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TRANSCRIPT
Epilepsy Treatment Update
for Patients Suffering
From Seizure Clusters
Tuesday, December 3, 2019
National Harbor, MD
US-P-NZ-SC-1900152 12/19
• The speaker today is being compensated by UCB, the sponsor of this presentation
• The use of products in any way other than that specified by the FDA approved US Prescribing
Information is off-label and cannot be recommended by UCB
• Disclosures: research grants from Lundbeck, Eisai; advisory boards and consulting for Abbot,
Alliance, Aquestive, Eisai, Lundbeck, SK Life Sciences, UCB Pharma; speaker bureau for
Aquestive, Eisai, Sunovion, UCB Pharma
Disclaimer!
2
• Seizure clusters can be broadly
defined as acute episodes of
consecutive seizures that occur with
short interictal periods and may be
distinguishable from a patient’s typical
seizure pattern or frequency1-4
• No consensus definition of seizure
clusters currently exists1
5
What Is a Seizure Cluster?
FlurriesAcute
Repetitive Seizures
Serial Seizures
Crescendo Seizures
Cyclical Seizures
Recurrent Seizures
Various Alternative Names for Seizure Clusters5
Sources: 1. Haut SR. Curr Opin Neurol. 2015;28:143-150. 2. Mitchell WG. Epilepsia. 2996;37:S74-S80. 3. Haut SR. Epilepsy Behav. 2006;8:50-55. 4. Dreifuss FE, et al. N Engl J Med. 1998;338:1869-1875.
5. Jafarpour S, et al. Seizure. 2019;68:9-15.
6
Burden of Seizure Clusters
10%55%
48%
34%
52%
41%
Driving
Overall mood
Work
Independence
Travel
Extracurricularactivities
Impact of Seizure Clusters on Patients’ and Their Caregivers’ Lives
Percent of Respondents, %
Patients (N=259) Caregivers (N=263)
Source: Penovich PE, et al. Neurologist. 2017;22:207-214.
Seizure clusters represent substantial burdens to patients’ their caregivers’ lives
69%
69%
69%
67%
59%
58%
Driving
Overall mood
Work
Independence
Travel
Extracurricularactivities
7
Gaps in Communication About Seizure Clusters
Healthcare Professional Community Member
Time frame• 12-hour period for children
• 24-hour period for adults
• Can range from daily to once a year
Duration• Over a relatively short period of time, usually
less than 24 hours• Ranges from a few days to a few weeks
Frequency • Multiple seizures, usually 3 or more • No specific number of seizures
Note: Based on qualitative reviews and analyses of the medical literature (Healthcare Professional) and of the Epilepsy Foundation
website (Community Member). This theme refers to the understanding or the definition of seizure clusters as understood by healthcare professionals
or epilepsy community members.
Source: Buelow JM, et al. Epilepsy Behav. 2016;57:16-22.
8
Average Seizure Cluster Duration
Compared With Isolated Seizures
Seizure Cluster
Definition
Mean Number of
Seizures/Cluster
Mean (SD) Seizure Duration, Seconds Intracluster vs Terminal
Seizure Duration
P ValuebIntracluster
Seizures
Terminal
Seizures
Isolated
Seizures
2 or more seizures
within 2 hours2.8 71 (78) 84 (68) 90 (92) 0.014
2 or more seizures
within 4 hours3.2 78 (72) 95 (98) 86 (92) 0.011
2 or more seizures
within 8 hours3.8 82 (81) 83 (69) 91 (108) 0.294
Seizure Duration Based on Position Within a Cluster Compared With Isolated (Non-Cluster) Seizuresa
a Data based on EEG findings from 996 seizures among 92 patients.b There were no statistically significant differences between mean terminal seizure duration and mean isolated seizure duration.
Abbreviations: EEG, electroencephalogram.
Source: Ferastraoaru V, et al. Epilepsia. 2016;57:889-895.
