Indication CINRYZE® (C1 esterase inhibitor [human]) is indicated for routine prophylaxis against angioedema attacks in adults, adolescents and pediatric patients (6 years of age and older) with Hereditary Angioedema (HAE).
CINRYZE has been proven to reduce the frequency, severity, duration of attacks, and the number of days of swelling of hereditary angioedema (HAE) attacks in adults and adolescents.1
Adults and adolescents: Primary endpoint analysis
The efficacy of CINRYZE in preventing HAE attacks in adult and adolescent patients was evaluated based on the number of HAE attacks during the 12-week treatment period with CINRYZE compared with the number of attacks during the 12-week placebo treatment period.1
CINRYZE significantly reduced the mean number of HAE attacks vs. placebo (p<0.0001). The number (standard deviation) of HAE attacks was 6.1 (5.4) while taking CINRYZE vs. 12.7 (4.8) on placebo.1
CINRYZE has been proven to reduce the frequency of HAE attacks.1
Primary efficacy outcome REDUCTION IN FREQUENCY OF ATTACKS
Mean number of HAE attacks over 12 weeks
15
10
5
0
Placebo12.7
CINRYZE6.1
(p<0.0001)
In 20 out of 22 patients taking CINRYZE, attack frequency was reduced.1
Prevention of HAE attacks : clinical trial results by subject1
Subject
Percent Reduction in Attack Frequency
1
100
2
100
3
100
4
100
5
90
6
88
7
84
8
83
9
78
10
76
11
60
Subject
Percent Reduction in Attack Frequency
12
47
13
43
14
43
15
32
16
31
17
25
18
21
19
10
20
1
21
-8
22
-85
The effectiveness of CINRYZE prophylaxis in reducing the number of HAE attacks was variable among the 22 subjects in a controlled clinical trial.1
20 patients experienced a reduction in attack frequency
Ranging from a 100% to 1% reduction in number of attacks
4 patients experienced no attacks during a 12-week period
2 patients experienced an increase in attack frequency
One patient showed an 8% increase in attacks
One patient showed an 85% increase in attacks
Study design
The pivotal trial was a randomized, double-blind, placebo-controlled, multicenter, crossover study of adults and adolescents designed to establish the safety (n=24) and efficacy (n=22) of CINRYZE prophylaxis in patients with a history of at least 2 HAE attacks per month. In addition to the primary efficacy analysis of attack frequency, secondary endpoints included the duration and severity of attacks and the number of days of swelling.1
Prevention with CINRYZE reduced the severity and duration of HAE attacks and days of swelling.1
Reduced attack severity REDUCTION IN MEAN SEVERITY OF ATTACKS
Mean severity of HAE attacks (Score from 1 to 3)
3.0
2.5
2.0
1.5
1.0
0.5
0
Placebo1.9
CINRYZE1.3
(p<0.01)
Severity: 1=Mild, 2=Moderate, 3=Severe
CINRYZE significantly reduced the mean severity of HAE attacks vs. placebo (p<0.01).
Mean severity of HAE attacks (SD): CINRYZE 1.3 (0.85) vs. placebo 1.9 (0.36)
Mean treatment effect (placebo minus CINRYZE) was 0.58 (95% CI, 0.19, 0.97)
Reduced attack duration REDUCTION IN MEAN DURATION OF ATTACKS
Mean duration of HAE attacks (Days)
5
4
3
2
1
0
Placebo3.4
CINRYZE2.1
(p<0.01)
CINRYZE significantly reduced the mean duration of HAE attacks vs. placebo (p<0.01).
Mean duration of HAE attacks in days (SD): CINRYZE 2.1 (1.13) vs. placebo 3.4 (1.4)
Mean treatment effect (placebo minus CINRYZE) was 1.23 (95% CI, 0.49, 1.96)
Reduced number of days of swelling REDUCTION IN DAYS OF SWELLING OVER 12 WEEKS
Mean number of days of swelling
35
30
25
20
15
10
5
0
Placebo29.6
CINRYZE10.1
CINRYZE significantly reduced the mean number of days of swelling vs. placebo (p<0.01).
Days of swelling (SD): CINRYZE 10.1 (10.73) vs. placebo 29.6 (16.9)
Mean treatment effect (placebo minus CINRYZE) was 19.5 (95% CI, 11.94, 27.06)