Efficacy and safety of lanadelumab in Japanese patients with hereditary angioedema: A phase 3 multicenter, open‐label study

The safety and efficacy of lanadelumab for the prevention of hereditary angioedema (HAE) attacks have not been studied in Japanese patients. We report outcomes from a phase 3, multicenter, open‐label study (NCT04180163) of lanadelumab in Japanese patients with HAE. Japanese patients with HAE aged ≥12 years with ≥1 investigator‐confirmed HAE attack during the 4‐week run‐in baseline period were enrolled into the study and received lanadelumab 300 mg every 2 weeks subcutaneously for 52 weeks. Dosing could be reduced to 300 mg every 4 weeks during the second 26‐week treatment period if patients had well‐controlled symptoms (e.g., attack‐free) for 6 months. The primary efficacy endpoint was no investigator‐confirmed HAE attacks (attack‐free status) during days 0–182. Other outcomes included the rate of investigator‐confirmed HAE attacks per month (28 days) and lanadelumab safety. Twelve patients (mean ± SD age 41.9 ± 12.4 years) were enrolled. During the first 26 weeks (days 0–182), five (41.7%) patients were attack‐free. The mean ± SD HAE attack rate per month decreased by 74.0%, from 3.8 ± 2.4 during baseline to 1.2 ± 2.6 during the overall 52‐week treatment period. There were no deaths or discontinuations due to treatment‐emergent adverse events (TEAEs), no severe or serious TEAEs related to lanadelumab, and no positive anti‐drug antibody results. The most frequent TEAEs were injection‐site reactions (37 events in six patients). Most of the injection‐site reaction adverse events were mild in severity. Results of this study support the findings from two global phase 3 studies for lanadelumab use as prophylactic therapy in Japanese patients with HAE.

only first-line LTP treatment approved in Japan. 11nadelumab is a fully human monoclonal antibody inhibitor of active plasma kallikrein, developed for the prevention of angioedema attacks in patients with HAE type I/II. 12In the pivotal global HELP study, treatment with lanadelumab 300 mg every 2 weeks (Q2W) significantly decreased HAE attack rates by 87% over 26 weeks of treatment compared with placebo, and approximately 44% of patients achieved attack-free status. 13Sustained efficacy and safety were confirmed in the HELP open-label extension (HELP OLE) study, which provided the data on the outcomes of long-term lanadelumab treatment over a mean ± SD of 29.6 ± 8.2 months; 14 in the HELP OLE study, lanadelumab 300 mg Q2W reduced the mean HAE attack rate by 87.4% versus baseline. 14The results of the HELP and HELP OLE studies led to the approval of lanadelumab for the prevention of HAE attacks in patients aged ≥12 years in multiple countries and regions, including the United States, 15 Canada, 16 and the European Union. 17Furthermore, lanadelumab indication in the United States was expanded to include pediatric patients aged ≥2 years in February 2023. 15e clinical features of HAE were reported to be similar between Japanese and European patients, with the possible exception of abdominal symptoms. 18,199][20][21] Therefore, therapies such as lanadelumab that have proven efficacy and safety in global populations may be beneficial to Japanese patients with HAE, but data on outcomes with lanadelumab specific to Japan are lacking.To bridge the gap between data on the global lanadelumab outcomes and the outcomes in Japanese patients with HAE , a phase 3, multicenter, open-label study (NCT04180163) was conducted to evaluate the efficacy and safety of lanadelumab in Japanese patients with HAE type I/II.The results of this study added to the evidence base from the global HELP and HELP OLE studies and contributed to the approval of lanadelumab use in Japan in March 2022. 22

| Patient eligibility
Patients of Japanese descent (defined as being born in Japan and having Japanese parents and paternal and maternal grandparents) aged ≥12 years were eligible for inclusion in the study.One of the inclusion criteria was a documented diagnosis of HAE type I/II, confirmed by a C1-INH functional level of <40% of the normal, or a C1-INH functional level of 40%-50% of the normal and C4 below normal at screening.Furthermore, to be included in the study, the patients had to have ≥1 investigator-confirmed HAE attack during the 4 weeks of the run-in period.Key exclusion criteria included a concomitant diagnosis of another form of chronic recurrent angioedema, use of shortterm HAE prophylaxis within the 7 days prior to entering the run-in period, use of long-term HAE prophylaxis or exposure to androgens within the 2 weeks prior to entering the run-in period, and exposure to angiotensin-converting enzyme inhibitors or any estrogen-containing medications with systematic absorption within 4 weeks prior to screening.Full inclusion/exclusion criteria are listed in Table S1.