9
Seizure Clusters May Involve the Failure of
Inhibitory Mechanisms
Single Neurons
Transmembrane ion gradients
Energy failure (eg, ATP or glucose loss)
Local Network of Neurons
Gap junction decoupling
Changes in neuromodulator levels
GABAergic synaptic inhibition
Remote Brain Regions
GABAergic synaptic inhibition
Substantia nigra pars reticulataSeizure onset zone
Mechanisms Reported to Be Involved in Seizure Termination1
Binding of benzodiazepines to the GABA receptor is believed to potentiate GABAergic inhibition2
Abbreviations: ATP, adenosine triphosphate; GABA, γ-aminobutyric acid.
Sources: 1. Lado FA, Moshé SL. Epilepsia. 2008;49:1651-1664. 2. Riss J, et al. Acta Neurol Scand. 2008;118:69-86.
10
Seizure Clusters and Hospitalizations
Abbreviation: SE, status epilepticus.
Source: Haut SR, et al. Epilepsia. 2005;46:146-149.
73%
59%
0% 25% 50% 75% 100%
Seizure clustering(N=41)
Nonclustering(N=100)
Patients, %
Seizure-Related Hospitalizations Among Patients With Epilepsy (non-SE)
P=0.006
Note: Seizure cluster defined as 3 or more seizures in 24-hour period.
11
Seizure Clusters and Status Epilepticus
Sources: 1. Haut SR, et al. Epilepsia. 2005;46:146-149. 2. Haut SR, et al. Epilepsia. 1999;40:1832-1834.
39%44%
12% 13%
0%
25%
50%
75%
100%
Haut SR, et al (2005) Haut SR, et al (1999)
Pa
tie
nts
, %
Seizure clustering Nonclustering
History of Convulsive Status Epilepticus Among Patients
With and Without Seizure Clusters
16/41 12/100
P=0.03
16/36 5/40
P <0.002
1 2
Note: Seizure clusters defined as 3 or more seizures over 24-hour period in both studies.
12
Seizure Clusters and Mortality
Patients with seizure clusters have a
~3.5-fold greater risk of death*
compared to patients without clusters
*95% CI, 1.25-9.78
Abbreviation: CI, confidence interval.
Source: Sillanpää M, Schmidt D. Brain. 2008;131:938-944.
Cu
mu
lative
Pro
po
rtio
n S
urv
ivin
g,
%
Years After Onset of Epilepsy
Survival With and Without Seizure Clusters
100 –
90 –
80 –
70 –
60 –
50 –
40 –
30 –
20 –
10 –
0 –
0 5 10 15 20 25 30 35 40 45
No Seizure Clusters (N=94)
Seizure Clusters During Treatment (N=12)
13
2.3%
4.7%
7.8%
8.7%
10.5%
10.5%
15.4%
51.0%
70.6%
0% 25% 50% 75% 100%
Lennox-Gastaut Syndrome
Psychogenic nonepileptic seizure
Drop seizure
Tonic seizure
Nocturnal seizure
Febrile seizures
Status epilepticus
Simple partial seizure
Complex partial seizure
Patients with clusters (N=612)Patients without clusters (N=3504)
Prevalence of Select Risk Factors Among Patients Aged 16 Years or Older With and Without Seizure Clusters
Patients With Risk Factor, %Risk Factor
History of…
Note: All P values <0.05 based on a univariate analysis.
Source: Chen B, et al. Epilepsy Res. 2017;133:98-102.
Risk Factors for Experiencing Seizure Clusters
Seizure clusters are associated with multiple seizure types
48.5%
43.4%
5.8%
7.9%
7.1%
2.0%
1.9%
2.5%
0.9%
Note: Data from a retrospective univariate analysis.
14
Seizure Emergency Action Plans
30%
Have a seizure
emergency plan
In a survey of 259 patients with epilepsy…
20%
20%
24%
34%
11%
10%
7%
5%
27%
79%
67%
61%
50%
28%
21%
12%
2%
1%
-100% -50% 0% 50% 100%
Patient
Physician
Rescue medication
Call doctor's office
Visit ER
Stay calm
Extra/increased dose of AED
VNS
Visit urgent care
Other
Typically nothing
Clinician Recommendations and Patient
Responses to Seizure Clusters
Patients (N=259), % Clinicians (N=339), %
Most patients with seizure clusters report that they do not have a seizure emergency plan
Abbreviations: AED, antiepileptic drug; ER, emergency room, VNS, vagus nerve stimulator.
