC DRUGS Amr Hassan M.D.,FEBN Associate professor of Neurology - Cairo University Antiepileptic drug development eslicarbazepine Perampanel Retigabine Rufinamide Vigabatrin 20 Lacosamide Pregabalin Zonisamide Levetiracetam Levetiracetam Tiagabine Oxcarbazepine 15 Topiramate Fosphenytoin Lamotrigine Gabapentin 10 Felbamate Sodium Valproate Carbamazepine Ethosuximide Benzodiazepines 5 Phenytoin Phenobarbital Primidone Bromide Number of Licensed Antiepileptic Antiepileptic Drugs of Licensed Number 0 1840 1860 1880 1900 1920 1940 1960 1980 2000 Calendar Year 2 Do we need more new epilepsy drugs? Seizure control New drugs Safety/tolerability Compliance OD dosing, XR formula ARS and SE Rapid drug delivery Detection and New Devices Prediction of seizures How do we make progress? Evolutionary Drugs • Improve on existing drugs Revolutionary Drugs • Drugs that work with new mechanisms never tried before 4 Epilepsy’s new pipeline therapeutics Marketed New Drugs Under Trial New route Marketed (Enhanced Drug Under Trial Delivery) Dietary Supplement Marketed New Therapeutic Devices Under Trial New in Egyptian Market 5 Epilepsy’s new pipeline therapeutics Marketed New Drugs Under Trial New route Marketed (Enhanced Drug Under Trial Delivery) Dietary Supplement Marketed New Therapeutic Devices Under Trial New in Egyptian Market 6 Brivaracetam (BRV) Company: UCB Approval Status: Approved February 2016 7 Brivaracetam (BRV): Mechanism of Action Brivaracetam Inhibitory synapse Excitatory synapse 8 Brivaracetam (BRV) • A novel high-affinity synaptic vesicle protein 2A (SV2A) ligand. • Also displays inhibitory activity at neuronal voltage- dependent sodium channels. • Adjunctive treatment of adults with POS. 1.Kenda et al. J Med Chem 2004;47:530–549 2.Zona et al. Epilepsy Res 2010;8846–54 9 Brivaracetam (BRV): (Briviact) 10 Brivaracetam (BRV) Levetiracetam • Company: Aprecia Pharmaceuticals Company • Approval Status: Approved August 2015 • a 3D printed drug product 12 ZipDose Technology using 3D printing: How it’s made 13 Levetiracetam (Spritam) 14 Topiramate Extended-Release Formulation Company: Upsher-Smith Laboratories Approval Status: Approved March 2014 Specific Treatments: • Partial onset and primary generalized tonic-clonic seizures • Lennox-Gastaut Syndrome 15 Topiramate Extended-Release Formulation (Qudexy XR ) 16 Eslicarbazepine Acetate (Aptiom) • Company: Sunovion Pharmaceuticals • Approval Status: Approved November 2013 • Indications: Partial-onset seizures 17 Eslicarbazepine Acetate : Mechanism of Action Eslicarbazepine Inhibitory synapse Excitatory synapse 18 Oxcarbazepine extended release • Company: Supernus Pharmaceuticals • Approval Status: Approved October 2012 • Indications: Partial seizures in adults and in children 6 years to 17 years of age 19 Oxcarbazepine extended release (Oxtellar XR ) 20 Perampanel • Company: Eisai Inc. • Approval Status: Approved October 2012 • Indications: Partial-onset seizures 21 Perampanel Perampanel Inhibitory synapse Excitatory synapse 22 Perampanel (Fycompa®) 23 Perampanel (Fycompa®) •Serious Psychiatric Changes •Behavioral Changes •Homicidal Or Suicidal Thoughts. Ezogabine = Retigabine • Company: Valeant Pharmaceuticals • Approval Status: Approved June 2011 • Indications: Partial-onset seizures 25 Retigabine: Mechanism of Action Retigabine Retigabine Inhibitory synapse Excitatory synapse 26 Ezogabine = Retigabine (Potiga) 27 Rufinamide • Company: Eisai Medical Research Inc. • Approval Status: Approved November 2008 • Specific treatments: Lennox-Gastaut Syndrome 28 Rufinamide 29 Rufinamide: Mechanism of Action Rufinamide Inhibitory synapse Excitatory synapse 30 Rufinamide (Banzel) 31 Epilepsy’s new pipeline therapeutics Marketed New Drugs Under Trial New route Marketed (Enhanced Drug Under Trial Delivery) Dietary Supplement Marketed New Therapeutic Devices Under Trial New in Egyptian Market 32 Epilepsy’s new pipeline therapeutics Marketed New Drugs Under Trial New route Marketed (Enhanced Drug Under Trial Delivery) Dietary Supplement Marketed New Therapeutic Devices Under Trial New in Egyptian Market 33 Seletracetam(SEL) 34 Selurampanel • Phase II. • a competitive antagonist of the AMPA and kainate receptors. • It has also been studied in the acute treatment of migraine(some pain relief, but with a relatively high rate of side effects 35 Bumetanide NKCC1 inhibition Neonatal seizures 36 Cannabidiol (Epidiolex) March 14, 216 (GLOBE NEWSWIRE) Dravet syndrome 37 Stiripentol (Diacomit) Company: Laboratoires Biocodex Approval Status: Not FDA approved Specific treatments: Dravet syndrome Stiripentol increases GABAergic activity. It enhances central GABA neurotransmission through a barbiturate-like effect. 