Orladeyo reduces swelling rates in severe HAE: Real-world data
Data also show treatment helps prevent attacks in adolescents
Treatment with the daily oral therapy Orladeyo (berotralstat) can effectively reduce swelling attack rates in people with hereditary angioedema (HAE) who experienced many such attacks before starting on the therapy, real-world data showed.
Additional real-world data indicated that Orladeyo is also effective for preventing swelling attacks in adolescents with HAE.
Biocryst Pharmaceuticals, the company that markets Orladeyo, presented the new analyses in a pair of posters at ISPOR 2025, the annual conference of ISPOR—The Professional Society for Health Economics and Outcomes Research, held May 13-16 in Montreal.
“We continue to generate evidence from real-world use of our oral, once-daily prophylactic therapy for HAE that supports its effectiveness in a wide range of people with HAE,” Donald S. Fong, MD, chief medical officer of Biocryst, said in a company press release. “Here, we show that ORLADEYO is having a positive impact on attack reduction for younger people and those with severe disease. These additional findings further underscore that ORLADEYO works well for many patients with HAE, regardless of their attack severity, age or other aspects.”
HAE is characterized by swelling attacks driven by the excessive production of a signaling molecule called bradykinin. The most common forms of HAE, types 1 and 2, are caused by mutations that impair the production or activity of C1 inhibitor, a protein that normally helps regulate bradykinin production.
Treatment shows effectiveness in trials
Orladeyo works to prevent HAE swelling attacks by inhibiting kallikrein, an enzyme that mediates bradykinin production. It is approved in the U.S. and several other countries as a prophylactic (preventive) treatment for HAE in patients ages 12 and older.
Clinical trials have shown that the therapy can reduce swelling attack rates in HAE patients, but trials are rigorously controlled and have strict enrollment criteria, so they don’t perfectly reflect outcomes from real-world use.
The new data show that Orladeyo can effectively lower the rate of HAE swelling attacks in real-world settings.
In a poster titled, “Real-World Hereditary Angioedema Attack Rates Before and After Berotralstat Initiation Among Patients With C1 Inhibitor Deficiency (Type I/II) and =8 Attacks Per Month,” researchers reported the outcomes of Orladeyo treatment when used in routine practice to treat people with HAE types 1 or 2 who had relatively severe disease.
The analysis covered 56 people with HAE, with a mean age of 41.3, most of whom were female (76.8%).
Prior to starting on Orladeyo, these patients had about eight swelling attacks each month. After a year on the therapy, they were having 6.25 fewer attacks each month, on average. This reduction in attack rates was similar after 1.5 years on Orladeyo.
“Patients with [at least] 8 monthly baseline attacks and C1-inhibitor deficiency reported significantly lower HAE attack rates after [Orladeyo] initiation,” the researchers wrote. “Treatment effectiveness was consistent and sustained through 18 months of follow-up.”
The other poster, “Real-World Hereditary Angioedema Attack Rates Before and After Berotralstat Initiation Among Adolescents,” covered the outcomes of 99 adolescents who were treated with Orladeyo. They had a mean age of 15.1, and roughly two-thirds were female (68.7%).
Prior to starting Orladeyo, the adolescents had slightly more than two swelling attacks each month, on average. After a year on the therapy, the average rate of swelling attacks dropped to fewer than one attack per month, and it remained low after 1.5 years on Orladeyo.
“Adolescents initiating [Orladeyo] reported statistically significant and sustained reductions in HAE attack rates through 18 months of follow-up,” the scientists wrote.
Raffi Tachdjian, MD, co-author of both posters and associate clinical professor of medicine and pediatrics at the University of California, Los Angeles, said the results “show how ORLADEYO is making a difference for people living with HAE, in particular those with very severe disease and those who are adolescents.”
“These two groups experienced far fewer attacks per month compared to baseline after starting ORLADEYO,” Tachdjian said. “These kinds of real-world results should give physicians as well as their HAE patients the additional confidence to improve control of their attacks.”
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