Source: Penovich PE, et al. Neurologist. 2017;22:207-214.
70%
Do not have a
seizure emergency plan Patients
Clinicians
15
Use of Various Benzodiazepines
as Rescue Medication
28.9%
7.8% 7.0% 6.9%5.4%
0%
10%
20%
30%
40%
Lorazepam(oral)
Diazepam(rectal)
Diazepam(oral)
Midazolam(intranasal)
Clonazepam(oral)
Pa
tie
nts
, %
Rescue Medication Use for Patients With Seizure Clusters (N=612)
n=177 n=48 n=43 n=42 n=33
Less than half (43.5%) of patients who experienced seizure clusters had a prescription for a rescue medication
Source: Chen B, et al. Epilepsy Res. 2017;133:98-102.
56.5%
No prescription
30.6%
1 prescription
10.8%
2 prescriptions
2.1%
3+ prescriptions
Prescriptions for Rescue Medications Among
Patients With Seizure Clusters (N=612)
16
Pharmacokinetics of Benzodiazepines
0 1 2 3 4 5 6 7 8 9 10 11 12
Clorazepate (IM)
Clorazepate (PO)
Clonazepam (PO)
Clobazam (PO)
Diazepam (PO)
Diazepam (IM)
Diazepam (R)
Midazolam (PO)
Midazolam (IM)
Midazolam (IN)
Lorazepam (PO)
Lorazepam (SL)
Lorazepam (IM)
Tmax (hours)
2.7-11b
0.5-2b
1-4
1.3-1.7
0.5-1.5
0.5-1.0
0.17-0.75
0.5-0.97
0.24-0.51
2.4
2.3
1.2
Abbreviations: IM, intramuscular; IN, intranasal; PO, oral; R, rectal; SL, sublingual.
Sources: 1. Riss J, et al. Acta Neurol Scand. 2008;118:69-86. 2. Knoester PD, et al. Br J Clin Pharmacol. 2002;53:501-507.
0.15-0.32
a In healthy subjects.b Tmax for N-desmethyldiazepam after administration of clorazepate.c Compounded intranasal midazolam.2
Elimination Half-lifea (hours)
>24
19-60
21-70
1-4
7-26
10-30
c
17
NAYZILAM® (midazolam) nasal spray, CIV
Product Overview
Please see Important Safety Information, including the Boxed Warning for concomitant use with opioids, included
in this presentation.
Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com
NAYZILAM® is a registered trademark of the UCB Group of Companies.
All other trademarks are the property of their respective owners.
©2019 UCB, Inc., Smyrna, GA 30080. All rights reserved.
US-P-NZ-SC-1900152 12/19
18
NAYZILAM® Is the First and Only Nasal Spray
Indicated to Treat Seizure Clusters
NAYZILAM is a benzodiazepine indicated for the acute treatment of intermittent, stereotypic episodes of frequent
seizure activity (ie, seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in
patients with epilepsy 12 years of age and older.
WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS
Concomitant use of benzodiazepines and opioids may result in
profound sedation, respiratory depression, coma, and death
[see Warnings and Precautions (5.1), Drug Interactions (7.2)].
Reserve concomitant prescribing of these drugs for use in patients
for whom alternative treatment options are inadequate.
Limit dosages and durations to the minimum required.
Follow patients for signs and symptoms of respiratory depression
and sedation.
Please see additional Important Safety Information within this presentation.
Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com.Source: NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc.
19
NAYZILAM® Is Now Available
Source: NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc.
Image is for illustrative
purposes only.
Single-use nasal spray supplied in
boxes of 2 blister pack units
NAYZILAM can be administered
by a non–healthcare professional
NAYZILAM is a midazolam formulation
designed for nasal delivery
Please see additional Important Safety Information within this presentation.
Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com.
NAYZILAM is contraindicated in patients with acute narrow-angle glaucoma. Concomitant use
of benzodiazepines, including NAYZILAM, and opioids may result in profound sedation,
respiratory depression, coma, and death. NAYZILAM may cause increased CNS-depressant
effect when used with alcohol or other CNS depressants. Concomitant use with moderate or
strong CYP3A4 inhibitors may result in prolonged sedation due to a decrease in plasma
clearance of midazolam. Antiepileptic drugs, including NAYZILAM, increase the risk of suicidal
ideation and behavior. Midazolam is associated with a high incidence of partial or complete
impairment of recall for the next several hours.