38 Ganaxolone PCDH 19 female pediatric epilepsy 39 PCDH 19 female pediatric epilepsy • Serious and rare epileptic syndrome. • An inherited mutation of the protocadherin 19 (PCDH19) gene (X chromosome). • Early-onset cluster seizures, cognitive and sensory impairment and behavioral disturbances. 40 IV Ganaxolone April 15, 2016 Status epilepticus 41 Synthetic Huperzine A • Company:Biscayne ph • Derived from Chinese plant Chinese club moss • AchEI • Phase II 2016 CPS • Phase II 2017 Dravet syndrome 42 AED vs AEG AED AED VS AEG AEG 43 Gene expression Signaling pathways Epigenetics (ICER) BDNF REST cAMP response miRNA element JAK-STAT mTOR (CREB) Gene expression Signaling pathways Epigenetics (ICER) BDNF REST cAMP response miRNA element JAK-STAT mTOR (CREB) AEG Epilepsy’s new pipeline therapeutics Marketed New Drugs Under Trial New route Marketed (Enhanced Drug Under Trial Delivery) Dietary Supplement Marketed New Therapeutic Devices Under Trial New in Egyptian Market 52 52 Epilepsy’s new pipeline therapeutics Marketed New Drugs Under Trial New route Marketed (Enhanced Drug Under Trial Delivery) Dietary Supplement Marketed New Therapeutic Devices Under Trial New in Egyptian Market 53 53 IV Carbamazepine (Carnexiv) • Company: Lundbeck • Approval Status: Approved October 2016 • Lundbeck plans to make Carnexiv commercially available in the United States in early 2017. 54 Intrabuccal midazolam (epistatus) 55 Diazepam rectal gel (Diastat) 56 Diazepam auto-injector Diazepam auto-injector 58 Epilepsy’s new pipeline therapeutics Marketed New Drugs Under Trial New route Marketed (Enhanced Drug Under Trial Delivery) Dietary Supplement Marketed New Therapeutic Devices Under Trial New in Egyptian Market 59 59 Epilepsy’s new pipeline therapeutics Marketed New Drugs Under Trial New route Marketed (Enhanced Drug Under Trial Delivery) Dietary Supplement Marketed New Therapeutic Devices Under Trial New in Egyptian Market 60 60 Inhaled alprazolam • Originator Alexza Pharmaceuticals • Mechanism of Action GABA A receptor agonists • Phase II 61 Staccato technology 62 Transdermal CBD gel ZYN002 63 Transdermal cannabidiol (CBD) gel 64 Intranasal midazolam 65 Intranasal Diazepam(Neurelis) 66 Epilepsy’s new pipeline therapeutics Marketed New Drugs Under Trial New route Marketed (Enhanced Drug Under Trial Delivery) Dietary Supplement Marketed New Therapeutic Devices Under Trial New in Egyptian Market 67 67 Epilepsy’s new pipeline therapeutics Marketed New Drugs Under Trial New route Marketed (Enhanced Drug Under Trial Delivery) Dietary Supplement Marketed New Therapeutic Devices Under Trial New in Egyptian Market 68 68 Triheptanoin in GLUT1 deficiency GDD • Epilepsy • Movement • disorders 69 Triheptanoin in GLUT1 deficiency 70 Epilepsy’s new pipeline therapeutics Marketed New Drugs Under Trial New route Marketed (Enhanced Drug Under Trial Delivery) Dietary Supplement Marketed New Therapeutic Devices Under Trial New in Egyptian Market 71 71 Epilepsy’s new pipeline therapeutics Marketed New Drugs Under Trial New route Marketed (Enhanced Drug Under Trial Delivery) Dietary Supplement Marketed New Therapeutic Devices Under Trial New in Egyptian Market 72 72 Responsive Neurostimulation • FDA Approved November 2013 • Adjunctive treatment for adults with medically refractory partial seizures Epilepsy Alarm Bed Seizure Detection Anti-Suffocation Pillows Watches Epilepsy’s new pipeline therapeutics Marketed New Drugs Under Trial New route Marketed (Enhanced Drug Under Trial Delivery) Dietary Supplement Marketed New Therapeutic Devices Under Trial New in Egyptian Market 77 77 Epilepsy’s new pipeline therapeutics Marketed New Drugs Under Trial New route Marketed (Enhanced Drug Under Trial Delivery) Dietary Supplement Marketed New Therapeutic Devices Under Trial New in Egyptian Market 78 78 Trigeminal nerve stimulation (TNS) 79 Epilepsy’s new pipeline therapeutics Marketed New Drugs Under Trial New route Marketed (Enhanced Drug Under Trial Delivery) Dietary Supplement Marketed New Therapeutic Devices Under Trial New in Egyptian Market 80 80 Epilepsy’s new pipeline therapeutics Marketed New Drugs Under Trial New route Marketed (Enhanced Drug Under Trial Delivery) Dietary Supplement Marketed New Therapeutic Devices Under Trial New in Egyptian Market 81 81 Eslicarbazepine acetate chemical structure IV Lacosamide IV Levetiracetam Levetiracetam: Mechanism of action Levetiracetam Inhibitory synapse Excitatory synapse 85 Epilepsy’s new pipeline therapeutics Marketed New Drugs Under Trial New route Marketed (Enhanced Drug Under Trial Delivery) Dietary Supplement Marketed New Therapeutic Devices Under Trial New in Egyptian Market 86 86 DO WE NEED MORE NEW EPILEPSY DRUGS? Seizure control New drugs Safety/tolerability Compliance OD dosing, XR formula ARS and SE Rapid drug delivery Detection and New Devices Prediction of seizures Overcoming challenges !! 88 THANK YOU [email protected].
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