Bosentan

3月11日，由意大利帕多瓦大学联合李氏大药厂控股有限公司（简称：李氏大药厂或李氏集团，股份编号：00950.HK）共同发起的跨国教育项目——2026年中欧医学继续教育项目心内科第一期“妊娠合并肺动脉高压的全程管理与治疗分享”在线成功举办。 本期会议特邀意大利地中海自由大学Sabino Iliceto教授担任病例魔方专家委员会主席，中国北京安贞医院顾虹教授担任中方主席，意大利罗马翁贝托一世综合医院Silvia Papa教授担任欧方主席。北京安贞医院何缘医生、意大利罗马翁贝托一世综合医院Francesca Ileana Adamo医生担任会议讲者，意大利罗马萨皮恩扎大学Dario Vizza教授担任会议嘉宾，北京安贞医院李强强教授担任中方嘉宾，天津医科大学总医院王宙明教授担任中方嘉宾，各方专家共同就本次会议进行了交流和探讨。 病例魔方专家委员会Sabino Iliceto主席致词 意大利地中海自由大学Sabino Iliceto教授在2026年度Matrix项目启动会上发表精彩致辞，Iliceto教授表示，Matrix项目启动以来，实现了跨越式发展，不仅项目规模持续扩大，更在中国医学界收获高度认可与广泛关注。为让更多中国医生便捷参与，本届会议特意调整时间，充分彰显项目的行业影响力与口碑。自2021年至2025年，病例魔方项目已覆盖心脏科、妇科、神经科等多个医学专科，累计开展167场专题会议，合作足迹遍布中国各地。而2026年度Matrix项目全年累计计划举办38场会议，覆盖几乎全医学学科，打造出逐年完善的医学交流“百科全书”。Iliceto教授强调，Matrix项目搭建起中国与意大利医学专家的高效交流桥梁，其核心价值是惠及中国患者、助力中国医学事业发展，感谢参与该项目的中外医学专家教授的无私分享。 会议主席致辞 首都医科大学附属北京安贞医院顾虹教授指出，妊娠期肺动脉高压与儿童遗传性肺动脉高压均为肺血管疾病中高危、疑难病种，临床诊疗风险高、管理难度大，多学科协作与个体化治疗是改善患者预后的关键，期待通过本次中意跨国交流，共享临床实战经验，为复杂病例诊疗提供更清晰思路。同时感谢 “病例魔方” 项目为中外心血管及肺血管病专科医师搭建了高效、高质量的学术交流与病例共享平台。 意大利罗马翁贝托一世综合医院Silvia Papa教授对中方团队的精心组织表示感谢，她表示肺动脉高压在特殊人群（妊娠期女性、儿童）中的诊疗一直是国际公认的临床挑战，不同国家、不同中心的经验互通极具价值，能够有效弥补单一中心临床经验的局限，期待本次病例分享与深度讨论能为全球同道提供实用的诊疗参考。 学术交流 意方病例汇报 意大利罗马翁贝托一世综合医院Francesca Ileana Adamo医生——妊娠期肺动脉高压的管理 欧方讲者 Francesca医生分享了 “妊娠期肺动脉高压的管理” 的病例：患者为30 岁女性，因6个月进行性呼吸困难、活动耐量下降就诊，无其他基础疾病，心功能分级 Ⅱ 级。6分钟步行试验距离445米，NT-proBNP为820ng/L；心电图提示右心房、右心室负荷过重，可见典型肺型P波及胸前导联T波倒置；经胸超声心动图示右心腔扩大，右心室/左心室比值大于1，右心室收缩功能减低，伴中度三尖瓣反流；右心导管检查示平均肺动脉压45mmHg，心指数2.2，肺血管阻力10 WU，急性血管扩张试验阴性，排除肺栓塞、慢性肺部疾病等诱因后，确诊为原发性肺动脉高压，依据2022年欧洲肺高压指南评估为中风险。 初始给予内皮素受体拮抗剂联合PDE5抑制剂口服联合治疗，4个月后复查，患者心功能改善至Ⅰ级，6 分钟步行距离提升530米，NT-proBNP显著下降，平均肺动脉压基本恢复正常，肺血管阻力下降50%，风险分层降至低风险。患者确诊妊娠后，考虑部分肺高压靶向药物存在致畸风险，停用内皮素受体拮抗剂，仅保留PDE5抑制剂治疗，并执行严格孕期随访，孕早期及孕中期每6–12周评估一次，孕晚期每2–4周评估一次，重点监测超声心动图、NT-proBNP及胎儿发育情况。孕中期患者病情出现恶化，心功能降至Ⅲ级，无法完成6分钟步行试验，NT-proBNP升高，评估为中高风险，及时加用曲前列尼尔肠外治疗优化方案。 分娩期按照指南建议，于孕36–38周实施硬膜外麻醉下剖宫产手术，由心脏科、产科、新生儿科组成多学科团队全程监护，产后24–72小时转入重症监护室密切监测。患者顺利分娩，无母婴并发症，产后重启内皮素受体拮抗剂，实施PDE5抑制剂+内皮素受体拮抗剂+曲前列尼尔三联靶向治疗。2023年11月复查，患者心功能恢复至Ⅰ级，6分钟步行距离恢复至孕前水平，NT-proBNP基本正常，右心导管检查提示平均肺动脉压降至28mmHg，心指数提升至3.1，肺血管阻力降至4.1 WU，长期随访病情稳定。 Francesca医生总结核心经验：妊娠期合并原发性肺动脉高压属于极高危情况，母婴死亡风险显著升高，孕前风险分层、孕期药物个体化调整、严密随访及多学科协作是改善结局的关键；产后早期为病情波动高危期，需强化监护；药物选择需严格规避致畸风险，病情恶化时及时加用肠外前列环素类药物可有效稳定病情[1]。 中方病例汇报 北京安贞医院何缘医生——儿童IPAH/HPAH患者在三联靶向药物治疗下的挑战 中方讲者何缘医生分享了 “儿童遗传性肺动脉高压（ALK1 突变）” 的病例：患者为5岁11个月女童，因6个月活动耐量下降、10天活动后气短就诊，外院检查提示右心扩大、肺动脉高压，NT-proBNP水平超过9000pg/ml，曾予低剂量波生坦、西地那治疗，症状无显著改善。转入我院后查体示静息氧饱和度98%，活动后降至94%，无明显肺部啰音及下肢水肿；心电图示窦性心动过速、电轴右偏、肺型P波，伴ST-T 改变；胸部X线示心胸比约61%，右心显著扩大；超声心动图示右心显著扩大，右心室 / 左心室比值达3.5，左心室受压，内径仅27mm，估测肺动脉收缩压103mmHg，伴轻中度三尖瓣反流，右心室收缩功能明显减低，TIPS 值仅10mm；心脏磁共振提示右心室射血分数仅23%，存在心肌纤维化；经全面基因筛查确诊为ALK1基因突变，突变来源为父亲，最终诊断为遗传性肺动脉高压，风险分层为高风险，心功能分级Ⅲ级。 入院后采用包含曲前列尼尔在内的三联靶向药物治疗方案，并将曲前列尼尔逐步加量治疗，由9ng逐步加至50ng，治疗后患者BNP及NT-proBNP水平较前明显下降，NT-proBNP由9461 pg/ml降至936 pg/ml，血氧饱和度上升，右心室收缩功能较前有所改善，SPAP由118mmHg下降至74mmHg，但未能彻底控制在低风险状态。