Please see additional Important Safety Information within this presentation.
Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com. 20
NAYZILAM Pharmacokinetics
aMean plasma concentration was estimated from the Pharmacokinetic Analysis Population: All subjects who received both test doses in the ARTEMIS I clinical trial, with
sufficient plasma concentration data to accurately estimate pharmacokinetic parameters (n=235).2
bThe formulation of intranasal midazolam used in this study was different from the final formulation of NAYZILAM.Sources: 1. NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc. 2. Data on file. UCB Inc.
Hours Post Dose
Me
an
(±S
D)
NA
YZ
ILA
M P
lasm
a
Co
nce
ntr
ation
(n
g/m
L)
Absorption
• Median Tmax 17.3 minutes
• Mean absolute bioavailability ~44%
Distribution
• Total volume of distribution ~226.5 L
• ~97% protein bound
Metabolism
• Primarily liver and intestinal CYP3A4
Elimination
• Half-life 2.1 hours to 6.2 hours
Mean Plasma Concentration After 2 Doses of Intranasal Midazolam
Administered 10 Minutes Apart in Patients With Epilepsy2,a,b
Detected in plasma by 5 minutes post dose
Key Pharmacokinetic Parameters
in Healthy Adults1
Please see additional Important Safety Information within this presentation.
Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com. 21
CONTRAINDICATIONS
NAYZILAM is contraindicated in patients with acute narrow-angle glaucoma.
RISKS FROM CONCOMITANT USE WITH OPIOIDS
Concomitant use of benzodiazepines, including NAYZILAM, and opioids may result in profound sedation,
respiratory depression, coma, and death.
• Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment
options are inadequate.
• Limit dosages and durations to the minimum required.
• Follow patients for signs and symptoms of respiratory depression and sedation.
RISKS OF CARDIORESPIRATORY ADVERSE REACTIONS
Serious cardiorespiratory adverse reactions have occurred after administration of midazolam. Warn patients and
caregivers about the risks of respiratory depression, cardiac, and respiratory arrest.
Respiratory depression was observed with the administration of NAYZILAM during clinical trials. Cardiac or respiratory
arrest caused by NAYZILAM was not reported during clinical trials.
NAYZILAM® (midazolam) Nasal Spray, CIV
Important Safety Information
Source: NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc.
Please see additional Important Safety Information within this presentation.
Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com. 22
CENTRAL NERVOUS SYSTEM DEPRESSION FROM CONCOMITANT USE WITH OTHER CENTRAL NERVOUS
SYSTEM DEPRESSANTS, OR MODERATE OR STRONG CYP3A4 INHIBITORS
Drug products containing midazolam, including NAYZILAM, have a central nervous system (CNS) depressant effect.
Risks from Concomitant Use with Other CNS Depressants
NAYZILAM may cause an increased CNS-depressant effect when used with alcohol or other CNS depressants
(eg, opioids). Warn patients and caregivers that the use of NAYZILAM in combination with alcohol or other CNS
depressant drugs may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may
contribute to profound and/or prolonged drug effect.
Risks from Concomitant Use with Moderate or Strong CYP3A4 Inhibitors
Concomitant use of NAYZILAM with moderate or strong CYP3A4 enzyme inhibitors may result in prolonged sedation
because of a decrease in plasma clearance of midazolam. Caution patients against engaging in hazardous
occupations requiring mental alertness, such as operating machinery, driving a motor vehicle or riding a bicycle until
they have completely returned to their level of baseline functioning.
Source: NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc.
NAYZILAM® (midazolam) Nasal Spray, CIV
Important Safety Information (cont’d)
Please see additional Important Safety Information within this presentation.
Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com. 23
SUICIDAL BEHAVIOR AND IDEATION
Antiepileptic drugs (AEDs), including NAYZILAM, increase the risk of suicidal thoughts or behavior in patients taking
these drugs for any indication. Monitor patients treated with NAYZILAM for the emergence or worsening of
depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Advise patients and
caregivers to be alert for these behavioral changes and to immediately report them to the healthcare provider.
