Criteria
Placebo
Lanadelumab
150 mg q4wks
300 mg q4wks
300 mg q2wks
Treatment period (Day 0 to Day 182, 26 weeks)
n
41
28
29
27
Attack free
2%
39%
31%
44%
The percentage of patients who were attack free for the last 16-weeks (Day 70 to Day 182) of the study was 77% in the 300 mg q2wks group, compared to 3% of patients in the placebo group.
100% of the subjects on 300 mg q2wks or q4wks and 89% on 150 mg q4wks achieved at least a 50% reduction in HAE attack rate compared to the run-in period.
Health related Quality of Life
All TAKHZYRO treatment groups observed an improvement in Angioedema Quality of Life Questionnaire (AE-QoL) total and domain (functioning, fatigue/mood, fear/shame, and nutrition) scores compared to the placebo group; the largest improvement was observed in the functioning score as shown in Table 4. A reduction of 6 points is considered a clinically meaningful improvement. The percentage of patients who achieved a clinically meaningful improvement in AE-QoL total score was 65% (Odds ratio vs placebo, [95% CI]= 3.2 [1.1, 9.2]), 63% (2.9 [1.1, 8.1]), and 81% (7.2 [2.2, 23.4]), in TAKHZYRO 150 mg q4 wks, 300 mg q4 wks, and 300 mg q2 wks groups, respectively, compared to 37% of patients in the placebo group.
Table 4 Change in AE-QoL scorea - placebo vs TAKHZYRO at week 26 in HELP study
LS mean change (SD) from baseline at week 26
Placebo
TAKHZYRO total
AE-QoL Total score
-4.7 (18.8)
-19.5 (18.6)
Functioning score
-5.4 (22.7)
-29.3 (22.9)
Fatigue/Mood score
-1.8 (23.3)
-13.0 (23.1)
Fear/Shame score
-9.0 (24.0)
-18.8 (23.7)
Nutrition score
0.5 (22.5)
-17.0 (22.3)
Note: AE-QoL= Angioedema Quality of Life; LS=least squares; SD=standard deviation.
a Lower scores indicate lower impairment (or better health-related quality of life).
HELP study extension
Long-term safety and efficacy of TAKHZYRO for prophylaxis to prevent HAE attacks was eva luated in an open-label HELP study extension.
A total of 212 adult and adolescent subjects with symptomatic type I or II HAE received at least one dose of lanadelumab in this study, including 109 subjects who entered as rollover subjects from the HELP study and 103 new or non-rollover subjects (including 19 subjects from Phase1b study) who had an historical baseline attack rate of ≥1 attack per 12 weeks Subjects were allowed to initiate self-administration after receiving the first 2 doses from a health care professional in clinic and completing appropriate training. Interim analysis indicates that the effect was sustained up to one year of treatment.
Paediatric population
The European Medicines Agency has deferred the obligation to submit the results of studies with TAKHZYRO in one or more subsets of the paediatric population in the prevention of hereditary angioedema attacks.
5.2 Pharmacokinetic properties
The single and multiple dose pharmacokinetics of lanadelumab have been studied in patients with HAE. Pharmacokinetics of lanadelumab showed linear dose-exposure response with doses up to 400 mg and reproducible exposure following subcutaneous administration up to 12 months. The absolute bioavailability of lanadelumab after subcutaneous administration has not been determined. In the HELP study, patients treated with 300 mg q2 wks presented mean (SD) area under the curve over the dosing interval at steady-state (AUCtau,ss), maximum concentration at steady-state (Cmax,ss) and minimum concentration at steady-state (Cmin,ss) of 408 µg*day/ |
