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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.
During the first 26 weeks (days 0–182), five (41.7%) patients were attack-free.
directly measured in all 12 patients, with the small uncontrolled cohort limiting certainty
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.
large descriptive within-cohort reduction, but the uncontrolled baseline comparison cannot establish causation
There were no deaths or discontinuations due to TEAEs, no severe or serious TEAEs related to lanadelumab, and no positive anti-drug antibody results.
direct descriptive safety observations reported for the complete 52-week cohort
Results of this study support the findings from two global phase 3 studies for lanadelumab use as prophylactic therapy in Japanese patients with HAE.
directionally similar outcomes across studies, without formal comparison and with only 12 Japanese participants
The results of the study show the effectiveness of lanadelumab for prevention of HAE attacks in Japanese patients with HAE type I/II.
causal effectiveness wording exceeds what the uncontrolled open-label design can identify
Derived from the full evaluation — not a separate score.
Strengths
The pivotal global trials did not include Japanese patients, while this study directly evaluates the target population and is reported to have contributed to Japanese approval.
↳ Introduction, p. 1382; Discussion, p. 1388
The run-in, 52-week treatment periods, attack definitions, dose-modification rules, adverse-event collection, and descriptive analysis are specified, and all 12 patients completed the study.
↳ Methods §§2.1–2.5; Figures 1–2
The discussion compares attack-free status, attack-rate reductions, quality-of-life changes, and safety with HELP and HELP OLE while acknowledging numerical differences.
↳ Discussion, pp. 1388–1389
Limitations
The open-label pre/post design cannot separate treatment effects from temporal variation, regression to the mean, or altered reporting, and no hypothesis testing was performed.
↳ Methods §2.5; Discussion, p. 1389
After acknowledging that open-label treatment may influence outcome reporting, the conclusion states that the study shows effectiveness rather than providing supportive bridging evidence.
↳ Discussion, pp. 1389–1390
Only four attack-free patients switched to Q4W, one returned to Q2W after new attacks, and the paper acknowledges the short Q4W exposure and limited interpretability.
↳ Results §3.5; Figure 2; Discussion, pp. 1389–1390
The Japanese-specific bridge is clinically relevant and follows a detailed 52-week protocol with complete participant retention and transparent descriptive reporting. Tables 2 and 5 substantiate the observed attack and safety outcomes, while the discussion places them against HELP and HELP OLE. The uncontrolled open-label design and feasibility-based sample of 12 substantially limit causal inference, rare-harm assessment, and subgroup conclusions. The final effectiveness statement therefore lowers clarity, while the four-patient Q4W analysis constrains transferability and practical dosing guidance.
Nabu’s assessment, alongside the field’s view.
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Sound3.5
Confidence mediumThe study fills a documented Japanese-specific evidence gap and contributed to national regulatory approval. Its scientific advance is incremental because efficacy and safety had already been established in the global HELP program.
“contributed to the approval of lanadelumab use in Japan in March 2022”
Eligibility, dosing, attack confirmation, endpoints, safety collection, and the 52-week timeline are reported in detail, with descriptive analysis matched to the feasibility-based sample. The open-label, uncontrolled baseline comparison leaves temporal variation and reporting effects unresolved despite explicit acknowledgment.
“No statistical hypothesis testing was performed.”
The manuscript presents a traceable progression from the bridging rationale through methods, outcomes, and limitations. The final statement that the study shows effectiveness is less calibrated than the otherwise consistent language of support and directional consistency.
“The results of the study show the effectiveness of lanadelumab”
Findings are compared quantitatively with HELP and HELP OLE, and the discussion identifies small sample size, open-label reporting effects, and limited Q4W exposure. Contextualization is reduced by conclusions about effectiveness and regimen suitability that are stronger than those limitations warrant.
“Interpretation of the dosing subgroup analysis was limited”
Caveats4 of 4 checks
Reported participant counts, attack outcomes, confidence intervals, and adverse-event totals are internally consistent. The final effectiveness statement is stronger than the descriptive, uncontrolled design supports and affects interpretation rather than the underlying numerical results.
Ethics, consent, registration, conflicts, funding, and sponsor participation are disclosed. Sponsor involvement extended to study design, conduct, data management and analysis, and manuscript review, making it a material but transparent contextual consideration.
Flags: 3 declared / 5 total
22 of 22 checkable references verified
28 references in manuscript 6 are books, websites or datasets — counted, but not index-checkable the reference list may be incompletely parsed; counts are indicative
No retraction notice found in Retraction Watch.
Sources: Retraction Watch ✓
Where this paper’s evidence sits on the path from initial observation to real-world use.
The study evaluates the approved dosing approach directly in the target Japanese population and informed a regulatory decision. Readiness remains short of broad deployment evidence because the investigation is a small, uncontrolled bridge rather than post-marketing practice data.
“a phase 3, multicenter, open-label study”
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