2025 年10月尝试使用新型药物Sotatercept协助初始三联治疗方案进行干预，用药2剂后NT-proBNP降至正常，SPAP复测为82mmHg，用药5剂后SPAP降至60 mmHg，RV/LV 比值接近正常，右心功能得到改善，加用Sotatercept后患儿出现每月3-4次鼻出血、面部毛细血管扩张等不良反应，静息氧饱和度降至94%-95%。结合中心研究数据，儿童特发性及遗传性肺动脉高压以 BMPR2、ALK1 基因突变最为常见，突变携带者整体预后更差，其中 ALK1 突变者死亡率更高，此类难治性儿童肺高压患者的治疗需要保持密切关注。 综合讨论环节 针对意方病例的专家讨论 欧方主席Silvia Papa教授首先就病例核心要点展开分析，她提出妊娠期间血流动力学改变会显著加重右心室负荷，加速肺动脉高压进展，临床需重点监测右心室功能及充盈压；分娩时机与分娩方式需多学科团队共同决策，重症患者优先选择剖宫产。针对中方专家提出的妊娠适应症与终止妊娠指征问题，Silvia Papa教授解答，仅低风险肺动脉高压患者可在充分告知风险、多学科评估后谨慎妊娠，孕期若心功能恶化至Ⅲ–Ⅳ级、右心功能显著受损，应及时建议终止妊娠；孕期急性血管扩张试验常用药物为一氧化氮，需根据患者个体情况调整，避免诱发急性失代偿。 中方顾虹教授表示，意方病例的全程管理模式与中方临床实践高度契合，妊娠期患者均需停用内皮素受体拮抗剂，保留 PDE5 抑制剂，病情恶化时加用曲前列尼尔等前列环素类药物；中方中心作为妊娠期肺动脉高压转诊中心，同样采用多学科协作模式管理高危患者，对于子痫前期合并肺动脉高压患者，死亡风险仍处于较高水平，临床需更为谨慎的风险管控。双方专家一致认为，抗凝策略、药物调整、分娩监护均需高度个体化，以保障母婴安全为核心目标。中方顾虹教授对意方病例中孕期肺高压药物调整的核心原则问题也进行了提问，经过中意双方教授学者的探讨碰撞，一致认为核心原则应是规避致畸性药物，保留安全有效药物，在病情恶化时及时加用肠外药物；意方在该病例中停用内皮素受体拮抗剂、保留 PDE5 抑制剂，病情进展时加用曲前列尼尔，与中方妊娠期肺高压的药物调整实践完全一致，双方均认为该方案为临床优选。 针对中方病例的专家讨论 意方Silvia Papa教授就儿童患者皮下给药局部疼痛管理、靶向药物剂量调整等问题提问，何缘医生解答，儿童患者皮下注射局部疼痛以药物对症缓解为主，低龄儿童对治疗的耐受性优于成人，心理因素对疼痛感知影响明显；三联治疗剂量需根据病情严重程度调整，重症患儿可起始较高剂量快速稳定病情，稳定期患儿逐步上调剂量。针对穿刺部位感染并发症，中方顾虹教授分享经验，可采用中心静脉置管或 PICC 替代皮下注射，感染控制后更换注射部位，降低严重并发症风险。 意方Francesca医生提问儿童心电图异常与右心病变的鉴别要点，何缘医生表示，儿童心电图电轴右偏、肺型P波等表现缺乏特异性，需结合超声心动图、胸部X线进一步评估右心结构与功能，避免漏诊肺动脉高压。意方教授对中方肺动脉高压患者三联治疗剂量调整策略进行了提问，中方教授表示在其中心会根据病情调整剂量，重症患者可直接使用高剂量急救处理，病情稳定者逐步上调剂量，意方教授同时也分享，在意大利医学中心，患者曲前列尼尔常用剂量可达120-130ng，为中方提供了剂量参考。双方专家均认可，儿童遗传性肺动脉高压需结合基因分型制定个体化方案，新型靶向药物为难治性病例带来新希望。 会议主席总结致词 会议结束时，欧方主席Silvia Papa教授与中方主席顾虹教授共同完成总结发言。 Silvia Papa教授首先对所有参会专家的精彩分享、深入讨论以及主办方的细致组织表示诚挚感谢，她强调本次会议所分享的妊娠期肺动脉高压、儿童遗传性肺动脉高压两例病例，均为肺血管疾病领域极具代表性的疑难病例，诊疗过程复杂、临床参考价值极高。本次交流围绕特殊人群肺高压的风险评估、药物选择、多学科管理、新药应用等核心问题展开充分探讨，实现了中意双方临床经验与学术思路的深度共享，弥补了儿童肺高压领域的经验空白。她同时感谢李氏大药厂“病例魔方”项目搭建的优质国际交流平台，推动肺血管疾病诊疗理念的全球化传播，期待未来继续加强合作，开展联合研究与病例共享。 顾虹教授对本次中意国际学术交流的成果给予高度评价，她表示通过两例典型疑难病例的分享与多维度研讨，双方在妊娠期及儿童肺高压诊疗领域均获得重要启发，意方规范的孕期管理流程、药物调整策略为中方临床实践提供了重要参考。中方作为妊娠期与儿童肺高压专科转诊中心，愿意持续开放临床经验与研究数据分享，与意方深化长期合作。她希望未来能开展更多跨地域学术交流、多中心临床研究及联合科研项目，共同攻克肺血管疾病疑难领域，提升全球规范化诊疗水平，惠及更多高危患者。双方一致期待后续持续推进中意两国在肺血管病领域的学术互动与深度协作，为学科发展注入持续动力。   参考文献： [1] Marc H, Gabor K, Marius MH, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension.Eur Heart J.2022 Oct 11;43(38):3618-3731 下滑查看更多 关于李氏大药厂 - 亞太地區最具創新力的上市企業 - 李氏大药厂控股有限公司（简称：李氏大药厂或李氏集团，股份编号: 00950.HK）成立于1994年，是一家结合了研发驱动和市场导向的生物医药集团公司，总部位于香港。李氏大药厂于2002年7月在香港联合交易所（简称：“港交所”）创业板上市，并于2010年5月成功转至港交所主板上市。李氏大药厂在全球拥有三大综合性生产研发基地和两大中心，即：李氏-兆科合肥基地（位于安徽省合肥市高新区）、李氏-兆科南沙基地（位于广东省广州市南沙区）、美国加州基地和集团研发中心、集团营销中心，目前员工总数超过1100人。 李氏大药厂立足中国大陆，放眼国际，通过坚实和稳固的投入建设，全面覆盖整合了药物研发、临床研究、药政注册、生产制造、销售与市场推广等各个环节。集团集中于心血管科、妇科与产科、儿科、罕见病、肿瘤科、皮肤科、精神科等多个重要疾病领域开发不同阶段的专利新药和高端仿制药。李氏大药厂与20余家国际公司建立了广泛的合作关系，目前在中国大陆、香港、澳门及台湾地区推广及销售25种包含专利新药、仿制药物及授权引进的国外已上市进口药品。 李氏大药厂现有超过40个处于不同开发阶段的产品，既有自主研发产品，也有通过来自美国、欧洲及日本等公司通过授权引进进行研发、生产以及商业化的产品。 李氏大药厂的使命是致力于研发新药，治疗顽疾，改善生活质量，为患者带来福音，目标成为亚洲成功的生物制药集团，提供治疗疾病和改善生活质量的创新产品。 下滑查看更多 免责声明：本会议报道仅限医学专业人士学术交流，不涉及任何药品推广，不作为诊疗依据。因本报道全部或任何部分内容而产生或因倚赖该等内容而引致的任何损失不承担任何责任。 撰稿：李阳 排版：黄文浩  校稿：樊扬波 审核：张超 与“李”同行 招商热线 020-39062882 公众号 小程序 视频号 小红书

