Seizure control New Antiepileptic drugs

1. Amr Hassan M.D.,FEBN
Associate professor of Neurology - Cairo University
NOVEL ANTIEPILEPTIC DRUGS

2. Antiepileptic drug development
1840 1860 1880 1900 1920 1940 1960 1980 2000
0
5
10
15
20
Bromide
Phenobarbital
Phenytoin Primidone
Ethosuximide
Sodium Valproate
Benzodiazepines
Carbamazepine
Zonisamide
Felbamate
Gabapentin
Topiramate Fosphenytoin
OxcarbazepineTiagabine
Levetiracetam
Rufinamide
Lacosamide Pregabalin
Calendar Year
NumberofLicensedAntiepilepticDrugs
Lamotrigine
Vigabatrin
Perampanel
Retigabine
Levetiracetam
eslicarbazepine
2

3. Seizure control
Safety/tolerability
Compliance
ARS and SE
Detection and
Prediction of
seizures
New Devices
New drugs
OD dosing, XR formula
Rapid drug delivery
Do we need more new epilepsy drugs?

4. How do we make progress?
4
Evolutionary Drugs
• Improve on existing drugs
Revolutionary Drugs
• Drugs that work with new mechanisms never
tried before

5. Epilepsy’s new pipeline therapeutics
5
New Drugs
New route
(Enhanced Drug
Delivery)
Dietary Supplement
New Therapeutic
Devices
New in Egyptian Market
Marketed
Marketed
Marketed
Under Trial
Under Trial
Under Trial

6. Epilepsy’s new pipeline therapeutics
6
New Drugs
New route
(Enhanced Drug
Delivery)
Dietary Supplement
New Therapeutic
Devices
New in Egyptian Market
Marketed
Marketed
Marketed
Under Trial
Under Trial
Under Trial

7. UCB:Company
Approval Status: Approved February 2016
Brivaracetam (BRV)
7

8. Brivaracetam (BRV): Mechanism of Action
Inhibitory synapse Excitatory synapse
Brivaracetam
8

9. 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

10. Brivaracetam (BRV): (Briviact)
10

11. Brivaracetam (BRV)

12. Levetiracetam
• Company: Aprecia Pharmaceuticals Company
• Approval Status: Approved August 2015
• a 3D printed drug product
12

13. ZipDose Technology using 3D printing: How it’s made
13

14. Levetiracetam (Spritam)
14

15. Topiramate Extended-Release Formulation
15
Company: Upsher-Smith Laboratories
Approval Status: Approved March 2014
Specific Treatments:
• Partial onset and primary generalized tonic-clonic
seizures
• Lennox-Gastaut Syndrome

16. Topiramate Extended-Release Formulation
(Qudexy XR )
16

17. Eslicarbazepine Acetate (Aptiom)
• Company: Sunovion Pharmaceuticals
• Approval Status: Approved November 2013
• Indications:
 Partial-onset seizures
17

18. Eslicarbazepine Acetate : Mechanism of Action
Inhibitory synapse Excitatory synapse
Eslicarbazepine
18

19. 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

20. Oxcarbazepine extended release (Oxtellar XR )
20

21. Perampanel
• Company: Eisai Inc.
• Approval Status: Approved October 2012
• Indications:
 Partial-onset seizures
21

22. Inhibitory synapse Excitatory synapse
Perampanel
22
Perampanel

23. Perampanel (Fycompa®)
23

24. •Serious Psychiatric Changes
•Behavioral Changes
•Homicidal Or Suicidal Thoughts.
Perampanel (Fycompa®)

25. Ezogabine = Retigabine
• Company: Valeant Pharmaceuticals
• Approval Status: Approved June 2011
• Indications:
 Partial-onset seizures
25

26. Retigabine: Mechanism of Action
Inhibitory synapse Excitatory synapse
Retigabine
26
Retigabine

27. Ezogabine = Retigabine (Potiga)
27

28. Rufinamide
• Company: Eisai Medical Research Inc.
• Approval Status: Approved November 2008
• Specific treatments:
 Lennox-Gastaut Syndrome
28

29. Rufinamide
29

30. Rufinamide: Mechanism of Action
Inhibitory synapse Excitatory synapse
Rufinamide
30

31. Rufinamide (Banzel)
31

32. Epilepsy’s new pipeline therapeutics
32
New Drugs
New route
(Enhanced Drug
Delivery)
Dietary Supplement
New Therapeutic
Devices
New in Egyptian Market
Marketed
Marketed
Marketed
Under Trial
Under Trial
Under Trial

33. Epilepsy’s new pipeline therapeutics
33
New Drugs
New route
(Enhanced Drug
Delivery)
Dietary Supplement
New Therapeutic
Devices
New in Egyptian Market
Marketed
Marketed
Marketed
Under Trial
Under Trial
Under Trial

34. Seletracetam(SEL)
34

35. Selurampanel
35
• 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

36. Bumetanide
36
NKCC1 inhibition
Neonatal seizures

37. Cannabidiol (Epidiolex)
37
March 14, 216 (GLOBE NEWSWIRE)
Dravet syndrome

38. 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.
Stiripentol (Diacomit)
38

39. Ganaxolone
39
PCDH 19 female pediatric
epilepsy

40. PCDH 19 female pediatric epilepsy
40
• 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.

41. IV Ganaxolone
April 15, 2016
41
Status epilepticus

42. Synthetic Huperzine A
• Company:Biscayne ph
• Derived from Chinese plant
Chinese club moss
• AchEI
• Phase II 2016 CPS
• Phase II 2017 Dravet syndrome
42