| Study design
This phase 3 study was conducted at 10 study sites in Japan from Acute HAE attacks during the study were treated according to the local standard of care.LTP for HAE, angiotensin-converting enzyme inhibitors, estrogen-containing medications, and androgens were prohibited, but short-term prophylaxis of HAE attacks was permitted if medically indicated.Short-term prophylaxis refers to onetime prophylactic treatment administered to reduce the potential risk of HAE attacks before situations (e.g., surgical, dental, or other medical procedures) known to be associated with an increased risk of attacks. 4Short-term prophylaxis during the study followed the local standard of care.No guidance on the choice of medications for short-term prophylaxis or their dosing was provided, except for the prohibition of androgen use for short-term prophylaxis.
At the end of the overall 52-week treatment period (days 0-364), patients were eligible to roll over into an expanded access study (TAK-743-5007, NCT04687137) or complete a 4-week safety follow-up and exit the study.The patients who chose to roll over to the TAK-743-5007 study were to return on day 378.All other patients were to continue the study and return on day 392.
This study was conducted in compliance with the Institutional Review Board/Independent Ethics Committee regulations stated in the Good Clinical Practice regulations, in accordance with the principles of the Declaration of Helsinki, and all applicable local regulations.Informed consent/assent (as applicable) was obtained for all patients enrolled in the study.

| Outcome measures
All HAE attacks analyzed for the efficacy endpoints were confirmed by the investigators.Patients reported details of the HAE attack within 72 h of the onset of the attack.All patient-reported HAE attacks, regardless of confirmation by study investigator, were used in a sensitivity analysis.The primary efficacy endpoint was the achievement of attack-free status for the first 26-week treatment period (days 0-182), with attack-free status defined as no investigatorconfirmed HAE attacks during this period.Other efficacy endpoints included rates per month (defined as 28 days) for all HAE attacks, HAE attacks requiring acute treatment, high-morbidity HAE attacks (defined as ≥1 of the following: severe; resulting in hospitalization except hospitalization for observation <24 h; hemodynamically significant; and/or laryngeal), and percentage of attack-free days.
Patients who achieved specified thresholds of ≥50%, ≥70%, and ≥90% reduction in the number of HAE attacks per month relative to the run-in period were defined as responders.Additional responder analysis was performed for patients who achieved specified thresholds of <1.0, <0.75, <0.5, and <0.25 HAE attacks per month.Attack rates during the steady-state periods (days 70-182 and days 70-364, as based on the 14-day half-life of lanadelumab) 23 were also analyzed.
Health-related quality of life (HRQoL) was assessed using the Angioedema Quality of Life (AE-QoL) questionnaire -an angioedema-specific quality-of-life instrument with a validated Japanese version. 24,25The AE-QoL questionnaire consists of four domains (Functioning, Fatigue/Mood, Fears/Shame, Nutrition) and 17 items.The AE-QoL scores range from 0 to 100, with higher scores reflecting higher impairment and lower quality of life. 26A change of 6 points in the AE-QoL total score reflects a minimal clinically important difference. 26I G U R E 1 Study design.† Patients who experienced ≥3 investigator-confirmed hereditary angioedema (HAE) attacks before the end of the 4-week run-in period could exit the run-in early and proceed to the first 26-week treatment period.Patients who did not experience investigator-confirmed HAE attacks in the 4-week run-in period could have their run-in extended to 8 weeks; they were required to complete the full 8 weeks of run-in and have ≥2 investigator-confirmed HAE attacks during the run-in to be eligible for the study.‡ Patients who chose to roll over to the TAK-743-5007 study were to return on day 378.All the other patients were to continue the study and return on day 392.LTP, long-term prophylaxis; Q2W, every 2 weeks; Q4W, every 4 weeks.Subgroup analysis was performed in patients who switched dosing from 300 mg Q2W to 300 mg Q4W.Attack rates per month as well as changes from the baseline were compared for the Q2W dosing period (any period during which the patient received lanadelumab 300 mg Q2W) and the Q4W dosing period (any period during which the patient received lanadelumab 300 mg Q4W).

