BioCryst Presents New Real-world Evidence Showing Significant and Sustained Reductions in HAE Attack Rates in Adolescents and People with Severe HAE Following Initiation of ORLADEYO® (berotralstat)

Rhea-AI Summary

BioCryst Pharmaceuticals (BCRX) presented new real-world evidence demonstrating the effectiveness of ORLADEYO® (berotralstat) in treating Hereditary Angioedema (HAE) at ISPOR 2025. The study analyzed data from December 2020 to January 2024, focusing on two patient groups: 1. Severe HAE Patients (56 patients): - Baseline: 7.78-8.23 attacks/month - After ORLADEYO: 1.24-1.90 attacks/month - At 18 months: 6.43 fewer attacks/month 2. Adolescent Patients (99 patients aged 12-17): - Baseline: 2.07-2.30 attacks/month - After ORLADEYO: 0.36-0.76 attacks/month - At 18 months: 1.85 fewer attacks/month The results demonstrate significant and sustained reductions in HAE attack rates through 18 months of treatment, showing ORLADEYO's effectiveness across different patient populations.

Positive

• Significant reduction in HAE attacks for severe patients from 7.78-8.23 to 1.24-1.90 attacks per month
• Strong efficacy in adolescents with reduction from 2.07-2.30 to 0.36-0.76 attacks per month
• Sustained positive results through 18 months of treatment
• Large patient sample size with 99 adolescents and 56 severe HAE patients

Negative

• None.

Insights

Biotechnology Clinical Research Analyst

Real-world data shows ORLADEYO significantly reduces HAE attacks in severe patients and adolescents, strengthening market position against competitors.

BioCryst's latest real-world evidence for ORLADEYO demonstrates impressive clinical efficacy that should positively impact the drug's commercial trajectory. The data shows 6.43 fewer monthly attacks in severe HAE patients and 1.85 fewer monthly attacks in adolescents at the 18-month mark – representing approximately 80% and 78% reductions from baseline, respectively.

This data is commercially significant for several reasons. First, real-world effectiveness often carries more weight with prescribers than controlled clinical trials, as it reflects performance in typical practice settings. Second, the sustained efficacy over 18 months addresses a critical concern about long-term treatment durability.

The results in adolescents (ages 12-17) are particularly valuable as they support ORLADEYO's use across a broader age spectrum, potentially capturing patients earlier in their treatment journey. Similarly, the strong performance in severe HAE patients (those with ≥8 attacks/month) demonstrates efficacy in a difficult-to-treat population that likely requires more intensive healthcare resources.

From a competitive standpoint, ORLADEYO's oral administration continues to differentiate it from injectable prophylactic alternatives. This convenience factor, now reinforced with robust long-term efficacy data, strengthens BioCryst's market position against therapies from competitors like Takeda and CSL Behring.

The timing of this data presentation at ISPOR – a pharmacoeconomics conference – suggests BioCryst is building a stronger value proposition for payers, potentially supporting favorable reimbursement decisions and reducing barriers to prescription.

Healthcare Financial Analyst

New ORLADEYO data reinforces commercial strength for BioCryst's lead revenue driver, supporting continued market penetration and sales growth.

This real-world evidence meaningfully strengthens ORLADEYO's commercial profile as BioCryst's flagship product. The data in severe HAE patients (≥8 attacks/month) is particularly valuable from a financial perspective, as these high-need patients likely represent premium reimbursement opportunities and high persistence rates.

ORLADEYO generated $325.6 million in revenue in 2023, accounting for nearly all of BioCryst's product revenue. These positive real-world outcomes should help drive further market penetration, especially since the data specifically addresses two valuable market segments:

• Adolescent patients (ages 12-17), representing a long-term treatment population
• Severe disease patients, who likely have higher healthcare utilization costs

The sustained efficacy over 18 months is commercially critical as it suggests strong patient retention – essential for maintaining recurring revenue for chronic therapies. Higher persistence translates directly to improved lifetime value per patient.

From a market positioning standpoint, this reinforces ORLADEYO's competitive profile against injectable alternatives. The oral administration remains a compelling differentiator that, combined with this effectiveness data, should support continued prescription growth and potential formulary improvements.

BioCryst specifically presented these findings at ISPOR – a conference focused on health economics and outcomes research – indicating the company is building economic justification for payers. This strategy typically supports improved access and reimbursement, reducing barriers to prescription and supporting revenue growth.

While not discussed in the release, this data may also help expand ORLADEYO's international market potential, as real-world effectiveness data often influences reimbursement decisions in markets with nationalized healthcare systems.

