BACKUP SLIDES

1
BACK-UP SLIDES

• Presented during Cardiovascular and Renal Drugs
  Advisory Committee QA Sessions
• December 11, 2007

2
KYNAPID (vernakalant hydrochloride
injection)Cardiovascular and Renal
DrugsAdvisory Committee

• Astellas Pharma US, Inc.
• December 11, 2007

3
Subjects without AF Symptomsby Conversion
StatusPooled Primary Studies (3 Hours 7 Days)
EF 097
4
Treatment of Non-converters within First 24 h
Pooled Primary Studies (gt3h - 7d)
The majority of patients that remained in AF
after study treatment were treated with either
ECV or other antiarrhythmic agents within the
first 24 hours.
EF 096
5
Logistic Regression Analysis of Treatment-Induced
Conversion from Atrial Fibrillation to Sinus
Rhythm versus the Duration of Atrial Fibrillation
Figure 9 (page 55)
Full Analysis Set all randomized patients who
received any amount of study drug (ACT
I) Analysis based on treatment induced conversion
as determined by the CEC from Holter monitor or
12-lead ECG data if Holter results were missing
or not interpretable. (1) A logistic regression
model with AF duration (hours) as explanatory
variable. (2) Treatment-induced conversion from
AF to sinus rhythm as determined by the CEC from
results of the Holter monitor or 12-lead ECG data
if Holter results were missing or not
interpretable. (3) P-value from Wald chi-square
test (4) The extent to which the odds of
conversion decrease per day.
BB 028
6
Probability ofDetecting Infrequent Events
AE 175
7
Life-Table Estimate of the Maintenance of Sinus
Rhythm for Subjects Who Converted to Sinus Rhythm
within 90 Minutes (ACT II AF Patients)
Subject base full analysis set subjects who
converted within 90 minutes SR survival rate
SE standard error
EF 022
8
Maintenance of SR post Cardiac Surgery with
Ibutilide
VanderLugt JT, Mattioni T, Denker S, Torchiana D,
Ahern T, Wakefield LK, Perry KT, Kowey PR.
Efficacy and safety of ibutilide fumarate for the
conversion of atrial arrhythmias after cardiac
surgery. Circulation 1999 100 369-375
EF 035
9
ACT II Serious Adverse Events(0-24 Hours)
Source ACT II study report Table 14.3.4.2.1
AE 011
10
Prevalence and Timing of Bradycardia/Sinus
Bradycardia AEs Occurring in First 24 HoursAll
Patients
Infusion
Infusion
AE 015
11
Baseline Characteristics by Ejection FractionAll
Phase 3 with EF collected
AE 036
SCS Amendment Table 4.7
12
Treatment-Induced Conversion of AF to Sinus
Rhythm within 90 Minutes(Short-Duration AF)ACT I
EF 098
13
Treatment-Induced Conversion of AF to Sinus
Rhythm within 90 Minutes(Short-Duration AF)ACT
III
EF 099
14
Cumulative Benefit (gt3h-7d)Pooled Primary
Population
EF 100
15
Safety EventsAll Patients
EF 101
16
Safety EventsAll Patients
EF 102
17
Randomized but Did Not Receive Study DrugPooled
Primary (ACT I and III) Studies

• 31 patients randomized but not dosed
• 4.4 Placebo Group (11/247)
• Conversion to SR 2.8 (7/247)
• Did not meet I/E Criteria 1.6 (4/247)
• 5.6 Vernakalant Group (20/359)
• Conversion to SR 3.3 (12/359)
• Did not meet I/E criteria 1.7 (6/359)
• Drug not available 0.3 (1/359)
• Not specified 0.3 (1/359)

AE 173
18
Peri-infusional Hypotension AEsAll Patients
Infusion
Infusion
AE 016
19
Bradycardia and ConversionBetween 0-2 Hours
Post-DoseAll Phase 3 Studies
AE 153
10/2/2009 1051 PM
20
Bradycardia and Electrical CardioversionBetween
2-24 Hours Post-DoseAll Phase 3 Studies
AE 154
10/2/2009 1051 PM