| Adverse events and anti-drug antibodies
Adverse events (AEs), including serious AEs and AEs of special interest (AESIs: hypersensitivity reactions and disordered coagulation, including hypercoagulability and bleeding events) were collected by the investigator or a qualified designee by questioning and/or examining the patients from the signing of informed consent through the final follow-up visit.The questioning was generalized and the patients were not explicitly questioned about the presence or absence of specific AEs.AEs were coded using the Medical Dictionary for Regulatory Activities, version 24.0.HAE attacks were captured as both efficacy events and AEs in this study.To avoid complicating the interpretation of safety, only non-HAE attack AEs were analyzed as safety events.
Immunogenicity was measured based on the presence or absence of anti-drug antibodies (ADAs), including neutralizing ADAs, in plasma.Samples were collected within 2 h prior to dosing.

| Statistical analysis
Based on feasibility considerations, the planned total sample size for this study was ≥8 patients.No formal sample size calculation was performed.All efficacy, safety, and HRQoL analyses were performed in the full analysis population, which included all patients who received ≥1 dose of lanadelumab.No statistical hypothesis testing was performed.Descriptive statistics were calculated for continuous and categorical variables.Time to event for the first HAE attack was summarized using a Kaplan-Meier estimate.The totality of results across all efficacy endpoints was used as a measure of overall treatment benefit, with the primary goal of demonstrating consistency with the global HELP study, especially for the primary efficacy endpoint.

| Patient characteristics
A total of 12 patients with HAE type I/II were enrolled, and all 12 have completed the study (Figure 2).The mean ± SD age was 41.9 ± 12.4 years, and 75.0% of patients were female (Table 1).The mean ± SD age at HAE symptom onset was 21.5 ± 12.9 years.The mean ± SD attack rate during the run-in period was 3.8 ± 2.4 attacks per month, and 66.7% of patients were experiencing ≥3 attacks per month.Half of the patients (50%) reported previous use of LTP, and all of them had used an antifibrinolytic for their LTP of HAE attacks.

| Efficacy endpoints
Five patients (41.7%; 95% confidence interval [CI] 15.2-72.3)achieved the primary endpoint of attack-free status (no investigatorconfirmed HAE attacks) during the first 26-week treatment period (Table 2).The median time from day 0 to the first HAE attack in the first 26-week treatment period was 97.2 days (95% CI 4.2 to not applicable) (Figure S1).
The efficacy results are summarized in  S2.

| Steady-state analysis
During the steady state of the first 26-week treatment period (days 70-182), the mean ± SD rate of HAE attacks per month was 1.1 ± 2.5, corresponding to a change from a baseline of −2.7 ± 1.3, or an 80.3% reduction from the baseline attack rate (Table 2).
During the steady state of the overall 52-week treatment period (days 70-364), the mean ± SD rate of HAE attacks per month was 1.2 ± 2.6, corresponding to a change from baseline of −2.6 ± 1.5, or 74.4% reduction from the baseline attack rate.

| Health-related quality of life
The mean ± SD AE-QoL total score decreased during the first 26week treatment period, from 46.6 ± 20.9 at day 0 to 26.1 ± 34.0 at day 182 (a −20.5 ± 21.7 change from baseline) (Table 3).The AE-QoL score remained stable during the second 26-week treatment period, with a mean ± SD AE-QoL total score of 26.6 ± 34.4 at day 364 and a mean ± SD change in score from day 0 of −20.0 ± 21.9.
Each domain score (Functioning, Fatigue/Mood, Fear/Shame, and Nutrition) also decreased by ≥15 points during the first 26-week treatment period, and ≥10-point reductions in domain scores persisted during the overall 52-week treatment period.

| Subgroup analysis
The rates of HAE attacks per month in the four (33.3%) patients who switched dosing from 300 mg Q2W to 300 mg Q4W were low during both dosing periods (a mean ± SD of 0.1 ± 0.2 during the Q2W dosing period and 0.1 ± 0.2 during the Q4W dosing period).There were no notable differences in efficacy before and after switching from 300 mg Q2W to 300 mg Q4W dosing (Table 4).
TA B L E 1 Patient baseline characteristics.

| Lanadelumab safety
Eleven patients (91.7%) reported at least one treatment-emergent AE (TEAE), excluding HAE attacks, for a total of 180 TEAEs reported during the overall 52-week treatment period.TEAEs in the first and second 26-week treatment periods as well as in the overall 52-week treatment period are summarized in Table 5, and a full list of TEAEs occurring in the overall 52-week treatment period is provided in Table S3.The TEAEs reported in at least two patients during the overall 52-week treatment period, regardless of their relationship with the study treatment, were injection-site reactions (37 events in six patients); headache (13 events in three patients); injectionsite erythema (nine events in three patients); nasopharyngitis (four events in two patients); pyrexia and vomiting (three events in two patients each); cystitis, injection-site pruritus, and oropharyngeal pain (two events in two patients each).
TA B L E 2 Efficacy outcomes.