IMPAIRED COGNITIVE FUNCTION
Midazolam, including NAYZILAM, is associated with a high incidence of partial or complete impairment of recall for
several hours following an administered dose. Counsel patients on when they can engage in activities requiring
complete mental alertness, operate hazardous machinery, or drive a motor vehicle after taking NAYZILAM.
GLAUCOMA
Benzodiazepines, including NAYZILAM, can increase intraocular pressure in patients with glaucoma. NAYZILAM may
be used in patients with open-angle glaucoma only if they are receiving appropriate therapy. NAYZILAM is
contraindicated in patients with narrow-angle glaucoma.
Source: NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc.
NAYZILAM® (midazolam) Nasal Spray, CIV
Important Safety Information (cont’d)
Please see additional Important Safety Information within this presentation.
Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com. 24
ADVERSE REACTIONS
In the randomized, double-blind, placebo-controlled trial, the most common adverse reactions (≥5% in any NAYZILAM
treatment group) were somnolence, headache, nasal discomfort, throat irritation, and rhinorrhea.
NAYZILAM is a Schedule IV controlled substance.
Source: NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc.
NAYZILAM® (midazolam) Nasal Spray, CIV
Important Safety Information (cont’d)
Please see additional Important Safety Information within this presentation.
Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com. 25
ARTEMIS I: NAYZILAM for the Acute Treatment
of Seizure Clusters in Patients ≥12 Years of Age1,2
aThe patient did not have <8 breaths per minute, require emergency rescue treatment and assisted breathing or intubation, or have excessive sedation.1
Sources: 1. Detyniecki K, et al. Epilepsia. 2019;60:1797-1808. 2. NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc.
5 mg NAYZILAM
(double-blind)
n=134
Placebo
(double-blind)
n=67
Treatment
Groups
Randomized 2:1
1st
Dose
5 mg NAYZILAM
(open-label)
2nd
Dose
ARTEMIS I Study Design: Comparative Phase1,2
If seizure cluster did not
stop within 10 minutes
Or another seizure
occurred within 6 hours
And no sign of
respiratory depressiona
• Tolerability was assessed in the Test Phase in which 292 patients received two 5 mg doses of NAYZILAM separated by 10 minutes
in the absence of a seizure: patients who met predefined criteria continued on to the Comparative Phase2
Please see additional Important Safety Information within this presentation.
Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com. 26
ARTEMIS I Efficacy Endpoints
aReturn to baseline functionality: time when subject was able to return to what he/she was doing prior to the seizure cluster.2
Sources: 1. Detyniecki K, et al. Epilepsia. 2019;60:1797-1808. 2. Data on File. UCB Inc.
Treatment success with second dose
(open‐label)
Time to next seizure occurring
>10 minutes after drug administration
Return to baseline functionality within
24 hours of drug administrationa
+
Primary Endpoint1
Treatment
Success
No recurrence of seizures
within 6 hours of initial
blinded study drug dose
Seizure termination within
10 minutes after initial
blinded study drug dose
Key Secondary and Exploratory Endpoints1
=
Please see additional Important Safety Information within this presentation.
Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com. 27
ARTEMIS I Baseline Characteristics
and Inclusion Criteria
aClusters had to be composed of ≥2 seizures (focal or generalized); last ≥10 minutes; and have an observable, stereotyped, and recognizably different pattern from patients’
noncluster seizure activity, with another seizure occurring within 6 hours of cluster onset.Abbreviation: AEDs, antiepileptic drugs.
Sources: 1. Detyniecki K, et al. Epilepsia. 2019;60:1797-1808. 2. NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc. 3. Data on File. UCB Inc.
Age (years)1,2
Mean: 33
Range: 12-62
≥12 to <18 years: 10 (5%)
≥18 to <65 years: 191 (95%)
Sex1,2
Female: 103 (51%)
Number of AEDs3
<2 seizure medications: 47 (23.4%)
≥2 to <4 seizure medications: 85 (42.3%)
≥4 seizure medications: 69 (34.3%)
Safety Population: N=292
Randomized Safety Population: N=201
Patient Population Size1
Select Inclusion Criteria1
• Aged ≥12 years
• Established diagnosis of epilepsy
• On stable regimen of antiepileptic drugs
• Adult caregiver able to recognize clusters
and administer treatment
• Documented history of seizure clusters
(>3 months before visit 1)a
Please see additional Important Safety Information within this presentation.
Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com. 28
ARTEMIS I Baseline Characteristics:
Seizure Cluster History
Abbreviation: GTC, generalized tonic-clonic.
Source: Detyniecki K, et al. Epilepsia. 2019;60:1797-1808.
0 20 40 60 80 100
Other
Atonic
Myoclonic
Absence
Tonic
Primary GTC
Simple partial
Secondarygeneralized
Complex partial
Cluster Seizure Typesa
NAYZILAM 5 mg (n=134)
Placebo (n=67)
Percent of Patients, %
NAYZILAM® Placebo
Typical cluster duration (min) n=129 n=63
Median
Range
65.00
2.5-4320.0
60.00
8.5-2880.0
Seizures per cluster episode n=134 n=67
Median
Range
5.2
2-200
6.0
2-170
Episodes in year before visit n=134 n=67
Median
Range
18
3-999
15
4-600
Years since clusters onset n=133 n=63
Median
Range
5.0
0.3-48.0
5.0
0.5-32.0
Seizure Characteristics
aPatients may have reported >1 seizure type.
Patients enrolled in ARTEMIS I had several different seizure types, with a median cluster duration of 65 minutes
Please see additional Important Safety Information within this presentation.
Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com. 29
81%
58%54%
70%
37%34%
0
10
20
30
40
50
60
70
80
90
100
Pe
rce
nt o
f P
atie
nts
Seizure Termination
<10 min
No Recurrence
10 min–6 h
Treatment
Success
NAYZILAM 5 mg
Placebo
Treatment Response With a Single Dose of NAYZILAM®1,2
P=0.011P=0.007
More Than 50% of Patients Achieved
Treatment Success With a Single Dose1
Sources: 1. NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc. 2. Data on file. UCB Inc.
n=108 n=47 n=78 n=25 n=72 n=23
P=0.110
In the randomized, double-blind, placebo-controlled trial, the most common adverse reactions (≥5% in any NAYZILAM treatment group)
were somnolence, headache, nasal discomfort, throat irritation, and rhinorrhea.1
Please see additional Important Safety Information within this presentation.
Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com. 30
70% of Patients Achieved Treatment Success
With Any Dose2
First Dose (blind)1,2
5 mg NAYZILAM
First dose (blind)1,2
Placebo
Randomized
Treatment
Groups
aOne hundred seventy-five patients were treated with NAYZILAM: 134 patients in the NAYZILAM arm and 41 patients in the placebo arm.2
Sources: 1. NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc. 2. Data on file. UCB Inc. 3. Detyniecki K, et al. Epilepsia. 2019;60:1797-1808.
Second dose (open label)2,3
5 mg NAYZILAM
Treatment Successn=72/134
Treatment Successn=23/42
Treatment Successn=27/41
in 122/175a patients
treated with NAYZILAM
70%
Overall Treatment Success2
Second dose (open label)2,3
5 mg NAYZILAM
55%
66%
54%
Treatment Successn=23/67
34%
Respiratory depression was observed with the administration of NAYZILAM during clinical trials. Cardiac or respiratory
arrest caused by NAYZILAM was not reported during clinical trials.1
Please see additional Important Safety Information within this presentation.
Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com. 31
NAYZILAM-treated Patients Had a Greater Probability
of No Seizure Recurrence for 24 Hours Post-doseProbability of Experiencing No Seizures Over the 24‐hour Observation Period
Beginning 10 Minutes After Drug Administration1,2
NAYZILAM: 58%
Placebo: 37%
aPatients who did not have another seizure before the end of the 24‐hour observation period, and who had not been administered the second dose of trial drug, were
censored at the end of the observation period. Those administered the second dose of trial drug who did not have a seizure before the administration of the second
dose were censored at the time of the second dose.2
Sources: 1. NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc. 2. Detyniecki K, et al. Epilepsia. 2019;60:1797-1808.
