Once-Daily Berotralstat Treatment for HAE Consistently Decreases Attack Occurrences


These new data from BioCryst, presented at AAAAI, suggest that patients treated with berotralstat may see substantial decreases in HAE attacks.

Jonathan Bernstein, MD

Credit: Bernstein Allergy Group

Jonathan Bernstein, MD

Credit: Bernstein Allergy Group

BioCryst Pharmaceuticals, Inc. announced that once-daily, oral berotralstat (Orladeyo) treatment may lead to fast, considerable, and consistent hereditary angioedema (HAE) attack decreases over a course of 18 months.1 These positive results for berotralstat were noted by the investigators regardless of the condition’s severity, of a prior prophylaxis regimen, or of patients’ C1-inhibitor (C1-INH) levels.

These findings, drawn from several different analyses, were presented at the 2024 American Academy of Allergy, Asthma & Immunology (AAAAI) annual conference in Washington, DC. There were 3 posters cited in the announcement which had assessed real-world efficacy for those aged 12 years and up with HAE.

The investigators of each of these analyses looked into the overall progression of HAE attack rates, stratifying the condition’s progression based on prior prophylactic measures, severity, and C1-INH levels as well as function.

“These additional analyses of real-world use of (berotralstat) show that any person living with HAE has the potential to experience a rapid, substantial and sustained reduction in their monthly attack rate with (berotralstat),” Jonathan Bernstein, MD, professor of medicine at the University of Cincinnati’s division of allergy & immunology, said in a statement.

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

The investigators involved in this analysis noted that median rates of HAE dipped below baseline in the first 90 days of treatment. They added that these rates continued to be consistently lower 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,’ substantial reductions in HAE attacks were seen among participants who had previously attempted to use other prophylactic therapies and then started berotralstat.

The study’s research team also found that these reductions were sustained and observed regardless of subjects’ previous treatments such as subcutaneous C1-INH, lanadelumab, and androgens. They 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 indicating that subjects with normal C1-INH levels and subjects showing deficiency in C1-INH reported monthly HAE attack rate decreases upon their use of berotralstat. Specifically, the investigators found that the drug led to substantial reductions in these rates which were sustained over the course of time.

The team added that subjects’ median attack rates among those with normal C1-INH were shown to have dipped from 3.00 at the point of baseline to 1.00 at days 1-90. They also found that participants with C1-INH deficiency saw rates go from 1.33 to 0.50, with these results persisting 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 carry a therapeutic burden, these data demonstrate that once patients begin oral, once-daily (berotralstat), they can experience attack control over the duration of their treatment,” Bernstein concluded.

The announcement of these findings on berotralstat also included 2 additional posters which presented real-world study findings on those aged 12 years and older with HAE in the country of France. One of these 2 analyses was the ongoing prospective MATCH study (Monitoring HAE Treatment Compliance by the community pHarmacist) and the other was an observational study known as BeroLife.

The first of these 2 studies, titled ‘Evaluation of Adherence to Berotralstat in Patients with Hereditary Angioedema: A Prospective Survey in Community Pharmacies,’ was the MATCH trial which looked at individuals given monthly follow-up meeting with a pharmacist for a half of a year. These findings showed an association between adherence to berotralstat and its efficacy.

The investigators did also find, however, no observed link between adherence to treatment and the incidence of adverse events. They added that only 12.8 percent of participants in the study discontinued their course of treatment during the team’s research, noting no serious drug-related adverse events.

The findings from the second of these 2 analyses, titled ‘Assessment of the Tolerability and Effectiveness of Berotralstat for Long-term Prophylaxis in Hereditary Angioedema: BeroLife Study Interim Analysis,’ suggested that long-term prophylaxis with berotralstat was shown to be generally well-tolerated.

The research team noted that the drug’s safety profile was consistent with prior clinical data, given that only 15.6 percent of the participants had drug-related treatment-emergent adverse events. Additionally, the team found that less than 10 percent of the subjects discontinued treatment due to such events.

Overall, the investigators found a decrease in HAE attack rates had been observed among study participants, adding that most of such patients had received previous long-term prophylaxis. These findings aligned with data from the drug’s clinical trials, and the final data from this particular analysis are anticipated later in 2024.

In research presented during the 2023 AAAAI Annual Meeting, the early treatment of HAE symptoms, or prodromes, had been acknowledged as a means to prevent acute attacks. The implementation of transcriptomic analysis for clinicians’ understanding of the mechanisms underlying HAE had also been highlighted.2

The new findings on berotralstat may contribute to such research, as last year’s data may allow clinicians to address HAE prior to an attack and the new analyses highlighted by BioCryst could contribute to clinicians’ armamentarium for addressing the condition after attacks take place.


  1. BioCryst Presents New Real-world Data Showing Rapid, Substantial and Sustained HAE Attack Rate Reductions After Beginning ORLADEYO® (berotralstat) Treatment. BioCryst Pharmaceuticals, Inc. February 23, 2024. https://www.globenewswire.com/news-release/2024/02/23/2834384/29446/en/BioCryst-Presents-New-Real-world-Data-Showing-Rapid-Substantial-and-Sustained-HAE-Attack-Rate-Reductions-After-Beginning-ORLADEYO-berotralstat-Treatment.html. Date accessed: February 26, 2024.
  2. Grossi G. Debajyoti Ghosh, PhD: Potential Benefits of Treating Hereditary Angioedema Early Symptoms. HCPLive. February 27, 2023. https://www.hcplive.com/view/debajyoti-ghosh-potential-benefits-treating-hereditary-angioedema-early-symptoms. Date accessed: February 27, 2024.
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