SILVER SPRING, Md. & RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)--United Therapeutics Corporation (Nasdaq: UTHR), a public benefit corporation, today announced that its TETON-1 study evaluating the use of nebulized Tyvaso for the treatment of idiopathic pulmonary fibrosis (IPF) met its primary efficacy endpoint, demonstrating superiority over placebo for the change in absolute forced vital capacity (FVC) by 130.1 mL (Hodges-Lehmann [H-L] estimate, 95% confidence interval [CI], 82.2 to 178.1 mL; p <0.0001) from baseline to week 52. Nebulized Tyvaso achieved statistical significance for reducing the risk of clinical worsening and showed numerical improvement in other important secondary endpoints relative to placebo, including time to first acute exacerbation of IPF and changes in percent predicted FVC, King’s Brief Interstitial Lung Disease quality of life questionnaire (K-BILD) score, and diffusion capacity of lungs for carbon monoxide (DLCO). Benefits of nebulized Tyvaso were observed across all subgroups, such as use of background therapy (nintedanib, pirfenidone, or no background therapy), smoking status, and supplemental oxygen use. Treatment with nebulized Tyvaso was well-tolerated, and the safety profile was consistent with previous Tyvaso studies and known prostacyclin-related adverse events. No new safety signals were observed. Integrated analyses of TETON-1 and TETON-2 showed statistically significant treatment effects compared to placebo from baseline to week 52 for the primary endpoint of change in absolute FVC by 111.8 mL (H-L estimate, 95% CI, 79.7 to 144.0; p <0.0001) and most secondary endpoints, including time to first clinical worsening and first acute exacerbation of IPF and changes in percent predicted FVC, K-BILD score, and DLCO. Overall survival at week 52 trended in favor of Tyvaso but did not meet statistical significance. “The unprecedented results of TETON-1, which surpassed even the overwhelmingly positive results of TETON-2, represent a profound step forward for people living with IPF, a devastating disease with few treatment options. We remain sincerely grateful to the patients, caregivers, and investigators who made this trial possible,” said Martine Rothblatt, Ph.D., Chairperson and Chief Executive Officer of United Therapeutics. “In the past seven months, our three pivotal studies, TETON-1, TETON-2, and the ADVANCE OUTCOMES study of ralinepag, met their primary endpoints with p-values <0.0001, an inflection point heralding a new era of even greater growth for United Therapeutics. These consecutive accomplishments were produced by