Primary endpoint All patients (N = 12)
Achievement of attack-free status from day 0-182, n (%; 95% CI) Note: Month was defined as 28 days.Baseline values refer to the values from the run-in period.
These included injection-site reactions (36 events in six patients), headache (10 events in two patients), injection-site erythema (seven events in two patients), palpitations (21 events in one patient), nausea (20 events in one patient), vertigo (three events in one patient), malaise (two events in one patient), injection-site pain, injection-site pruritus, injection-site swelling, and decreased appetite (one event in one patient each).No severe TEAEs or serious AEs were considered related to lanadelumab treatment, and there were no deaths or discontinuations due to TEAEs.
One patient (8.3%) had one severe non-HAE TEAE (anxiety disorder), which was classed as a serious TEAE and considered to be not related to lanadelumab treatment by the investigator.Two patients (16.7%) had three serious TEAEs (excluding HAE attacks): two events of device-related infection and one event of anxiety disorder (described above).All serious TEAEs were considered to be not related to lanadelumab treatment by the investigators and were resolved.
During the overall 52-week treatment period, 12 patients received a total of 299 injections of lanadelumab.A total of 50 AEs involving the injection site were reported in seven patients (58.3%).
These included injection-site reaction (37 events in six patients), injection-site erythema (nine events in three patients), injection-site pruritus (two events in two patients), injection-site pain (one event in one patient), and injection-site swelling (one event in one patient).
Most of the injection-site reaction AEs were mild in severity, and only one patient reported a moderate injection-site reaction AE.
During the second 26-week treatment period, seven patients (58.3%) received ≥1 dose of lanadelumab administered by the patient or their caregiver; a total of 59 doses of lanadelumab were self-administered.The self-administration of lanadelumab was not associated with an increase of TEAEs: during the second 26-week treatment period, there were 55 TEAEs in six of seven patients with study staff administration in clinic and 11 TEAEs in three of seven patients with self-administration (Table 6).
Investigator-reported AESIs included a total of 10 events in three patients (25.0%): eight events of injection-site reaction and one event each of injection-site swelling and gingival bleeding.All these events were mild and considered related to lanadelumab treatment by the investigators, except for gingival bleeding, which was moderate and considered to be not related to lanadelumab treatment.All the investigator-reported AESIs were resolved.No hypercoagulability AESIs were reported.
Activated partial thromboplastin time was longer than the upper limit of normal (ULN) in five patients, and prothrombin time was longer than ULN in three patients.However, none of these changes were deemed to be clinically significant by the investigators.All of them were reported during scheduled study visits and

TA B L E 4
Subgroup analysis by dosing period in patients with dose modification.
were not associated with a bleeding AE, and none were recorded None of the patients had a positive ADA result.

