RESEARCH TRIANGLE PARK, N.C., Nov. 10, 2023 (GLOBE NEWSWIRE) -- BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) today announced new analyses of real-world use of oral, once-daily ORLADEYO® (berotralstat) leading to a reduction in monthly attack rates in patients with hereditary angioedema (HAE) who have normal C1-inhibitor (C1-INH) level and function..

RESEARCH TRIANGLE PARK，N.C.，2023年11月10日（GLOBE NEWSWIRE）-BioCryst Pharmaceuticals，Inc。（纳斯达克股票代码：BCRX）今天宣布对实际使用口服ORLADEYO®（berotralstat）的新分析，导致C1抑制剂（C1-INH）水平和功能正常的遗传性血管性水肿（HAE）患者每月发作率降低。。

“There is a significant unmet need among people who live with HAE with normal C1-INH, and identifying optimal treatments has been challenging for these patients. These real-world observations suggest ORLADEYO can have a meaningful impact on the lives of people who have HAE with normal C1-INH. We look forward to continuing to evaluate our oral, once-daily prophylaxis as a treatment option for this subpopulation,” said Dr.

“患有正常C1-INH的HAE患者存在显着未满足的需求，并且确定最佳治疗方法对这些患者具有挑战性。这些现实世界的观察结果表明，ORLADEYO可以对患有正常C1-INH的HAE患者的生活产生有意义的影响。我们期待继续评估我们的口服，每日一次的预防作为治疗选择是亚群，”博士说。

Ryan Arnold, chief medical officer of BioCryst..

生物晶体首席医疗官Ryan Arnold。。

The company also announced a new post-hoc analysis from the APeX-S clinical trial that showed a sustained reduction in HAE attacks compared to patients’ self-reported baseline attack rates.

该公司还宣布了APeX-S临床试验的一项新的事后分析，结果显示，与患者自我报告的基线发作率相比，HAE发作持续减少。

“The ability to compare patients’ treatment outcomes with their HAE attack rates at baseline is tremendously helpful to characterize the impact of a prophylactic therapy. While this analysis from APeX-S includes baseline attack rates that were retrospectively self-reported by patients, the findings are consistent with results previously reported from the pivotal APeX-2 trial, that long-term prophylaxis with ORLADEYO leads to a sustained reduction in attack rates and is an important therapeutic option for the prevention of HAE attacks,” said H.

“将患者的治疗结果与基线时的HAE发作率进行比较的能力对于表征预防性治疗的影响非常有帮助，尽管APeX-S的分析包括患者回顾性自我报告的基线发作率，但发现与先前关键的APeX-2试验报告的结果一致，即长期pORLADEYO的rophylaxis导致发作率持续下降，是预防HAE发作的重要治疗选择，“H。

James Wedner, M.D., professor of medicine in the division of allergy and immunology at the John T. Milliken department of medicine at Washington University School of Medicine..

华盛顿大学医学院John T.Milliken医学系过敏与免疫学系医学教授James Wedner博士。。

The data are being presented at the 2023 Annual Scientific Meeting of the American College of Allergy, Asthma & Immunology (ACAAI), which is being held at the Anaheim Convention Center in Anaheim, Calif., from November 9-13, 2023.

这些数据将于2023年11月9日至13日在加利福尼亚州阿纳海姆的阿纳海姆大会中心召开的美国过敏，哮喘和免疫学学院（ACAAI）2023年年度科学会议上公布。

BioCryst ACAAI 2023 Presentation Highlights

BioCryst ACAAI 2023演示文稿亮点

The presentations at ACAAI include analyses from the APeX-S clinical study and real-world data from patients taking ORLADEYO in the United States. APeX-S was a Phase 2, open label, international study evaluating the safety and effectiveness of ORLADEYO 110 mg once daily (QD) and 150 mg QD in patients with HAE Type I or Type II for up to 96 weeks in the US and 240 weeks in all other countries.

ACAAI的报告包括来自APeX-S临床研究的分析和来自美国服用ORLADEYO的患者的现实数据。APeX-S是一项开放标签的第二阶段国际研究，评估ORLADEYO 110 mg每日一次（QD）和150 mg QD在美国HAE I型或II型患者中长达96周的安全性和有效性，所有其他国家240周。

The real-world data are analyses from patient-reported results collected in the real-world clinical setting from BioCryst’s sole-source pharmacy..