our culture of innovation and our commitment to multiple shots on goal to advance treatments for rare cardiopulmonary and respiratory diseases.” “IPF is a progressive, life-limiting disease for which existing treatments provide only modest benefit and are often accompanied by significant side effects. TETON-1 reinforces what was shown in TETON-2, with both studies demonstrating clinically meaningful treatment outcomes in IPF patients with or without background anti-fibrotic therapy. Together, both studies demonstrated not only better preservation of lung function, but also preservation of quality of life, as well as reduced disease worsening and reduced acute IPF exacerbations. These findings have the potential to fundamentally shift our approach to IPF management and could be a game changer,” said Steven D. Nathan, M.D., Schar Chair, Advanced Lung Disease and Lung Transplant Program at Inova Fairfax Hospital and Chair of the TETON Steering Committee. “The TETON program has achieved statistical significance in endpoints that have never been attained in other IPF clinical trials. These results provide a compelling body of evidence for nebulized Tyvaso’s differentiated direct lung delivery combined with multimodal activity across fibrotic, vascular, and inflammatory pathways that are not currently addressed by existing therapies,” said Peter Smith, Pharm.D., Senior Vice President, Product Development at United Therapeutics and the lead for the global TETON program. United Therapeutics plans to seek priority review of a supplemental New Drug Application, to be submitted to the U.S. Food and Drug Administration (FDA) by the end of this summer, to add IPF to the labeled indications for nebulized Tyvaso based on data from the TETON-1 and TETON-2 studies. Both the FDA and the European Medicines Agency have granted orphan designation for treprostinil to treat IPF. Additional TETON-1 study results and data from the integrated analyses of TETON-1 and TETON-2 will be presented at the American Thoracic Society Annual Meeting in Orlando in May 2026. Full results of the TETON-2 study were recently published in the New England Journal of Medicine and are available online at NEJM.org. TETON Clinical Program A post-hoc analysis of the INCREASE study in patients with pulmonary hypertension associated with interstitial lung disease suggested that nebulized Tyvaso was associated with a significant improvement in FVC, laying the foundation for the TETON clinical program to evaluate the use of nebulized Tyvaso in IPF and progressive pulmonary fibrosis (PPF). TETON-1 enrolled patients with IPF in the United States and Canada, and TETON-2 enrolled patients with IPF outside the United States and Canada. TETON-PPF is evaluating the use of nebulized Tyvaso in PPF in