Interim Data Support Long-term Safety of Orladeyo for HAE Attacks
The findings from an interim analysis of the open-label APeX-S trial also supported Orladeyo’s ability to reduce the frequency of HAE attacks, ease symptom burden, and improve patients’ quality of life, in line with those of previous studies.
The data were reported in a study, “Long-term safety and effectiveness of berotralstat for hereditary angioedema: The open-label APeX-S study,” published in the journal Clinical and Translational Allergy.
Developed by BioCryst Pharmaceuticals, Orladeyo is an oral small molecule that has been approved as a preventive treatment for HAE in the U.S., the European Union, the U.K., and Japan. The medication is designed to prevent the levels of bradykinin, an inflammatory molecule that drives swelling in HAE, from rising too high.
BioCryst is sponsoring an open-label Phase 2/3 trial called APeX-S (NCT03472040) to assess the long-term safety and efficacy of Orladeyo in HAE patients, 12 and older.
In the new study, a team led by researchers at the company presented data from a pre-planned interim analysis of the trial.
In APeX-S, 227 participants were treated with Orladeyo, including 127 who received the medication at a daily dose of 150 mg, and 100 who received a lower daily dose of 110 mg.
The two groups were largely similar in terms of demographics: about two-thirds were female, more than 80% were white, and about 10% were Asian. The high-dose group was older, by about five years on average. At the time of this analysis, the median duration of treatment was slightly less than a year in both groups.
Overall, half of the participants experienced at least one medication-related adverse event, or side effect. The most common, in both dose groups, were abdominal pain (9.7%), diarrhea (7%), and nausea (6.2%). Most of these events were mild or moderate in intensity.
Three participants experienced severe adverse events that were deemed to be related to Orladeyo. One showed signs of abnormal liver function, another had elevated levels of liver enzymes accompanied by gastroenteritis (digestive system inflammation), and a third participant experienced severe abdominal pain. All three of these events eventually resolved after treatment was stopped.
Laboratory testing showed abnormally high levels of alanine aminotransferase — a marker of liver damage and inflammation — in 6% of participants. This was most common in the first month of treatment and tended to affect people who had previously been treated with androgens (male hormones).
A total of 25% of participants discontinued the study. The most cited reasons for study discontinuation included a perceived lack of efficacy (12%) and adverse events or laboratory abnormalities (8%).
Overall, the safety profile of Orladeyo in this analysis is similar to what has been seen in prior studies, the researchers said.
“This planned data analysis demonstrated that long-term treatment with once-daily oral berotralstat [Orladeyo] 150 or 110 mg was well tolerated … with no new safety signals observed,” they wrote.
Among trial participants who were treated with Orladeyo for up to 48 weeks (about a year), rates of HAE attacks declined throughout the treatment period. By one year of treatment, the median attack rate in both dose groups was zero attacks per month, meaning that most participants were not experiencing HAE attacks on any given month.
Among the attacks that did occur, over three-quarters were described by patients as being “negligible, mild, or moderate in severity,” according to researchers.
Statistical analyses also indicated that Orladeyo decreased the median number of days patients had to deal with angioedema symptoms to less than a month per year in both dose groups.
Clinically meaningful improvements in quality of life were also reported among participants treated for a year.
“Effectiveness results support the durability and robustness of berotralstat [Orladeyo] as prophylactic [preventive] therapy in patients with HAE,” researchers wrote. “This study remains ongoing to further assess long-term safety and effectiveness of berotralstat [Orladeyo] 150 mg beyond 48 weeks of therapy.”