真实世界的数据是从BioCryst的唯一来源药房在现实世界的临床环境中收集的患者报告结果进行的分析。。

Berotralstat Reduced Attack Rates in Patients with Hereditary Angioedema with Normal C1-Inhibitor: Real-World Outcomes; ePoster #P082; Friday, November 10, 5:30-5:45 p.m. PT; Monitor #13, Exhibit Hall

Berotralstat降低C1抑制剂正常的遗传性血管性水肿患者的发作率：现实世界的结果；ePoster＃P082；周五，11月10日，下午5:30-5:45；显示器＃13，展览厅

This analysis assessed patient-reported HAE attack rates for patients with healthcare provider-diagnosed HAE (reflective of an ICD-10 code of D84.1 or T78.3) who have normal C1-INH level and function in the United States and actively received ORLADEYO 110 mg or 150 mg QD at any timepoint between December 16, 2020 and June 15, 2023 (n=302), with data shown for up to 540 days.

该分析评估了在美国具有正常C1-INH水平和功能并积极接受ORLADEYO 110的医疗保健提供者诊断的HAE（反映ICD-10代码D84.1或T78.3）的患者的患者报告的HAE发作率mg或150 mg QD，时间点为2020年12月16日至2023年6月15日（n=302），数据显示长达540天。

Data are also reported for a subset of these patients who reported a 90-day baseline attack rate and received ORLADEYO for ≥360 days (n=103). A sizeable number of patients who received another prophylactic treatment for HAE at any time, such as lanadelumab, intravenous and subcutaneous C1-INH and androgens, were included in both cohorts. .

还报告了这些患者中报告90天基线发作率并接受ORLADEYO≥360天（n=103）的患者亚组的数据。在任何时候接受另一种HAE预防性治疗的相当数量的患者，例如lanadelumab，静脉内和皮下C1-INH和雄激素，都包括在两个队列中。。.

Patient-reported attack rates were collected by the sole-source pharmacy at baseline and at each refill (approximately every 30 days). The baseline 30-day average was calculated based on each patient’s self-reported attack rate for the 90 days prior to initiating ORLADEYO and by dividing that value by three.

患者报告的攻击率由基线和每次补充时的唯一来源药房收集（大约每30天一次）。基线30天平均值是根据每位患者在开始使用ORLADEYO前90天的自我报告发作率并将该值除以3计算的。

Monthly attack rates were calculated by taking the average of the reported attacks across each 90-day period. .

每月攻击率是根据每90天报告的攻击的平均值计算的。。.

A reduction in HAE attack rates was observed in both cohorts upon initiation of ORLADEYO:

ORLADEYO开始治疗后，两组患者的HAE发作率均有所下降：

At baseline, the median attack rate was 3.00 attacks per month (n=249). Upon initiation of ORLADEYO, median attack rates were reduced to 1.00 at Days 1-90 (n=277) and Days 91-180 (n=232); 1.29 at Days 181-270 (n=174); 1.00 at Days 271-360 (n=143); and 1.50 at Days 361-450 (n=105) and Days 451-540 (n=79), with a median attack rate of ≤1.50 attacks per month across all reporting periods over the entire duration..

在基线时，中位攻击率为每月3.00次攻击（n=249）。ORLADEYO开始后，第1-90天（n=277）和第91-180天（n=232）的中位发作率降至1.00；在第181-270天（n=174）为1.29；在第271-360天（n=143）为1.00；在361-450天（n=105）和451-540天（n=79）时为1.50，在整个报告期间，每月的中位攻击率≤1.50。。

For patients who reported a 90-day baseline attack rate and received ORLADEYO for ≥360 days (n=103), the median baseline attack rate was 3.00 attacks per month. Upon initiation of ORLADEYO, median attack rates were reduced to 1.29 at Days 1-90 (n=100); 1.00 at Days 91-180 (n=99); 1.33 at Days 181-270 (n=99); and 1.00 at Days 271-360 (n=101), with a median attack rate of ≤1.33 attacks per month across all reporting periods over the entire duration..

对于报告90天基线发作率并接受ORLADEYO≥360天（n=103）的患者，中位基线发作率为每月3.00次发作。开始使用ORLADEYO后，在第1-90天（n=100），中位发作率降至1.29；在第91-180天为1.00（n=99）；在第181-270天（n=99）为1.33；在271-360天（n=101）为1.00，在整个报告期内，每月的中位攻击率≤1.33。。

This analysis suggests that long-term prophylaxis with ORLADEYO resulted in a reduction in patient-reported monthly attack rates compared to baseline and median patient-reported attack rates remained consistently low in patients with HAE who have normal C1-INH level and function.

