Rifampin

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 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 <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 7910jbluth@biocryst.com

结核病是当今世界上严重威胁人类生命健康的重大传染性疾病，由病原体结核分枝杆菌感染引起。当前抗结核治疗手段非常有限，主要依靠异烟肼、利福平、乙胺丁醇、吡嗪酰胺等一线抗结核药物联合用药进行治疗。但结核耐药问题始终无法克服，还面临日益加重的严峻形势，给结核病防治带来了极大的挑战。除了药物靶点突变引起耐药以外，药物外排泵（包括ABC家族转运体）是导致耐药的重要原因之一。然而，结核病药物外排泵的发现多为间接证据，尤其缺少分子层面的直接证据。近日，上海科技大学免疫化学研究所李俊/清华大学饶子和等团队在《自然-通讯》（Nature Communications）在线发表了题为“Structure and mechanism of a mycobacterial isoniazid efflux pump MsRv1273c/72c with a degenerate nucleotide-binding site”的研究论文，在国际上率先发现并鉴定分枝杆菌异源二体型ABC转运体MsRv1273c/72c是一线抗结核药物异烟肼的外排泵。此外，研究还揭示了一种由退化型ATP结合位点和不对称构象介导的底物转运新机制。这一研究不仅阐明了一种结核病耐药的关键途径，更重要的是为结核病治疗提供了新的药物靶标，对开发新型抗结核药物和解决全球结核病耐药性问题具有重要科学意义和临床研究价值。研究人员针对结核分枝杆菌的ABC家族转运体Rv1273c/72c及其耻垢杆菌同源蛋白展开了研究，证明MsRv1273c和MsRv1272c形成异源二体形式的完整转运体，并且含有一个退化型的ATP结合位点。接着，研究人员通过体外脂质体转运实验和质谱分析首次从分子水平证明该转运体是一个异烟肼药物外排泵并且具有浓度依赖关系，进一步通过敲除回补和细菌生长实验证明MsRv1273c/72c的存在确实降低了分枝杆菌对异烟肼的敏感性，导致了细菌对异烟肼耐药。研究人员利用冷冻电镜解析了MsRv1273c/72c处于不同状态下的一系列结构，发现该异源二体转运体存在不对称性，特别是在MsRv1272c中多出了额外的N端extending loop和胞外侧helical hairpin结构，可能用于帮助底物进入跨膜区的中央空腔和从中央空腔释放至周质侧。本研究首次捕获到了三种不对称型构象，这些构象从未在其他类似的异源二体ABC转运体的研究工作被报道。▲分枝杆菌MsRv1273c/72c的三种不对称中间态结构（左）、异烟肼转运实验（中上），敲除/回补-生长实验（右上），和底物转运机制图（右下）（图片来源：参考资料[1]）结构分析表明，其胞内可溶区的核苷酸结合结构域（NBD）均呈现部分二聚化，两个NBD只在退化型ATP结合位点处关闭，而在另一个正常的ATP结合位点处则不同程度打开。由此，这些构象代表了转运体处于两个NBD打开（中央空腔向内开口状态）和完全关闭（中央空腔内外同时闭合或者向外开口状态）之间的中间状态。这些中间态是状态转换所必须的，其中，MsRv1272c的NBD中的D-WalkerB loop和X-signature loop通过构象变化可影响ATP在两个核苷酸结合位点的结合。该转运体通过NBD在退化型ATP结合位点的部分二聚化，来调控和协调两个ATP结合位点的功能活性，进而介导了整个底物转运过程。综上，本研究揭示了MsRv1273c/72c的由退化型ATP结合位点和不对称构象介导的一种底物转运新机制，这与同源二体型ABC转运体（含有两个正常活性的ATP结合位点）显著不同，为深入理解其他含有退化型ATP结合位点的异源二体ABC转运体（比如，半数的人源异源二体ABC转运体都含有退化型ATP结合位点）提供了重要参考和启示，增加了对ABC转运体家族结构和机制多样性的认识。Rv1273c/72c有望成为一个有价值的药物新靶点，通过开发靶向抑制剂并与异烟肼的联合使用来提高异烟肼的治疗效果，从而降低异烟肼耐药的发生率。MsRv1273c/72c作为一个新发现的异烟肼药物外排泵，为研究和解决异烟肼耐药问题提供了新的思路。上海科技大学博士毕业生于菁和博士生兰宇辉为本文共同第一作者，上海科技大学为第一完成单位。来源：上海科技大学原始论文：[1] Neural-activity-regulated and glia-mediated control of brain lymphatic development. Cell (2025). https://doi.org/10.1158/0008-5472.CAN-24-2289免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。更多推荐点个“在看”再走吧~