patients globally, and enrollment is ongoing. TETON-1 Study Design The TETON-1 study (NCT04708782) was a 598-patient, multicenter, randomized, double-blind, placebo-controlled phase 3 registration study evaluating the safety and efficacy of nebulized Tyvaso in patients with IPF over a 52-week period at sites in the United States and Canada. The study reached full enrollment in January 2025. The primary endpoint of the study was the change in absolute FVC from baseline to week 52. Secondary endpoints included: (1) time to clinical worsening; (2) time to first acute exacerbation of IPF; (3) overall survival at week 52; (4) change in percent predicted FVC from baseline to week 52; (5) change in the K-BILD questionnaire from baseline to week 52; and (6) change in DLCO from baseline to week 52. Safety assessments included the development of adverse events, serious adverse events, vital signs, clinical laboratory parameters, and electrocardiogram parameters. Eligible patients completing the TETON-1 study could enroll in the TETON-OLE study (NCT04905693), an ongoing open-label extension study to evaluate the long-term safety and tolerability of nebulized Tyvaso in patients with fibrotic lung disease. About IPF Idiopathic pulmonary fibrosis, or IPF, is a scarring disease of the lungs of an unknown (idiopathic) cause and is the most common of the idiopathic interstitial pneumonias. IPF is characterized by the progressive loss of the ability of the lungs to transfer oxygen into the blood, ultimately resulting in respiratory failure and death. While the precise causes of IPF remain unknown, IPF rarely presents before age 50 and can be associated with cigarette smoking and certain genetic dispositions. In addition, some evidence suggests that gastroesophageal reflux (acid reflux, or heartburn), certain viral infections, air pollution, and workplace exposures may be risk factors for IPF. IPF is estimated to affect between 0.33 and 4.51 people per 10,000 persons worldwide. Further, United Therapeutics estimates there are over 100,000 IPF patients in the United States. About Tyvaso® (treprostinil) Inhalation Solution INDICATION TYVASO (treprostinil) Inhalation Solution is a prostacyclin mimetic indicated for the treatment of: Pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability. Studies with TYVASO establishing effectiveness predominately included patients with NYHA Functional Class III symptoms and etiologies of idiopathic or heritable PAH (56%) or PAH associated with connective tissue diseases (33%). The effects diminish over the minimum recommended dosing interval of 4 hours; treatment timing can be adjusted for planned activities. While there are long-term data on use of treprostinil by other routes of administration, nearly all clinical experience