该分析表明，与基线相比，长期使用ORLADEYO进行预防可导致患者报告的每月发作率降低，并且具有正常C1-INH水平和功能的HAE患者的中位患者报告的发作率始终较低。

Berotralstat Reduced Attack Rates Compared to Baseline in Patients with Hereditary Angioedema in APeX-S; ePoster #P064; Saturday, November 11, 12:05-12:20 p.m. PT; Monitor #12, Exhibit Hall

与APeX-S遗传性血管性水肿患者相比，Berotralstat降低了发作率；ePoster＃P064；患者于11月11日星期六12:05-12:20；显示器＃12，展览厅

This analysis characterized the safety and effectiveness of ORLADEYO 150 mg QD in U.S. patients enrolled in the APeX-S trial who self-reported a baseline attack rate (n=147). Patients were asked to recall the average number of HAE attacks per month (attack rates) they experienced over the six months prior to beginning therapy.

该分析表征了ORLADEYO 150 mg QD在参加APeX-S试验的美国患者中的安全性和有效性，这些患者自我报告了基线发作率（n=147）。要求患者回忆他们在开始治疗前六个月中每月平均发生的HAE发作次数（发作率）。

Attack rates after beginning therapy were calculated for each patient based on the number of attacks they experienced that met predefined criteria, as specified in the study protocol, and were adjusted for the duration of treatment in each month. Attack rates at baseline were not evaluated according to the predefined criteria used for inclusion in the effectiveness analysis in APeX-S. .

根据研究方案中规定的符合预定标准的发作次数，计算每位患者开始治疗后的发作率，并根据每个月的治疗持续时间进行调整。基线攻击率没有根据用于纳入APeX-S有效性分析的预定义标准进行评估。。.

ORLADEYO was generally well tolerated, and safety was consistent with that of the entire APeX-S population.

ORLADEYO一般耐受性良好，安全性与整个APeX-S人群一致。

In patients who reported HAE attack rates at baseline, mean (SEM) attack rates declined from 2.3 (0.29) self-reported attacks per month prior to initiating ORLADEYO treatment to 0.71 (0.12) at Month 1, 0.49 (0.09) at Month 6 and 0.32 (0.10) at Month 12, respectively. A median attack rate of 0 attacks per month was observed for all months across the 12-month period. .

在基线时报告HAE发作率的患者中，平均（SEM）发作率从开始ORLADEYO治疗前每月2.3（0.29）次自我报告发作降至第1个月的0.71（0.12），第6个月的0.49（0.09）第12个月分别为0.32（0.10）。在整个12个月的时间里，所有月份的中位攻击率均为每月0次攻击。。.

Patients who were treated with ORLADEYO experienced a sustained reduction in HAE attacks compared to their self-reported baseline attack rates, suggesting a reduction in disease burden and durable treatment effect.

与自我报告的基线发作率相比，接受ORLADEYO治疗的患者HAE发作持续减少，表明疾病负担减轻和持久治疗效果。

In addition to being displayed in the exhibit hall at the noted times, ePosters are accessible online and on demand to registered attendees on ACAAI’s website.

除了在指定时间在展览厅展示外，还可以在线访问ePosters，并可根据需要在ACAAI网站上注册参加者。

About ORLADEYO® (berotralstat)

关于ORLADEYO®（berotralsate）

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.

ORLADEYO®（berotralstat）是第一个也是唯一一种专门用于预防12岁及以上成人和儿童患者遗传性血管性水肿（HAE）发作的口服疗法。每天一粒ORLADEYO胶囊可通过降低血浆激肽释放酶的活性来预防HAE发作。

U.S. Indication and Important Safety Information

U、 S.指示和重要安全信息

INDICATION

指示

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.

ORLADEYO®（berotralstat）是一种血浆激肽释放酶抑制剂，适用于预防12岁及以上成人和儿科患者的遗传性血管性水肿（HAE）发作。

Limitations of use

使用限制

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..

ORLADEYO治疗急性HAE发作的安全性和有效性尚未确定。ORLADEYO不应用于治疗急性HAE发作。由于QT间期延长的可能性，不建议每天增加剂量或剂量高于150毫克的ORLADEYO。。

IMPORTANT SAFETY INFORMATION

重要的安全信息

An increase in QT prolongation was observed at dosages higher than the recommended 150 mg once-daily dosage and was concentration dependent.

当剂量高于推荐的150mg每日一次剂量时观察到QT延长的增加并且是浓度依赖性的。

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.

接受ORLADEYO治疗的患者最常见的不良反应（≥10%且高于安慰剂）是腹痛，呕吐，腹泻，背痛和胃食管反流病。

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) and in patients taking chronically administered P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) inhibitors (eg, cyclosporine).

对于中度或重度肝功能损害患者（Child-Pugh B或C）以及长期服用P-糖蛋白（P-gp）或乳腺癌耐药蛋白的患者，建议每日口服一次110 mg口服食物BCRP）抑制剂（例如环孢菌素）。

Berotralstat is a substrate of P-gp and BCRP. 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.

