Effectiveness and safety of lanadelumab in ethnic and racial minority subgroups of patients with hereditary angioedema: results from phase 3 studies

Abstract

Background: The COVID-19 pandemic has highlighted disparities in healthcare, particularly in the United States, even though disparities have existed since the organization of the modern healthcare system. Recruitment of patients from racial and ethnic minority groups is often minimal in phase 3 clinical trials, and is further exacerbated in the case of trials for rare diseases such as hereditary angioedema (HAE). This can lead to a gap in the understanding of minority patients' experiences with these diseases and their response to potential treatment options.

Methods: We reviewed data from phase 3 double-blind (HELP) and open-label extension (HELP OLE) trials of lanadelumab, a monoclonal antibody developed for long-term prophylaxis against attacks of HAE. Efficacy (attack rate reduction) and safety (adverse events) results from White patients were compared descriptively to those from Hispanic/Latino patients, Black/African Americans, and other minority Americans.

Results: Not surprisingly, few minorities were recruited across both studies: 9.5% Black, 2.4% Asian, and 7.1% Hispanic/Latino versus 88.1% White and 91.7% non-Hispanic/non-Latino received lanadelumab in HELP, and 4.7% Black, 0.9% Asian, 0.9% other, and 6.1% Hispanic/Latino versus 93.4% White and 93.4% non-Hispanic/non-Latino were enrolled in HELP OLE. Although these studies were conducted in the United States, Canada, Europe, and Jordan, all minorities were from the United States. Despite the number of minority patients being far less than expected for the population, there was no evidence that either efficacy or adverse event profiles differed between ethnic or racial groups.

Conclusions: The HELP and HELP OLE studies described herein recruited far fewer minorities than would be ideal to represent these populations. However, evidence suggests that the effectiveness and tolerance of lanadelumab are similar between the groups. Nonetheless, the disparity in recruitment into research for minorities has significant room for improvement. Trial registration NCT02586805, registered 26 October 2015, https://ichgcp.net/clinical-trials-registry/NCT02586805 . NCT02741596, registered 18 April 2016, https://ichgcp.net/clinical-trials-registry/NCT02741596 .

Keywords: Disparity; Ethnicity; Hereditary angioedema; Lanadelumab; Long-term prophylaxis; Race.

Conflict of interest statement

TJC: speaker and researcher for BioCryst, CSL-Behring, and Takeda. Researcher for KalVista and Pharvaris. Speaker for Grifols. Consultant for BioMarin and Spark. Director ACARE International Hereditary Angioedema Center. Medical Advisory Board for the HAE-A. Board of Directors for the AAAAI. RHZ-U: received consulting fees from BioCryst and Takeda, and lecture fees from Dyax, Pharming, and Takeda. HHL: received grants, personal fees, and non-financial support from CSL Behring, Pharming, and Takeda. MY, SJ: full-time employees of and own stocks/options in Takeda. HR: full-time employee of Cytel, which was contracted by Takeda to conduct statistical analyses. JA: speaker bureau member for CSL Behring, Pharming, and Takeda; and has received consultancy fees from and is a clinical trial investigator for BioCryst, CSL Behring, Pharming, and Takeda.

© 2022. The Author(s).

Figures

Fig. 1

A Patients attack free 0–6 months after treatment initiation* and B with ≥ 70% attack rate reduction during treatment.* Data for all lanadelumab doses in the HELP study are pooled. OLE open-label extension, q2w every 2 weeks, q4w every 4 weeks. *Regular dosing stage for rollover patients in the HELP OLE study. †Only 1 Black/African American patient was in the lanadelumab 300 mg q2w treatment group. ‡Both Asian patients were in the lanadelumab 150 mg q4w treatment group