Garadacimab, berotralstat reduce attacks in hereditary angioedema

Patients who are suffering from hereditary angioedema (HAE) may find comfort by using drugs that have been recently shown to ease HAE attacks. Treatment with either garadacimab or berotralstat results in reduced attack rates, according to studies presented at AAAAI 2024.

“Garadacimab demonstrated a favourable safety profile and reduced monthly attack rate in adolescents, consistent with previously reported overall population data,” said the researchers led by Joshua Jacobs, Allergy and Asthma Clinical Research, Walnut Creek, California, US.

On the other hand, long-term prophylaxis with berotralstat led to “rapid and sustained reductions in HAE attack rates, regardless of baseline attacks,” according to researchers headed by Mark Davis-Lorton, ENT and Allergy Associates, LLP, Tarrytown, New York, US.

Garadacimab

In the phase III VANGUARD study, six adolescents (aged 12 to 17 years, HAE with C1-esterase inhibitor deficiency) were randomly assigned to receive either garadacimab 200 mg subcutaneous once-monthly after 400-mg loading dose (n=4) or volume-matched placebo (n=2).

Jacobs and his team enrolled all participants in the open-label extension (OLE, second interim analysis), including five newly enrolled adolescents. These participants received garadacimab 200 mg (n=10; one patient aged 18 years at OLE enrolment was thereafter analysed as an adult).

The median cumulative garadacimab 200-mg exposure at data cutoff was 16.3 months across the pivotal phase III and OLE studies. [AAAAI 2024, abstract AB6]

Four of the six participants (67 percent) in the phase III study experienced at least one treatment-emergent adverse event (TEAE), while seven in 10 adolescents (70 percent) in the OLE had one or more TEAE. All AEs were mild or moderate in severity, and none were related to treatment.

Researchers did not observe any serious TEAEs, TEAEs leading to discontinuation or death, or AEs of special interest per protocol (ie, thromboembolic or abnormal bleeding events and severe hypersensitivity or anaphylaxis).

In the OLE, the mean attack rate per month was 0.09 on garadacimab compared with 1.86 during run-in (91.5 percent decrease). Of the 10 adolescents, four had no HAE attacks up to 17.0 months.

Berotralstat

In the real-world study of berotralstat, Davis-Lorton and his team obtained data through the sole-source pharmacy and included patients with HAE type I/II who actively received berotralstat 110 or 150 mg for up to 540 days between 16 December 2020 and 15 June 2023, stratified by baseline attacks.

Rates of baseline attacks were reported for the 90 days before treatment initiation and converted to a 30-day average for each patient.

The median attack rate remained 0 attacks/month for 450/540 days in 52 patients with 0 attacks in the 90 days prior to berotralstat initiation. [AAAAI 2024, abstract AB4]

Among those reporting 1‒3 attacks at baseline before berotralstat treatment (n=109), the median baseline attack rate dropped to 0.25 attacks/month from 0.67 attacks/month through day 90 and remained below baseline.

In 89 patients with 4‒9 attacks at baseline prior to treatment initiation, the median baseline attack rate decreased to 0.71 attacks/month from 2 attacks/month through days 1‒90 and remained ≤1 attack/month.

Finally, in 85 patients reporting 90-day baseline of 10 or more attacks before using berotralstat, the median baseline attack fell to 1.58 attacks/month from >3.33 attacks/month through day 90 and remained low.