BioCryst Presents New Data on the Long-term Efficacy and Safety of ORLADEYO® (berotralstat) Across all Ages at EAACI
—Data across pediatric, adolescent, and adult populations demonstrate sustained reductions in HAE attacks and consistent safety profile—
—Patients report improved quality of life and daily functioning with ORLADEYO—
RESEARCH TRIANGLE PARK, N.C., June 16, 2025 (GLOBE NEWSWIRE) -- BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) today announced new data on the long-term efficacy and safety of ORLADEYO® (berotralstat) for the prophylactic treatment of hereditary angioedema (HAE) in patients across all age groups.
“These data from both clinical trials and real-world settings continue to strengthen the evidence that ORLADEYO is an effective and well-tolerated long-term prophylactic treatment for HAE. Importantly, patients report not only fewer and less severe attacks, but also meaningful improvements in daily functioning and emotional well-being. This contributes to the growing body of evidence supporting the use of ORLADEYO as a long-term prophylactic option for adolescents and adults living with HAE,” said Helen Thackray, chief research and development officer of BioCryst.
The following four studies were presented at the European Academy of Allergy and Clinical Immunology (EAACI) meeting in Glasgow, United Kingdom, from June 13 to 16, 2025.
Berotralstat Use Reduced Number of HAE Attacks Requiring Treatment or Professional Care in Pediatric Patients: Interim Results from APeX-P
The ongoing open-label APeX-P study is evaluating the pharmacokinetic, safety, and effectiveness of berotralstat in children aged 2 to 11 years with HAE. Patients were enrolled into four weight-based cohorts. Cohort 1 received a 150 mg capsule once daily; cohorts 2-4 received once-daily oral granule doses of 108 mg, 96 mg and 78 mg, respectively.
The median age was 8 years (range: 3–11), with disease onset typically between ages 2–6 years. All patients received standard of care (SOC) treatment for 12 weeks prior to the study.
Key results
- Eighty-six percent reduction in attacks requiring professional care: attacks dropped from 22 during the 12-week SOC period to three following 12 weeks of berotralstat treatment
- Early/rapid and sustained reduction in the rate of HAE attacks requiring on-demand treatment
- Mean (SEM) adjusted monthly attack rate decreased from 1.28 (0.25) during SOC to 0.38 (0.13) from day one to week four of berotralstat treatment
- Sustained reduction for up to 48 weeks of follow-up
- Berotralstat was well tolerated across all cohorts; the most common treatment-emergent adverse events were nasopharyngitis, upper respiratory tract infection, and headache.
Assessment of the Effectiveness and Tolerability of Berotralstat for Long-term Prophylaxis in Hereditary Angioedema: Findings from the Berolife Study
The Berolife study is an open-label observational study in France which assessed the real-world tolerability and effectiveness of oral once-daily berotralstat (150 mg) in patients with HAE aged >12 years. A total of 82 patients were enrolled, with a mean (SD) age of 40.0 (17.5) years. The mean (SD) baseline attack rate was 1.1 (1.0) attacks per month (median: 0.83), based on the six months prior to enrollment.
Key results
- Significant reduction in monthly HAE attacks was observed at six months (in patients with follow-up data (n=37))
- Median monthly attack rate decreased from 1.0 to 0.44 attacks after six months of berotralstat treatment
- Sustained reductions in attack frequency maintained at 12, 18, and 24 months
- Berotralstat was well tolerated throughout the study period
- Adverse events were consistent with previous clinical trial data
Impact of Berotralstat on Quality of Life in Patients with Hereditary Angioedema
This analysis assessed the impact of berotralstat on patient-reported quality of life (QoL) outcomes compared to placebo, using pooled data from previous Phase 3 APeX-2 and APeX-J clinical trials which showed that once-daily berotralstat 150 mg significantly reduced the frequency of HAE attacks. This QoL assessment was measured using the validated Angioedema Quality of Life Questionnaire (AE-QoL), which evaluates four key domains: functioning, fatigue/mood, fears/shame, and nutrition.
Key results
- Significant improvements in AE-QoL total and domain scores were observed with berotralstat versus placebo at week 24
- Benefits sustained through week 96, indicating lasting improvement in daily life
- At week 24, 60 percent of patients receiving berotralstat achieved the Minimal Clinically Important Difference (MCID) in AE-QoL total score, compared to 52.4 percent in the placebo group
- Over time, the proportion of patients reaching MCID increased in the berotralstat cohort, suggesting progressive and cumulative improvements in QoL alongside reductions in HAE attack frequency
Patients With HAE Report Positive Perceptions Following Berotralstat Treatment: Results from a Focus Group
This qualitative study explored patient experiences with HAE, including their care journey and perceptions of treatment with berotralstat. Focus groups were conducted to gain insight into the real-world impact of berotralstat on patients' daily lives. Seven patients from France, aged 20-70 years, participated in the focus groups. All had been treated with berotralstat for at least six months, with a median age at HAE diagnosis of 28 years. Prior to starting berotralstat, the majority of participants (71 percent) had switched from previous treatments due to long-term tolerability concerns and guidance from health authorities.
Key findings
- Participants reported notable improvements in disease control, including reduced frequency and severity of HAE attacks
- Minimal side effects were observed
- Berotralstat was described as less burdensome and easier to incorporate into daily routines compared to previous therapies
- Improved disease management was associated with reduced psychological distress and a greater sense of normalcy, contributing to enhanced quality of life
About ORLADEYO® (berotralstat)ORLADEYO® (berotralstat) is the first and only oral therapy designed specifically to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years and older. One capsule of ORLADEYO per day works to prevent HAE attacks by decreasing the activity of plasma kallikrein.
U.S. Indication and Important Safety Information
INDICATIONORLADEYO® (berotralstat) is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 12 years and older.
Limitations of useThe safety and effectiveness of ORLADEYO for the treatment of acute HAE attacks have not been established. ORLADEYO should not be used for the treatment of acute HAE attacks. Additional doses or dosages of ORLADEYO higher than 150 mg once daily are not recommended due to the potential for QT prolongation.
IMPORTANT SAFETY INFORMATIONAn increase in QT prolongation was observed at dosages higher than the recommended 150 mg once-daily dosage and was concentration dependent.
The most common adverse reactions (≥10% and higher than placebo) in patients receiving ORLADEYO were abdominal pain, vomiting, diarrhea, back pain, and gastroesophageal reflux disease.
A reduced dosage of 110 mg taken orally once daily with food is recommended in patients with moderate or severe hepatic impairment (Child-Pugh B or C).
Berotralstat is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein. P-gp inducers (eg, rifampin, St. John’s wort) may decrease berotralstat plasma concentration, leading to reduced efficacy of ORLADEYO. The use of P-gp inducers is not recommended with ORLADEYO.
ORLADEYO at a dose of 150 mg is a moderate inhibitor of CYP2D6 and CYP3A4. For concomitant medications with a narrow therapeutic index that are predominantly metabolized by CYP2D6 or CYP3A4, appropriate monitoring and dose titration is recommended. ORLADEYO at a dose of 300 mg is a P-gp inhibitor. Appropriate monitoring and dose titration is recommended for P-gp substrates (eg, digoxin) when coadministering with ORLADEYO.
The safety and effectiveness of ORLADEYO in pediatric patients
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