with inhaled treprostinil has been on a background of an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor. The controlled clinical experience with TYVASO was limited to 12 weeks in duration. Pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability. The study with TYVASO establishing effectiveness predominately included patients with etiologies of idiopathic interstitial pneumonia (IIP) (45%) inclusive of idiopathic pulmonary fibrosis (IPF), combined pulmonary fibrosis and emphysema (CPFE) (25%), and WHO Group 3 connective tissue disease (22%). IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS TYVASO is a pulmonary and systemic vasodilator. In patients with low systemic arterial pressure, TYVASO may produce symptomatic hypotension. TYVASO inhibits platelet aggregation and increases the risk of bleeding. Co-administration of a cytochrome P450 (CYP) 2C8 enzyme inhibitor (e.g., gemfibrozil) may increase exposure (both Cmax and AUC) to treprostinil. Co-administration of a CYP2C8 enzyme inducer (e.g., rifampin) may decrease exposure to treprostinil. Increased exposure is likely to increase adverse events associated with treprostinil administration, whereas decreased exposure is likely to reduce clinical effectiveness. Like other inhaled prostaglandins, TYVASO may cause acute bronchospasm. Patients with asthma or chronic obstructive pulmonary disease (COPD), or other bronchial hyperreactivity, are at increased risk for bronchospasm. Ensure that such patients are treated optimally for reactive airway disease prior to and during treatment with TYVASO. DRUG INTERACTIONS/SPECIFIC POPULATIONS The concomitant use of TYVASO with diuretics, antihypertensives, or other vasodilators may increase the risk of symptomatic hypotension. Human pharmacokinetic studies with an oral formulation of treprostinil (treprostinil diolamine) indicated that co-administration of the cytochrome P450 (CYP) 2C8 enzyme inhibitor, gemfibrozil, increases exposure (both Cmax and AUC) to treprostinil. Co-administration of the CYP2C8 enzyme inducer, rifampin, decreases exposure to treprostinil. It is unclear if the safety and efficacy of treprostinil by the inhalation route are altered by inhibitors or inducers of CYP2C8. Limited case reports of treprostinil use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. However, pulmonary arterial hypertension is associated with an increased risk of maternal and fetal mortality. There are no data on the presence of treprostinil in human milk, the effects on the breastfed infant, or the effects on milk production. Safety and effectiveness in pediatric patients have not been established. Across clinical studies used to establish the effectiveness of TYVASO in patients with PAH and PH ILD, 268 (47.8%) patients aged 65 years and