| DISCUSS ION
The clinical evidence of lanadelumab for LTP to prevent HAE attacks is primarily based on the results of two global, phase 3 studies: the HELP study and the HELP OLE study.The HELP study randomized 125 patients and compared three doses of lanadelumab (150 mg Q4W, 300 mg Q4W, and 300 mg Q2W) with placebo over 26 weeks of treatment. 13The HELP OLE study investigated the efficacy and safety of lanadelumab 300 mg Q2W in 212 patients over a mean of 29.6 months. 14However, neither of these global trials included patients from Japan. 13,27e study described here was designed to bridge the gap between data on the global lanadelumab outcomes and the outcomes in Japanese patients with HAE.Therefore, the Japanese study design was similar to the global phase 3 studies with consistent key inclusion criteria of HAE type I/II diagnosis and a patient age of ≥12 years. 13,14e requirements for 2-week washout from previous LTP (if applicable) and ≥1 investigator-confirmed HAE attack per the 4-week run-in period (or ≥2 HAE attacks per the 8-week run-in period) were also consistent with the HELP study, with the aim of achieving a similarity in baseline clinical presentation between the studies. 13Interestingly, the reported age at the HAE symptom onset was higher than the HELP study (a mean ± SD of 21.5 ± 12.9 and 13.0 ± 9.2, respectively), which may be related to low disease awareness in Japan.
Abbreviations: AE, adverse event; AESI, adverse event of special interest; HAE, hereditary angioedema; n, number of patients experiencing the event; [n] number of adverse events; MedDRA, Medical Dictionary for Regulatory Activities; TEAE, treatment-emergent adverse event.
a Treatment-related TEAEs were defined as TEAEs classified as related to lanadelumab treatment by the investigator.b Severe TEAEs were defined as severe (grade 3) or life-threatening (grade 4) by the investigator.
c AESIs were defined as hypersensitivity reactions and disordered coagulation events (bleeding and hypercoagulability).
| 1389 During the first 26-week treatment period, 41.7% of Japanese patients did not have investigator-confirmed HAE attacks during the treatment with lanadelumab 300 mg Q2W.These results are similar to those of the HELP study, in which 44.4% of patients treated with lanadelumab 300 mg Q2W for 26 weeks achieved attack-free status. 13Japanese patients also achieved reductions from baseline in number of HAE attacks per month for HAE attacks overall, HAE attacks requiring acute treatment, and high-morbidity HAE attacks.
The attack rate reductions were directionally consistent, albeit numerically lower, versus the reductions from baseline observed in the global HELP OLE study (74.0%during the overall treatment period in this study vs. 87.4% in HELP OLE), 14 which was possibly due to data variability in the small population of patients included in this study.Furthermore, the reductions in the HAE attack rates were numerically higher during the state, which is consistent with the lower HAE attack rate during the steady state of lanadelumab treatment as reported in the HELP study. 13erall, the Japanese patients achieved low attack rates with lanadelumab treatment, with the majority of patients achieving ≥50% reduction in HAE attack rates (10/12 patients) and attack rate of <0.5 attacks/month (7/12 patients) during the overall 52-week treatment period.Furthermore, in four patients who were attackfree for 26 consecutive weeks in the study and had dose modification to 300 mg Q4W during the second 26-week treatment period, HAE attack rates remained low during both dosing periods.Only one patient who received dose modification switched back to 300 mg Q2W dosing, and the other three patients remained on 300 mg Q4W dosing.This suggests that lanadelumab 300 mg Q4W dosing may be a suitable regimen for eligible Japanese patients, in line with the recommended dosing modification in the United States and Europe. 15,17QoL improvement in patients with HAE receiving lanadelumab for prevention of HAE attacks has been previously reported in a subanalysis from the global HELP study. 28In the Japanese study, the with the results from the HELP study. 28e safety of lanadelumab was consistent with the safety observed in the global HELP and HELP OLE studies. 13,14Injectionsite reactions were the most frequent TEAEs, and the majority of  Any TEAE, n (%), [n] 6 (85.7), [55] 3 (42.9),[11]   Any treatment-related TEAE a 1 (14.3),[24]  1 (14.3),[4]   Any serious TEAE 1 (14.design with placebo would overcome the ethical challenge of the long placebo treatment duration in patients with HAE.Interpretation of the dosing subgroup analysis was limited due to the low number of patients who switched dosing regimen and the short duration on 300 mg Q4W dosing.
The results of the study show the effectiveness of lanadelumab for prevention of HAE attacks in Japanese patients with HAE type I/ II.The efficacy and safety of lanadelumab in Japanese patients was consistent with the efficacy and safety reported in global phase 3 lanadelumab studies that enrolled adults and adolescents.