Pro
ba
bili
ty o
f n
o S
eiz
ure
s
Time After Administration of Double-Blind Trial Drug (Hours)
NAYZILAM
Censored NAYZILAMa
Placebo
Censored Placeboa
21% difference
P=0.0124
Antiepileptic drugs (AEDs), including NAYZILAM, increase the risk of suicidal thoughts or behavior in patients taking these drugs
for any indication.1
Please see additional Important Safety Information within this presentation.
Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com. 32
With NAYZILAM®, More Patients Returned to Baseline
Functionality Within 24 Hours vs Placebo
aReturn to baseline functionality: time when subject was able to return to what he/she was doing prior to the seizure cluster.1
Abbreviation: AEs, adverse events.
Sources: 1. Detyniecki K, et al. Epilepsia. 2019;60:1797-1808. 2. Data on file. UCB Inc. 3. NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc.
72.4
43.3
0
10
20
30
40
50
60
70
80
90
100
NAYZILAM Placebo
Return to Baseline Functionality Within 24 Hours1P
erc
en
t o
f P
ati
en
ts, %
29.1% difference
P<0.0001
Median Time to Return to Full
Baseline Functionality2,a
• Return to baseline comparable to placebo
(1.4 hours NAYZILAM vs 1.3 hours placebo)2
Midazolam, including NAYZILAM, is associated with a high incidence of partial or complete impairment of recall for several hours following an
administered dose.3
Respiratory depression was observed with the administration of NAYZILAM during clinical trials. Cardiac or respiratory arrest caused
by NAYZILAM was not reported during clinical trials.3
Please see additional Important Safety Information within this presentation.
Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com. 33
NAYZILAM® Adverse Event Profile (≥ 2% of NAYZILAM
Patients and Greater Than Placebo)
aAdverse reactions that occurred within 2 days after NAYZILAM administration are included. bPatients were permitted to take a second, open-label dose of NAYZILAM 5 mg
between 10 minutes and 6 hours following the initial blinded dose of NAYZILAM 5 mg or placebo if they experienced seizure recurrence or an incomplete resolution of the
episode. The Placebo + NAYZILAM 5 mg and NAYZILAM 5 mg + 5 mg columns represent patients who received a second dose of NAYZILAM 5 mg after receiving a
blinded initial dose of placebo or NAYZILAM 5 mg.TEAE, treatment‐emergent adverse event.
Sources: 1. NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc. 2. Detyniecki K, et al. Epilepsia. 2019;60:1797-1808.
• The most common adverse
reactions (≥5% in any NAYZILAM
treatment group) were somnolence,
headache, nasal discomfort, throat
irritation, and rhinorrhea1
• Most adverse reactions were mild
or moderate in intensity2
• At least one adverse event related
to acute central respiratory
depression was reported
in 10 (3.4%) patients2
• NAYZILAM was well tolerated.
• No patients discontinued during
the comparative phase
of the Phase 3 study of NAYZILAM2
Body System/
Adverse ReactionaPlacebo
NAYZILAMb
NAYZILAM
5 mg
Placebo +
NAYZILAM 5
mg
NAYZILAM
5 mg + 5 mg
Any NAYZILAM
Treatment
Group
N=26
%
N=91
%
N=41
%
N=43
%
N=175
%
Nervous System
Somnolence 4 10 10 9 10
Headache 0 7 0 2 4
Dysarthria 0 2 2 2 2
Application Site
Nasal Discomfort 8 5 7 16 9
Throat Irritation 0 2 2 7 3
Rhinorrhea 0 3 0 5 3
Product Taste Abnormal 0 4 0 0 2
Eye Disorders
Lacrimation Increased 0 1 2 2 2
Please see additional Important Safety Information within this presentation.
Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com. 34
NAYZILAM® Dosing
aIf the patient has not responded to the initial dose. Do not administer if the patient has trouble breathing or if there is excessive sedation uncharacteristic of the patient
during a seizure cluster episode.
Source: NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc.
Do not use more than 2 doses
of NAYZILAM to treat a single episode
Treat no more than 1 episode every
3 days or 5 episodes per month
Administer one spray (5 mg)
into one nostril
Administer one spray (5 mg) into
opposite nostril after 10 minutesa
1st Dose
2nd Dose
(if needed)
DosingMaximum Dosage &
Treatment Frequency
Image is for illustrative
purposes only.
