Once-daily, oral berotralstat may rapidly and substantially reduce hereditary angioedema attacks: Study

The reduction in attack rates was observed regardless of the severity of the disease, the history of prior prophylaxis or the patient's C1-inhibitor (C1-INH) level and function.

The findings were presented in five posters at the 2024 American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting, held at the Walter E. Washington Convention Center in Washington, D.C., from February 23-26, 2024. Three posters were cited in the announcement, which assessed real-world efficacy for those aged 12 years and up with hereditary angioedema.

“These additional analyses of real-world use of ORLADEYO show that any person living with HAE has the potential to experience a rapid, substantial and sustained reduction in their monthly attack rate with ORLADEYO," according to Jonathan Bernstein, M.D., professor of medicine, department of internal medicine, division of allergy & immunology at the University of Cincinnati and partner of the Bernstein Allergy Group and Bernstein Clinical Research Center.

"From patients who live with severe disease to well-controlled patients and those who have a history of being treated with other long-term prophylaxis that carries a therapeutic burden, these data demonstrate that once patients begin oral, once-daily ORLADEYO, they can experience attack control for their treatment."

Three posters highlight data collected through the sole-source pharmacy of BioCryst that show real-world effectiveness outcomes for patients aged 12 and above with HAE who initiated ORLADEYO in the United States. These analyses present the overall attack rate progression and attack rate progression stratified by severity (i.e., number of attacks at baseline), prior prophylaxis and C1-INH level and function.

“We are continuing to see strong disease control with ORLADEYO in the real world, including in patients with HAE who report differing baseline disease severities," Dr. Ryan Arnold, chief medical officer of BioCryst, said in a statement.

He added, "These findings further demonstrate that ORLADEYO can help maintain disease control in patients with lower baseline attack rates and further reduce attack rates in patients with more active disease. We continue to be encouraged by the consistent, building body of real-world evidence demonstrating the significant benefit that our oral, once-daily prophylactic therapy can provide to people living with HAE."

The first study was titled ‘Berotralstat Prophylaxis Reduces HAE Attack Rates Regardless of Baseline Attacks: Real-World Outcomes,’ in which the participants known to have C1-INH deficiency receiving long-term prophylaxis with berotralstat showed rapid and sustained reductions in their monthly rates of HAE attacks.

The researchers found a dip in the median rates of HAE below baseline in the first 90 days of treatment. They added that these rates continued to be consistently reduced over subsequent 90-day intervals for up to 18 months and that this occurred regardless of attack severity at the point of baseline.

In the analysis titled ‘Consistently Low Hereditary Angioedema Attack Rates with Berotralstat Regardless of Prior Prophylaxis: Real-World Outcomes,’ the researchers showed substantial reductions in HAE attacks among participants who had previously attempted to use other prophylactic therapies and then started berotralstat.

These reductions were sustained and observed irrespective of subjects’ previous treatments, such as subcutaneous C1-INH, lanadelumab, and androgens. The researchers also noted that participants given lanadelumab previously saw a decrease in median monthly attack rate from 1.00 at the point of baseline to 0.33 in the initial 90 days of treatment, and this rate stayed below baseline through days 451-540.

The second study, titled ‘Real-World Effectiveness of Berotralstat in HAE With and Without C1-Inhibitor Deficiency,’ led to results suggesting that participants with normal C1-INH levels and subjects showing deficiency in C1-INH reported monthly HAE attack rate reduced with the use of berotralstat. Specifically, the investigators found that the drug led to a substantial decrease in these rates which were sustained over time.

The participants' median attack rates among those with normal C1-INH dipped from 3.00 at the point of baseline to 1.00 on days 1-90. They also revealed that participants with C1-INH deficiency saw rates go from 1.33 to 0.50; the results persisted through days 451-540.

“From patients who live with severe disease to well-controlled patients and those who have a history of being treated with other long-term prophylaxis that carries a therapeutic burden, these data show that once patients begin oral, once-daily (berotralstat), they can experience attack control throughout their treatment,” Bernstein concluded.