Sustained HAE Attack Reductions at 18 Months with Berotralstat, With Raffi Tachdjian, MD

In a large real-world cohort, berotralstat initiation was associated with significant reductions in monthly hereditary angioedema (HAE) attack rates at 12 months, with sustained benefit through 18 months across HAE subtypes and baseline severities.

“The exciting thing about this study is that it basically represents one of the largest real-world patient population cohorts that are receiving long-term prophylaxis for hereditary angioedema, and this included patients with normal C1 inhibitor HAE,” Raffi Tachdjian, MD, MPH, from the department of pediatrics at the University of California Los Angeles, told HCPLive. “This is a population in which the clinical data are limited.”

The retrospective analysis leveraged specialty pharmacy data from Optime Care, between December 2020 and January 2024. Investigators evaluated 390 patients with HAE with C1 esterase inhibitor (C1INH) and 311 with normal C1INH (HAE-nC1INH) who had at ≥ 2 dispensing and documented attack assessments before and after treatment initiation. Patients were stratified by baseline attack frequency (≥ 5, 2–4, 1, or 0 attacks per month).

Over 12 months, mean monthly attack rates fell 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), with reductions maintained through 18 months of follow-up. Reductions were observed regardless of baseline attack frequency or HAE subtype.

Among patients with ≥1 attack per month at baseline, initiation of berotralstat resulted in statistically significant declines in attack rates. Most patients with 0 baseline attacks per month-maintained attack-free status during follow-up (70–85% in HAE-C1INH; 61–81% in HAE-nC1INH), reinforcing the durability of response.

Tachdjian underscored the importance of re-discussing prophylactic options with clinicians. He characterized berotralstat as a viable first-line option or alternative for patients dissatisfied with injectable prophylaxis, particularly those with needle aversion or treatment fatigue. With recent label expansion down to age 2 years, he said that the oral agent now spans a broader pediatric-to-adult population.

“I don't think there remain too many unanswered questions as far as durability or tolerability,” Tachdjian said. “Obviously, we continue to have vigilance in any drug that's out there, but whether it's the specialty pharmacy data, obviously, the clinical trials, the pivotal phase 3 data that is read out, really point to the fact that this has efficacy and safety, both things we look for. In my mind…there's compliance with the regimen and reporting back on any kind of attacks or safety signals to make sure that they are being taken care of in this prophylactic environment.”