BioCryst Presents New Data on the Long-term Efficacy and Safety of ORLADEYO® (berotralstat) Across all Ages at EAACI
- 86% reduction in attacks requiring professional care in pediatric patients
- Sustained reduction in HAE attacks for up to 48 weeks in pediatric patients
- Significant reduction in monthly attacks from 1.0 to 0.44 after six months in patients aged >12
- 60% of patients achieved Minimal Clinically Important Difference in quality of life scores
- Consistent safety profile across all age groups with minimal side effects
- None.
Insights
BioCryst's ORLADEYO shows strong efficacy across age groups with 86% reduction in pediatric HAE attacks, supporting its market position.
The new data presented for ORLADEYO (berotralstat) significantly strengthens BioCryst's market position in the hereditary angioedema (HAE) space. The 86% reduction in attacks requiring professional care in pediatric patients is particularly compelling, as it expands the drug's potential patient population beyond its current adolescent and adult approval. The sustained efficacy shown across multiple timepoints—up to 48 weeks in children and 24 months in the real-world Berolife study—addresses a critical aspect of chronic medication assessment that investors often scrutinize.
The quality of life improvements demonstrated in the pooled Phase 3 analysis provide valuable differentiation in a competitive market. With 60% of patients achieving clinically meaningful improvements in quality of life measures at week 24, ORLADEYO offers more than just attack reduction—it delivers functional benefits that could drive patient preference and adherence. This holistic impact on patient well-being, combined with the favorable safety profile and oral administration, positions ORLADEYO as a potentially preferred long-term prophylactic option.
The real-world French Berolife study results are particularly valuable as they validate the controlled clinical trial outcomes in a practical setting. The qualitative focus group findings, while limited in sample size (n=7), provide insights into patient preference factors that could influence prescribing patterns. The reported improvements in disease control with minimal side effects and reduced treatment burden could translate to higher persistence rates and expanded market share for BioCryst, especially as the company works to establish ORLADEYO as a first-line prophylactic treatment for HAE.
ORLADEYO shows robust, sustained HAE attack reduction across all age groups with significant quality of life improvements.
The APeX-P pediatric data represents a significant advancement in HAE management for younger patients. The 86% reduction in attacks requiring professional care is remarkable in this difficult-to-treat population. The weight-based dosing approach using both capsules (150mg) and granules (78-108mg) demonstrates thoughtful clinical development for pediatric applications, addressing practical administration challenges in children as young as 3 years old.
From a mechanistic perspective, the rapid onset of action—evident from the attack reduction in the first four weeks—suggests effective plasma kallikrein inhibition is achieved quickly and maintained consistently. The monthly attack rate reduction from 1.28 to 0.38 within the first month supports this pharmacodynamic efficiency. The durability of response, maintained through 48 weeks in pediatrics and up to 24 months in the Berolife adult cohort, indicates minimal tachyphylaxis or tolerance development.
The safety profile remains consistent with previous trials, with predominantly mild adverse events like nasopharyngitis and headache. This tolerability, combined with the oral administration route, addresses major compliance barriers associated with injectable prophylactic alternatives. The quality of life improvements across all four AE-QoL domains (functioning, fatigue/mood, fears/shame, and nutrition) reflect the comprehensive impact of attack reduction on patient experience. The increasing proportion of patients reaching clinically meaningful improvements over time suggests progressive adaptation and normalization of daily activities that were previously limited by attack anticipation. This multi-dimensional efficacy profile positions ORLADEYO as a clinically significant advancement in the long-term management of HAE across the age spectrum.
—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
INDICATION
ORLADEYO® (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 use
The 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 INFORMATION
An 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 (≥
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 <12 years of age have not been established.
There are insufficient data available to inform drug-related risks with ORLADEYO use in pregnancy. There are no data on the presence of berotralstat in human milk, its effects on the breastfed infant, or its effects on milk production.
To report SUSPECTED ADVERSE REACTIONS, contact BioCryst Pharmaceuticals, Inc. at 1-833-633-2279 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see full Prescribing Information.
About BioCryst Pharmaceuticals
BioCryst Pharmaceuticals is a global biotechnology company with a deep commitment to improving the lives of people living with hereditary angioedema and other rare diseases. BioCryst leverages its expertise in structure-guided drug design to develop first-in-class or best-in-class small-molecule and protein therapeutics to target difficult-to-treat diseases. BioCryst has commercialized ORLADEYO® (berotralstat), the first oral, once-daily plasma kallikrein inhibitor, and is advancing a pipeline of small-molecule and protein therapies. For more information, please visit www.biocryst.com or follow us on LinkedIn.
Forward-Looking Statements
This press release contains forward-looking statements, including statements relating to ORLADEYO safety, performance and effectiveness. These statements involve known and unknown risks, uncertainties and other factors which may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. These statements reflect our current views with respect to future events and are based on assumptions and are subject to risks and uncertainties. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Some of the factors that could affect the forward-looking statements contained herein include: BioCryst’s ability to successfully implement or maintain its commercialization plans for ORLADEYO; interim results of a clinical trial do not necessarily predict final results; the commercial viability of ORLADEYO, including its ability to achieve sustained market acceptance; the FDA or other applicable regulatory agency may require additional studies beyond the studies planned for products and product candidates, may not provide regulatory clearances which may result in delay of planned clinical trials, may impose certain restrictions, warnings, or other requirements on products and product candidates, may impose a clinical hold with respect to product candidates, or may withhold, delay, or withdraw market approval for products and product candidates; and BioCryst’s ability to successfully manage its growth and compete effectively. Please refer to the documents BioCryst files periodically with the Securities and Exchange Commission, specifically BioCryst’s most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K, which identify important factors that could cause the actual results to differ materially from those contained in BioCryst’s forward-looking statements.
BCRXW
Contact:
John Bluth
+1 919 859 7910
jbluth@biocryst.com
Niamh Lyons
+353 87 7745000
nlyons@biocryst.com
FAQ
What are the key findings from BioCryst's ORLADEYO studies presented at EAACI 2025?
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