Berotralstat是P-gp和BCRP的底物。P-gp诱导剂（例如利福平，圣约翰草）可以降低berotralstat血浆浓度，导致ORLADEYO的功效降低。ORLADEYO不推荐使用P-gp诱导剂。

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..

剂量为150 mg的ORLADEYO是CYP2D6和CYP3A4的中度抑制剂。对于主要由CYP2D6或CYP3A4代谢的治疗指数较窄的伴随药物，建议进行适当的监测和剂量滴定。ORLADEYO剂量为300 mg是一种P-gp抑制剂。当与ORLADEYO共同给药时，建议对P-gp底物（如地高辛）进行适当的监测和剂量滴定。。

The safety and effectiveness of ORLADEYO in pediatric patients <12 years of age have not been established.

ORLADEYO在12岁以下儿科患者中的安全性和有效性尚未确定。

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.

没有足够的数据可以告知怀孕期间使用ORLADEYO的药物相关风险。没有关于人乳中是否存在berotralstat，其对母乳喂养婴儿的影响或其对产奶量的影响的数据。

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.

要报告疑似不良反应，请致电1-833-633-2279联系BioCryst Pharmaceuticals，Inc。或致电1-800-FDA-1088或www.FDA.gov/medwatch联系FDA。

Please see full Prescribing Information.

请参阅完整的处方信息。

About BioCryst Pharmaceuticals

关于BioCryst制药

BioCryst Pharmaceuticals is a global biotechnology company with a deep commitment to improving the lives of people living with complement-mediated and other rare diseases. BioCryst leverages its expertise in structure-guided drug design to develop first-in-class or best-in-class oral small-molecule and protein therapeutics to target difficult-to-treat diseases.

BioCryst Pharmaceuticals是一家全球生物技术公司，致力于改善患有补体介导和其他罕见疾病的人的生活。BioCryst利用其在结构指导药物设计方面的专业知识开发一流或一流的口服小分子和蛋白质疗法，以针对难以治疗的疾病。

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..

BioCryst已经商业化ORLADEYO®（berotralstat），这是第一种口服，每日一次的血浆激肽释放酶抑制剂，正在推进小分子和蛋白质疗法的管道。欲了解更多信息，请访问www.biocryst.com或在LinkedIn上关注我们。。

Forward-Looking Statements

前瞻性声明

This press release contains forward-looking statements, including statements regarding future results, performance or achievements. 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.

本新闻稿包含前瞻性声明，包括有关未来成果，业绩或成就的声明。这些陈述涉及已知和未知的风险，不确定性和其他可能导致实际结果，业绩或成就与前瞻性陈述所表达或暗示的任何未来结果，业绩或成就大不相同的因素。

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: the ongoing COVID-19 pandemic, which could create challenges in all aspects of BioCryst’s business, including without limitation delays, stoppages, difficulties and increased expenses with respect to BioCryst’s and its partners’ development, regulatory processes and supply chains, negatively impact BioCryst’s ability to access the capital or credit markets to finance its operations, or have the effect of heightening many of the risks described below or in the documents BioCryst files periodically with the Securities and Exchange Commission; BioCryst’s ability to successfully implement its commercialization plans for, and to commercialize, ORLADEYO, which could take longer or be more expensive than planned; the commercial viability of ORLADEYO, including its ability to achieve 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.

这些陈述反映了我们目前对未来事件的看法，并基于假设，并受到风险和不确定性的影响。鉴于这些不确定性，您不应过分依赖这些前瞻性陈述。可能影响本文所载前瞻性陈述的一些因素包括：正在进行的新型冠状病毒肺炎大流行，这可能在生物晶体业务的各个方面带来挑战，包括但不限于生物晶体及其合作伙伴的发展，监管程序和供应链，对BioCryst进入资本或信贷市场为其运营提供资金的能力产生负面影响，或影响增加下文或文件中描述的许多风险-BioCryst定期向证券交易委员会提交文件；BioCryst成功实施ORLADEYO商业化计划并将其商业化的能力，这可能需要比计划更长或更昂贵的时间；ORLADEYO的商业可行性，包括实现市场接受的能力；FDA或其他适用的监管机构可能需要进行超出计划用于产品和候选产品的研究之外的其他研究，可能无法提供可能导致计划临床试验延迟的监管许可。

BCRXW

BCRXW

Contact:

联系方式：

John Bluth

约翰·布拉斯

+1 919 859 7910

+1 919 859 7910

jbluth@biocryst.com

jbluth@biocryst.com