43. AED vs AEG
43
AED
VS
AEG
AEG
AED

45. Gene
expression
Signaling pathways
(ICER)
cAMP response
element
(CREB)
BDNF
JAK-STAT
REST
mTOR
Epigenetics
miRNA

46. Gene
expression
Signaling pathways
(ICER)
cAMP response
element
(CREB)
BDNF
JAK-STAT
REST
mTOR
Epigenetics
miRNA

51. AEG

52. Epilepsy’s new pipeline therapeutics
52
New Drugs
New route
(Enhanced Drug
Delivery)
Dietary Supplement
New Therapeutic
Devices
New in Egyptian Market
Marketed
Marketed
Marketed
Under Trial
Under Trial
Under Trial
52

53. Epilepsy’s new pipeline therapeutics
53
New Drugs
New route
(Enhanced Drug
Delivery)
Dietary Supplement
New Therapeutic
Devices
New in Egyptian Market
Marketed
Marketed
Marketed
Under Trial
Under Trial
Under Trial
53

54. 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

55. Intrabuccal midazolam (epistatus)
55

56. Diazepam rectal gel (Diastat)
56

57. Diazepam auto-injector

58. Diazepam auto-injector
58

59. Epilepsy’s new pipeline therapeutics
59
New Drugs
New route
(Enhanced Drug
Delivery)
Dietary Supplement
New Therapeutic
Devices
New in Egyptian Market
Marketed
Marketed
Marketed
Under Trial
Under Trial
Under Trial
59

60. Epilepsy’s new pipeline therapeutics
60
New Drugs
New route
(Enhanced Drug
Delivery)
Dietary Supplement
New Therapeutic
Devices
New in Egyptian Market
Marketed
Marketed
Marketed
Under Trial
Under Trial
Under Trial
60

61. Inhaled alprazolam
• Originator Alexza Pharmaceuticals
• Mechanism of Action GABA A receptor agonists
• Phase II
61

62. Staccato technology
62

63. Transdermal CBD gel ZYN002
63

64. Transdermal cannabidiol (CBD) gel
64

65. Intranasal midazolam
65

66. Intranasal Diazepam(Neurelis)
66

67. Epilepsy’s new pipeline therapeutics
67
New Drugs
New route
(Enhanced Drug
Delivery)
Dietary Supplement
New Therapeutic
Devices
New in Egyptian Market
Marketed
Marketed
Marketed
Under Trial
Under Trial
Under Trial
67

68. Epilepsy’s new pipeline therapeutics
68
New Drugs
New route
(Enhanced Drug
Delivery)
Dietary Supplement
New Therapeutic
Devices
New in Egyptian Market
Marketed
Marketed
Marketed
Under Trial
Under Trial
Under Trial
68

69. Triheptanoin in GLUT1 deficiency
•GDD
•Epilepsy
•Movement
disorders
69

70. Triheptanoin in GLUT1 deficiency
70

71. Epilepsy’s new pipeline therapeutics
71
New Drugs
New route
(Enhanced Drug
Delivery)
Dietary Supplement
New Therapeutic
Devices
New in Egyptian Market
Marketed
Marketed
Marketed
Under Trial
Under Trial
Under Trial
71

72. Epilepsy’s new pipeline therapeutics
72
New Drugs
New route
(Enhanced Drug
Delivery)
Dietary Supplement
New Therapeutic
Devices
New in Egyptian Market
Marketed
Marketed
Marketed
Under Trial
Under Trial
Under Trial
72

73. Responsive Neurostimulation
• FDA Approved
November 2013
• Adjunctive treatment
for adults with
medically refractory
partial seizures

74. Epilepsy Alarm Bed Seizure Detection

75. Anti-Suffocation Pillows

76. Watches

77. Epilepsy’s new pipeline therapeutics
77
New Drugs
New route
(Enhanced Drug
Delivery)
Dietary Supplement
New Therapeutic
Devices
New in Egyptian Market
Marketed
Marketed
Marketed
Under Trial
Under Trial
Under Trial
77

78. Epilepsy’s new pipeline therapeutics
78
New Drugs
New route
(Enhanced Drug
Delivery)
Dietary Supplement
New Therapeutic
Devices
New in Egyptian Market
Marketed
Marketed
Marketed
Under Trial
Under Trial
Under Trial
78

79. Trigeminal nerve stimulation (TNS)
79

80. Epilepsy’s new pipeline therapeutics
80
New Drugs
New route
(Enhanced Drug
Delivery)
Dietary Supplement
New Therapeutic
Devices
New in Egyptian Market
Marketed
Marketed
Marketed
Under Trial
Under Trial
Under Trial
80

81. Epilepsy’s new pipeline therapeutics
81
New Drugs
New route
(Enhanced Drug
Delivery)
Dietary Supplement
New Therapeutic
Devices
New in Egyptian Market
Marketed
Marketed
Marketed
Under Trial
Under Trial
Under Trial
81

82. Eslicarbazepine acetate
chemical structure

83. IV Lacosamide

84. IV Levetiracetam

85. Inhibitory synapse Excitatory synapse
Levetiracetam
85
Levetiracetam: Mechanism of action

86. Epilepsy’s new pipeline therapeutics
86
New Drugs
New route
(Enhanced Drug
Delivery)
Dietary Supplement
New Therapeutic
Devices
New in Egyptian Market
Marketed
Marketed
Marketed
Under Trial
Under Trial
Under Trial
86

87. Seizure control
Safety/tolerability
Compliance
ARS and SE
Detection and
Prediction of
seizures
New Devices
New drugs
OD dosing, XR formula
Rapid drug delivery
DO WE NEED MORE NEW EPILEPSY DRUGS?

88. 88
Overcoming challenges !!

89. THANK YOU
amrhasanneuro@kasralainy.edu.eg