Real-World HAE Control with Berotralstat at 18 Months, With Raffi Tachdjian, MD

In the second part of his conversation with HCPLive, Raffi Tachdjian, MD, MPH, from the department of pediatrics at the University of California Los Angeles, further contextualized new real-world data demonstrating sustained reductions in hereditary angioedema (HAE) attack rates at 18 months following initiation of berotralstat (ORLADEYO).

Tachdjian emphasized that one of the most clinically meaningful aspects of the analysis is its scale and inclusion of patients with normal C1 inhibitor HAE (HAE-nC1INH), a subgroup historically underrepresented in clinical trials. The study cohort represents one of the largest real-world populations receiving long-term oral prophylaxis, offering insight into treatment performance beyond controlled trial settings.

The analysis included patients with HAE from Optimal Care (Dec 2020–Jan 2024) with ≥ 2 dispensings and documented attack assessments before and after treatment. Among the sample, 390 had a C1 esterase inhibitor (C1INH) deficiency, and 311 had normal C1INH (HAE-nC1INH).

Over 12 months, mean monthly attack rates decreased from 2.50 to 0.79 among patients with HAE-C1INH and from 4.59 to 1.68 among those with HAE-nC1INH (both P <.001). Reductions continued through 18 months of follow-up and were observed regardless of baseline attack frequency or HAE subtype.

In this Q&A, Tachdjian explains how to interpret the sustained attack reductions at 12 and 18 months, explores differences in response between HAE-C1INH and HAE-nC1INH that may influence treatment decisions, and discusses how these real-world data complement or differ from findings in clinical trials.

HCPLive: What is the most clinically meaningful takeaway from these real-world attack rate reductions following berotralstat initiation?

Tachdjian: The exciting thing about this study is that it represents one of the largest real-world patient population cohorts that are receiving long-term prophylaxis for hereditary angioedema, and this [includes] patients with normal C1 inhibitor HAE. This is a population in which clinical data are limited.

HCPLive: How should clinicians interpret the sustained reductions at 12 and 18 months when counseling patients about long-term prophylaxis expectations?

Tachdjian: The significant attack reductions observed at 12 months and sustained at 18 months in this study suggest that the clinical benefit of treatment with ORLADEYO can be maintained over time, including in patients with higher baseline disease activity and different HAE types. This provides additional context for treatment discussions, reinforcing that long-term prophylaxis with ORLADEYO can offer durable disease control for many patients—an essential objective in the management of hereditary angioedema.

HCPLive: Were there differences in response between HAE-C1INH and HAE-nC1INH that should influence treatment strategy?

Tachdjian: In this real-world study, we observed clinically and statistically meaningful differences in response for patients with HAE-C1INH and those with HAE-nC1INH, which is notable given the more limited evidence base in the latter group. These findings suggest that ORLADEYO could be considered as part of a long-term prophylactic strategy for people with HAE regardless of type.

HCPLive: How does real-world specialty pharmacy data complement—or differ from—what we learned in clinical trials?

Tachdjian: While clinical trials establish efficacy and safety in a controlled environment, real-world specialty pharmacy data show us how ORLADEYO performs across a diverse HAE population in routine clinical practice, including patients with varying disease severity and types. Seeing significant and sustained attack reductions outside the trial setting through a protocol-driven real-world study reinforces confidence in the role of ORLADEYO as a long-term prophylactic option across HAE types and disease severity.

References

1. Tachdjian R. HCPLive. Sustained HAE Attack Reductions at 18 Months with Berotralstat, With Raffi Tachdjian, MD. HCPLive. Published on February 16, 2026. Accessed on February 18, 2026. https://www.hcplive.com/view/sustained-hae-attack-reductions-18-months-berotralstat-raffi-tachdjian-md

2. Davis-Lorton M, Tachdjian R, Lopez-Gonzalez L, et al. Attack rate reductions following berotralstat initiation among US patients with hereditary angioedema in the real-world. Allergy Asthma Clin Immunol. Published online January 25, 2026. doi:10.1186/s13223-025-01005-x