Lanadelumab 300mg/2ml solution for injection vials

Long-term prophylaxis (LTP) has been shown to reduce the frequency of hereditary angioedema (HAE) attacks; however, attacks occurring in patients receiving LTP have not been well characterized. The objective of this systematic review was to evaluate the proportion of type I/II HAE (HAE-C1INH) patients who experience attacks while receiving LTP, the characteristics of these attacks, and associated on-demand therapy use. A systematic search was conducted in PubMed to identify studies reporting LTP use with plasma-derived C1 inhibitor (pdC1INH), lanadelumab, berotralstat, androgens, or antifibrinolytics in patients with HAE-C1INH. Forty-five primary studies met the inclusion criteria. In phase 3 trials, attack-free rates were 40% for subcutaneous pdC1INH 60 IU/kg twice weekly at 16 weeks, and 44% for lanadelumab 300 mg every second week at 6 months (77% during steady-state [days 70-182]); there was no difference in attack-free rate for berotralstat 150 mg versus placebo at 24 weeks. Phase 3 studies reported a lower average attack severity with subcutaneous and intravenous pdC1INH versus placebo. With lanadelumab and berotralstat, the prophylactic treatment effect was more pronounced in peripheral attacks than in abdominal and laryngeal attacks. Laryngeal attacks accounted for 2%-7% of all attacks in observational and interventional studies, regardless of the LTP agent received. On-demand therapy was used in 49%-94% of attacks occurring in the presence of LTP. In conclusion, patients receiving LTP experienced attacks in all anatomic locations, including the larynx. Most attacks were treated with on-demand therapy, although outcomes were not reported. Access to on-demand therapy remains essential for all people with HAE-C1INH.

Abstract licence: CC BY

Background and objectiveHereditary angioedema presents as recurrent, unpredictable, and often debilitating attacks of cutaneous/submucosal swelling. This study assessed the characteristics and treatment patterns of patients receiving long-term prophylaxis with the plasma kallikrein inhibitor lanadelumab in US clinical practice.MethodsThis retrospective longitudinal study, based on a physician panel-based medical chart review, included patients with a diagnosis of hereditary angioedema due to C1 esterase inhibitor deficiency/dysfunction (HAE-C1INH-Type1/2), initiating lanadelumab in/after August 2018 (index date), and with ≥ 3 months' post-index follow-up (Part 1, N = 186) and, additionally, a dosing interval extension after initiating lanadelumab 300 mg every 2 weeks (Part 2, N = 75).ResultsPatients in Part 1 were predominantly aged ≥ 18 years (95.7%) with HAE-CINH-Type1 (90.3%); Part 2 included a higher proportion of patients with HAE-C1INH-Type2 (28.0% vs 9.7%). In Part 1, 115/165 (69.7%) patients with hereditary angioedema attack information experienced 371 attacks in the 3 months pre-index; these were mostly mild/moderate (60.4%) and most commonly affected the lips (38.0%) and hands (32.9%). In total, 19/155 (12.3%) patients had 39 attacks during the post-index period (mean ± standard deviation [interquartile range] attack rate: 0.1 ± 0.3 [0.0, 0.0] per month). In Part 2, a dosing interval extension was enabled by well-controlled disease (74/75, 98.7%); most patients (86.7%) transitioned from every 2 weeks to every 4 weeks dosing. Among patients with attack information, 7/72 (9.7%) experienced a hereditary angioedema attack while receiving an initial every 2 weeks dosing regimen and 4/75 (5.3%) after an extended-interval dosing regimen.ConclusionsLanadelumab dosing intervals can be individualized to maintain effective disease control. A dosing interval extension may be considered in well-controlled disease.

Abstract licence: CC BY-NC 4.0

Abstract Introduction: Hereditary angioedema (HAE) is a rare genetic disorder characterized by unpredictable, painful swelling attacks that significantly impair patients’ quality of life (QoL). Clinical trials of lanadelumab led to its approval for long-term prophylaxis in patients with HAE; however, real-world data on long-term lanadelumab use in patients with HAE are limited. This analysis describes real-world outcomes of patients with HAE who have received lanadelumab as long-term prophylaxis for ≥3 years. Methods: From January 2023 to January 2024, investigators collected data from the Adelphi Wave II Disease Specific Programme™, a real-world, cross-sectional survey of physicians and their patients with HAE in the USA. Physicians retrospectively reported attack frequency, attack severity, and QoL before lanadelumab initiation, at 12, 24, and 36 months post initiation, and at the time of the survey. Results: Physicians reported data on 51 patients who had received lanadelumab for ≥3 years. Before lanadelumab initiation, physicians reported attack severity as mild in 49.0% of patients and very severe in 8.2%; at 36 months post lanadelumab initiation, 62.5% of patients experienced mild attacks and none experienced very severe attacks in the preceding year. The proportion of patients experiencing ≥1 attack per month on average decreased from 54.0% before lanadelumab initiation to 9.8% at the time of the survey. The proportion of patients with good or excellent QoL increased from 68.6% before lanadelumab initiation to 88.2% at the time of the survey. Conclusion: In this real-world HAE study, patients treated with lanadelumab for ≥3 years experienced improvements in attack frequency, disease severity, and QoL.

Abstract licence: CC BY-NC