December 12 ,
2019, to August 26, 2021.The study design is shown in Figure 1.Briefly, after signing the informed consent form, patients underwent screening assessments.Patients aged ≥18 years who were receiving LTP were required to undergo a minimum 2-week washout period prior to entering the run-in period, as long as it did not put them in any undue safety risk as determined by the investigator.Eligible patients were enrolled and entered a 4-week run-in period to determine their baseline attack rate; baseline data on other efficacy and safety outcomes were also collected.Patients who experienced ≥3 investigator-confirmed HAE attacks before the end of the 4-week run-in period could exit run-in early and proceed to the treatment period.Patients without ≥1 investigator-confirmed HAE attack during the 4-week run-in period could have their run-in extended for another 4 weeks; to be eligible for the treatment period, they were required to complete the entire 8-week run-in period with ≥2 investigator-confirmed HAE attacks.During the first 26-week treatment period (days 0-182), patients received 300 mg lanadelumab Q2W as a subcutaneous administration from a single-use vial by the study personnel.Lanadelumab 300 mg Q2W is the approved starting dose in the United States and Europe. 15,17After completing the first 26-week treatment period, patients entered the second treatment period and continued to receive subcutaneous lanadelumab for another 26 weeks (days 183-364).During the second 26-week treatment period, individual patients could stay on lanadelumab 300 mg Q2W or consider lanadelumab 300 mg every 4 weeks (Q4W) if their symptoms were well-controlled (e.g., attack-free) for 26 consecutive weeks during the overall treatment period.The dose frequency change was based on the investigator's discretion and approval by the sponsor's medical monitor.Furthermore, during the second 26-week treatment period, single-use syringes prefilled with lanadelumab were available and self-administration by the patient or their caregiver was allowed with appropriate training and understanding of self-administration.| 1383 HIDE et al.

for
>1 consecutive study visit.There were no categorical shifts from normal to abnormal in vital sign results or clinical laboratory test results; clinically significant abnormalities were either present since before day 0 or transient.Clinically significant abnormalities present since before day 0 included high values for serum glucose and low values for serum sodium in one patient; high values for systolic and diastolic blood pressure in one patient; and high urine glucose and positive urine protein in one patient, who also had transient positive urine nitrite that was only observed on day 0.There were no clinically significant changes in any hematology values, no liver enzyme elevation >3 ULN, and no clinically significant electrocardiogram abnormalities.
There are several limitations to this study.The total number of patients enrolled in this study was low; however, it was higher than the estimated enrollment of eight patients given the relatively low number of HAE patients diagnosed in Japan and the requirement for ≥1 investigator-confirmed HAE attacks during the run-in period.Another limitation of this study was that due to the open-label design, patients were aware that they were receiving active treatment, which may have influenced the reporting of study outcomes.However, HAE attacks are an objective clinical presentation.It was considered unethical to expose the patients to placebo treatment given the severity of the patients' disease at enrollment and the established efficacy and safety of the study medication in the global population.Considering the 1-year study duration required by regulatory authorities, neither a double-blind design nor a cross-over TA B L E 6 Summary of TEAEs (excluding HAE attack-related events) during the second 26-week treatment period by the method of administration.
Abbreviations: AESI, adverse event of special interest; HAE, hereditary angioedema; n, number of patients experiencing the event; [n] number of adverse events; TEAE, treatment-emergent adverse event.aTreatment-related TEAEs were defined as TEAEs classified as related to lanadelumab treatment by the investigator.b Severe TEAEs were defined as severe (grade 3) or life-threatening (grade 4) by the investigator.c AESIs were defined as hypersensitivity reactions and disordered coagulation events (bleeding and hypercoagulability).
. The rate of HAE attacks per month during the first 26-week treatment period compared with baseline was reduced by 77.1%.Attack rates were also reduced by 75.2% for HAE attacks requiring acute treatment, byF I G U R E 2and 72.3% reduction for high-morbidity HAE attacks.The results of the sensitivity analysis using all subject-reported HAE attacks as opposed to investigator-confirmed HAE attacks were similar (data not shown).HAE attacks during the overall study period for individual patients are presented in FigureS2.
Quality of life.
TA B L E 3 AE-QoL score was reduced by approximately 20 points versus baseline during the first 26 weeks of treatment with lanadelumab, and the score remained stable during the second 26-week treatment period.This change in AE-QoL total score was larger than the minimal clinically important difference of 6 points, 26 suggesting clinically significant improvement in HRQoL in Japanese patients receiving lanadelumab.These results are similar to the results from the HELP study, where AE-QoL total score decreased by 21.29 points during 26 weeks of treatment with lanadelumab 300 mg Q2W.Decreases in every AE-QoL domain score (Functioning, Fatigue/Mood, Fears/ Shame, Nutrition) in Japanese patients were also observed, in line administration.Importantly, there were no increases in TEAEs reported in patients who self-administered lanadelumab.This suggests that self-administration may be suitable for lanadelumab treatment in Japanese patients with appropriate training.