RESEARCH TRIANGLE PARK, N.C., May 16, 2025 (GLOBE NEWSWIRE) -- BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) today announced new real-world evidence on the use of oral, once-daily ORLADEYO^® (berotralstat) in adolescents and people with severe HAE showing significant and sustained reductions in HAE attack rates through 18 months of follow-up after beginning treatment with ORLADEYO in both patient populations.

The real-world evidence was presented in two posters at the 2025 International Society for Pharmacoeconomics and Outcomes Research conference (ISPOR), which is being held in Montreal from May 13-16, 2025.

“The outcomes detailed in these posters show how ORLADEYO is making a difference for people living with HAE, in particular those with very severe disease and those who are adolescents. These two groups experienced far fewer attacks per month compared to baseline after starting ORLADEYO. These kinds of real-world results should give physicians as well as their HAE patients the additional confidence to improve control of their attacks,” said Dr. Raffi Tachdjian, associate clinical professor of medicine & pediatrics, division of allergy & clinical immunology, David Geffen School of Medicine, University of California Los Angeles.

Significant and sustained reductions in attack rates after ORLADEYO initiation

The results presented in two posters at ISPOR 2025 were from a retrospective pre-post study using outcomes collected from BioCryst’s sole-source pharmacy from December 15, 2020, to January 8, 2024.

The poster “Real-World Hereditary Angioedema Attack Rates Before and After Berotralstat Initiation Among Patients with C1 Inhibitor Deficiency (Type I/II) and ≥8 Attacks/month” (#PCR182) detailed findings from 56 U.S. patients with HAE with C1-inhibitor deficiency (HAE-C1-INH) who received ORLADEYO.

• Patients experienced significantly lower HAE attack rates while on ORLADEYO in each 90-day follow-up period (1.24-1.90 attacks/month) compared to baseline (7.78-8.23 attacks/month).
• Patients experienced significantly fewer HAE attacks per month following ORLADEYO initiation during every 90-day follow-up period relative to baseline, including:
  • 6.25 fewer attacks/month (95 percent confidence period (CI): [5.63, 6.87]; p<0.001) at 12 months (days 271-360)
  • 6.43 fewer attacks/month (95 percent CI: [5.78, 7.09]; p<0.001) at 18 months (days 451-540)

The poster “Real-World Hereditary Angioedema Attack Rates Before and After Berotralstat Initiation Among Adolescents” (#PCR132) highlighted outcomes reported from 99 U.S. patients with HAE aged 12-17 years who received ORLADEYO.

• Patients had significantly lower HAE attack rates while on ORLADEYO during each 90-day follow-up period (0.36-0.76 attacks/month) compared to the mean baseline rate (2.07-2.30 attacks/month).
• Compared to baseline, adolescents experienced statistically significant and sustained reductions in HAE attack rates after ORLADEYO initiation during each 90-day follow-up period, including:
  • 1.56 fewer attacks/month (95 percent CI: [0.89, 2.23]; p<0.001) at 12 months (days 271-360)
  • 1.85 fewer attacks/month (95 percent CI: [1.12, 2.58]; p<0.001) at 18 months (days 451-540)

“We continue to generate evidence from real-world use of our oral, once-daily prophylactic therapy for HAE that supports its effectiveness in a wide range of people with HAE. Here, we show that ORLADEYO is having a positive impact on attack reduction for younger people and those with severe disease. These additional findings further underscore that ORLADEYO works well for many patients with HAE, regardless of their attack severity, age or other aspects,” said Dr. Donald S. Fong, chief medical officer of BioCryst.

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 (≥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 <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 regarding future results, performance or achievements and statements relating to ORLADEYO 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; 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

FAQ

What are the results of ORLADEYO in treating severe HAE patients according to BioCryst's 2025 study?

According to the study, severe HAE patients experienced a reduction from 7.78-8.23 attacks per month at baseline to 1.24-1.90 attacks per month after ORLADEYO treatment, with 6.43 fewer attacks per month at 18 months.

How effective is ORLADEYO in treating adolescent HAE patients aged 12-17?

The study showed adolescent HAE patients experienced a reduction from 2.07-2.30 attacks per month at baseline to 0.36-0.76 attacks per month after ORLADEYO treatment, with 1.85 fewer attacks per month at 18 months.

What is the duration and size of BioCryst's (BCRX) ORLADEYO real-world study?

The study analyzed data from December 15, 2020, to January 8, 2024, including 56 severe HAE patients and 99 adolescent patients aged 12-17 years.

Does ORLADEYO maintain its effectiveness over time in treating HAE?

Yes, the study demonstrated that ORLADEYO maintains significant and sustained reductions in HAE attack rates through 18 months of follow-up in both severe and adolescent patient populations.