What is CINRYZE?

Not real patients

Efficacy of CINRYZE

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. In pediatric patients (age 7 to 11), CINRYZE was shown to reduce the number of HAE attacks, lessen the severity of attacks, and reduce the use of acute treatment compared to baseline.

CINRYZE in pediatric patients—shown to reduce the frequency of HAE attacks in children as young as 6

Reduction in frequency of attacks in pediactric patients

Time-nomoralized mean number
of HAE attacks per month
4
3.5
3
2.5
2
1.5
1
.5
0
Observation
Period
3.7
CINRYZE
500 U
1.2
CINRYZE
1,000 U
0.7

  • CINRYZE demonstrated a reduction in the number HAE attacks from baseline
    • 71.1% and 84.5% mean reduction in attacks (500 U and 1,000 U, respectively)
  • Mean absolute reduction in number of attacks: -2.6 (500 U), -3.0 (1,000 U)

Study design:

A randomized, single-blind, multi-center, dose-ranging cross-over study in 12 pediatric patients with HAE (7 to 11 years old). After an observation period of 12 weeks, patients were randomized to receive either CINRYZE 500 U or CINRYZE 1,000 U every 3 to 4 days for 12 weeks. Patients were then crossed-over to the alternative dose for an additional 12-week period. Efficacy endpoints which were met included reduction in the number of attacks, along with lessened severity of attacks and reduction in the use of acute treatment compared with baseline.

Adult and adolescent patients: 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.

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.

CINRYZE has been proven to reduce the frequency of HAE attacks

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.

Prevention of HAE attacks — clinical trial results by subject

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.

  • 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.

Prevention with CINRYZE reduced the severity and duration of HAE attacks and days of swelling

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)

Definition: