Berotralstat Hydrochloride

—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 (≥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 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 Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

–Real-world data highlight significant challenges with LTP adherence, and ongoing reliance on on-demand medications– –In KONFIDENT-S, oral sebetralstat delivered rapid, consistent relief for breakthrough attacks, regardless of long-term prophylaxis mechanism of action– CAMBRIDGE, Mass. & SALISBURY, England--(BUSINESS WIRE)--Jun. 16, 2025-- KalVista Pharmaceuticals, Inc. (Nasdaq: KALV) today announced the presentation of new data at the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2025 in Glasgow, United Kingdom that underscores the critical role of effective on-demand (OD) treatment for HAE attacks among patients receiving long-term prophylaxis (LTP). Sebetralstat for Treatment of HAE Attacks in Patients Receiving Berotralstat, Lanadelumab, or C1 Inhibitor for Long-term Prophylaxis: Interim Analysis from KONFIDENT-S was presented by Marc A. Riedl, MD, Professor of Medicine and Clinical Director of the US Hereditary Angioedema Association Center at the University of California, San Diego. The KONFIDENT-S interim analysis, involving 35 participants receiving berotralstat, lanadelumab, or C1 inhibitor (C1-INH), treated 382 attacks with sebetralstat Median time to treatment was 6 minutes overall, ranging from 1 minute (C1-INH) to 20 minutes (berotralstat) One-third of attacks were still mild at time of sebetralstat use Median time to beginning of symptom relief was 1.3 hours "Even with advancements in HAE long-term prophylactic treatments, attacks still occur, highlighting the critical need for easily administered, fast-acting, effective on-demand options," said Dr. Riedl. "These data from KONFIDENT-S show the promise of sebetralstat as an effective oral on-demand option that can complement all major long-term prophylaxis treatments, including those acting through plasma kallikrein inhibition, like lanadelumab and berotralstat.” Adherence to Long-Term Prophylaxis for Hereditary Angioedema and the Impact on On-demand Treatment Claims in the US was presented by Daniel Soteres, MD, MPH, Asthma and Allergy Associates and Research Center, Colorado. Less than half (44%) of HAE patients using LTP were adherent based on refill data over 12 months No reduction in OD claims was observed in non-adherent patients (18 pre- and post-LTP; p=0.769) Over 12 months, greater than 20% discontinued their LTP, while 17% switched LTP "The real-world data suggest that despite the effectiveness of long-term prophylactic therapies in clinical trials, maintaining adherence may be a significant hurdle for many HAE patients," said Dr. Soteres. "Refill gaps correlated with a greater number of on-demand treatment claims, indicating that patients may be experiencing more frequent attacks than expected. This underscores the importance of actively discussing LTP adherence with patients and having a reliable, efficacious on-demand treatment to manage breakthrough attacks.” “These data reinforce what we hear from patients and clinicians on an ongoing basis; long-term prophylaxis plays an essential role in HAE management, but it’s not the full story,” said Paul Audhya, M.D., MBA, Chief Medical Officer of KalVista. “Attacks still occur, and adherence remains a real-world challenge. Sebetralstat is designed to meet this need: a rapid, reliable oral treatment that empowers patients to act the moment symptoms begin, regardless of their background therapy.” Links to all presentations can be found on the KalVista website under Publications. About Sebetralstat Sebetralstat is an investigational, novel oral plasma kallikrein inhibitor for the treatment of hereditary angioedema (HAE). We have filed multiple regulatory applications seeking approval of sebetralstat as the first oral, on-demand treatment for HAE in individuals aged 12 and older, with ongoing studies exploring its use in children aged 2 to 11. If approved, sebetralstat has the potential to become the foundational therapy for HAE management worldwide. About Hereditary Angioedema Hereditary angioedema (HAE) is a rare genetic disease resulting in deficiency or dysfunction in the C1 esterase inhibitor (C1INH) protein and subsequent uncontrolled activation of the kallikrein-kinin system. People living with HAE experience painful and debilitating attacks of tissue swelling in various locations of the body that can be life-threatening depending on the area affected. All currently approved on-demand treatment options require either intravenous or subcutaneous administration. About KalVista Pharmaceuticals, Inc. KalVista Pharmaceuticals, Inc., is a global biopharmaceutical company dedicated to developing and delivering life-changing oral therapies for individuals affected by rare diseases with significant unmet needs. Our lead investigational product is sebetralstat, a novel, oral, on-demand treatment for hereditary angioedema (HAE). Sebetralstat is under regulatory review by the U.S. FDA. In addition, we have completed Marketing Authorization Applications for sebetralstat to the European Medicines Agency and multiple other global regulatory authorities. For more information about KalVista, please visit www.kalvista.com or follow us on social media at @KalVista and LinkedIn. Forward-Looking Statements This press release contains "forward-looking" statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as: "anticipate," "intend," "plan," "goal," "seek," "believe," "project," "estimate," "expect," "strategy," "future," "likely," "may," "should," "will" and similar references to future periods. These statements are subject to numerous risks and uncertainties that could cause actual results to differ materially from what we expect. Examples of forward-looking statements include, among others, timing or outcomes of communications with the FDA, our expectations about safety and efficacy of our product candidates and timing of clinical trials and its results, our ability to commence clinical studies or complete ongoing clinical studies, including our KONFIDENT-S and KONFIDENT-KID trials, and to obtain regulatory approvals for sebetralstat and other candidates in development, the success of any efforts to commercialize sebetralstat, the ability of sebetralstat and other candidates in development to treat HAE or other diseases, and the future progress and potential success of our oral Factor XIIa program. Further information on potential risk factors that could affect our business and financial results are detailed in our filings with the Securities and Exchange Commission, including in our annual report on Form 10-K for the year ended April 30, 2024, our quarterly reports on Form 10-Q, and our other reports that we may make from time to time with the Securities and Exchange Commission. We undertake no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise. View source version on businesswire.com: https://www.businesswire.com/news/home/20250616564483/en/ Ryan Baker Head, Investor Relations (617) 771-5001 ryan.baker@kalvista.com Molly Cameron Director, Corporate Communications (978) 339-3378 molly.cameron@kalvista.com Source: KalVista Pharmaceuticals, Inc.