• For patients at increased risk of respiratory depression from benzodiazepines, administration under healthcare professional
supervision should be considered prior to treatment; this administration may be performed in the absence of a seizure episode.1
• Benzodiazepines, including NAYZILAM, can increase intraocular pressure in patients with glaucoma. NAYZILAM may be used in
patients with open-angle glaucoma only if they are receiving appropriate therapy. NAYZILAM is contraindicated in patients with
narrow-angle glaucoma.1
• Concomitant use of NAYZILAM with moderate or strong CYP3A4 enzyme inhibitors may result in prolonged sedation.1
Please see additional Important Safety Information within this presentation.
Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com. 35
NAYZILAM® Treats Seizure Clusters
in the Outpatient Setting
• Can be administered by any non–healthcare professional
• No priming or assembly necessary
• Can be administered in an outpatient setting
• May be administered to a patient during or after a seizure within a cluster
• Requires no active inhalation; patient may be unconscious
Source: NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc.
Please see additional Important Safety Information within this presentation.
Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com. 36
Please see the full instructions for use in the Prescribing Information and discuss with the patient and their caregiver.
Administering NAYZILAM®
Hold the nasal spray unit with
your thumb on the plunger and
your middle and index fingers on
each side of the nozzle.
Do not press the plunger yet.
Place the tip of the nozzle into
one nostril until your fingers are
against the bottom of the
patient’s nose.
Press the plunger firmly.
1. HOLD 2. PLACE 3. PRESS
Source: NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc.
Prior to treatment, the healthcare professional should instruct the individual administering on how to identify seizure
clusters and use the product appropriately
Please see additional Important Safety Information within this presentation.
Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com. 37
NAYZILAM® for the Treatment of Seizure Clusters
aBaseline duration of seizure clusters in NAYZILAM arm was a median of 65 minutes (2.5-4320.0 minutes).3 bPrimary endpoint of treatment success included 2 components: the
termination of seizures within 10 minutes after the double-blind (first) dose and no recurrence of seizures between 10 minutes and 6 hours (double-blind observation period).1
CExploratory endpoint: time to return to full baseline functionality as determined by the caregiver.3 dRange: 1.1-2.0 hours.2
Sources: 1. NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc. 2. Data on file. UCB Inc. 3. Detyniecki K, et al. Epilepsia. 2019;60:1797-1808.
10 MINUTES TO STOP SEIZURE CLUSTERS1
• In 81% of patients, NAYZILAM terminated seizure cluster activity
within 10 minutesa,b
No seizure recurrence for up to 6 hours1
• 58% of patients had no seizure recurrence between
10 minutes and up to 6 hours after drug administrationa
Treatment Success
• First dose 54%1
• All doses 70%2
• Serious cardiorespiratory adverse reactions have occurred after
administration of midazolam. Warn patients and caregivers about
the risks of respiratory depression, cardiac and respiratory arrest.1
• Respiratory depression was observed with the administration of
NAYZILAM during clinical trials. Cardiac or respiratory arrest
caused by NAYZILAM was not reported during clinical trials.1
90 MINUTES TO GET PATIENTS BACK TO BASELINE FUNCTION2
• For all seizure clusters treated with NAYZILAM,
the median time to return to full baseline functionalityc after trial drug
administration was ~90 minutes2,d
• Midazolam, including NAYZILAM, is associated with a high incidence
of partial or complete impairment of recall for several hours following
an administered dose.1
24 HOURS OF NO SEIZURE RECURRENCE
IN MAJORITY OF PATIENTS1
• Treatment with NAYZILAM significantly prolonged the time
to the next seizure within 24 hours after double-blind study drug
administration compared with placebo (P=0.012).3
• In the randomized, double-blind, placebo-controlled trial,
the most common adverse reactions (≥5% in any NAYZILAM
treatment group) were somnolence, headache, nasal discomfort,
throat irritation, and rhinorrhea.1
Important Safety Information1
RISKS FROM CONCOMITANT USE WITH OPIOIDS
Concomitant use of benzodiazepines, including NAYZILAM, and opioids may result in profound sedation, respiratory depression, coma, and death.
• Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
• Limit dosages and durations to the minimum required.
• Follow patients for signs and symptoms of respiratory depression and sedation.
Thank you!