Download pdf - Epilepsy Treatment Update for Patients Suffering from ... · Epilepsy Treatment Update for Patients Suffering From Seizure Clusters Tuesday, December 3, 2019 National Harbor, MD US-P-NZ-SC-1900152

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 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 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



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




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.



Important Safety Information (cont’d)



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.






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.






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



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

=



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



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



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



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



in 122/175a patients

treated with NAYZILAM

70%

Overall Treatment Success2

Second dose (open label)2,3

5 mg NAYZILAM

55%

66%

54%


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



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



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



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



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.


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



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




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


Prior to treatment, the healthcare professional should instruct the individual administering on how to identify seizure

clusters and use the product appropriately



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!