over were enrolled. The treatment effects and safety profile observed in geriatric patients were similar to younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of hepatic, renal, or cardiac dysfunction, and of concomitant diseases or other drug therapy. ADVERSE REACTIONS Pulmonary Arterial Hypertension (WHO Group 1) In a 12-week, placebo-controlled study (TRIUMPH I) of 235 patients with PAH (WHO Group 1 and nearly all NYHA Functional Class III), the most common adverse reactions seen with TYVASO in ≥4% of PAH patients and more than 3% greater than placebo were cough (54% vs 29%), headache (41% vs 23%), throat irritation/pharyngolaryngeal pain (25% vs 14%), nausea (19% vs 11%), flushing (15% vs <1%), and syncope (6% vs <1%). In addition, adverse reactions occurring in ≥4% of patients were dizziness and diarrhea. Pulmonary Hypertension Associated with ILD (WHO Group 3) In a 16-week, placebo-controlled study (INCREASE) of 326 patients with PH-ILD (WHO Group 3), adverse reactions with TYVASO were similar to the experience in studies of PAH. Please see Full Prescribing Information for TYVASO, the TD-300 TYVASO® Inhalation System Instructions for Use manual, and additional information at www.TYVASOHCP.com or call 1 844 UNITHER (1-844-864-8437). About United Therapeutics Founded by CEO Martine Rothblatt to discover a cure for her daughter's life-threatening rare disease, pulmonary arterial hypertension, United Therapeutics transforms the treatment of rare diseases and pioneers alternatives to expand the supply of transplantable organs. From our innovative therapies to our groundbreaking manufactured organs, we are bold and unconventional. We move quickly from scientific theory to practical technologies that can save lives. As a public benefit corporation, even our legal structure reflects our commitments. We serve patients, act with integrity, create long-term shareholder value, and operate with sustainable practices that protect the future we are working to build. Visit us at www.unither.com and follow us on LinkedIn, Facebook, and Instagram. Forward-Looking Statements Statements included in this press release that are not historical in nature are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include, among others, statements regarding the timing and outcome of our planned regulatory submission to the FDA to seek approval to add IPF to the labeled indications for nebulized Tyvaso, including our plan to seek priority review; our expectations concerning the potential benefits of nebulized Tyvaso for IPF patients, including the possibility that the results of the TETON-1 and TETON-2 studies could fundamentally shift the approach to IPF management; our belief that the results of the TETON-1, TETON-2, and ADVANCE OUTCOMES studies will lead to a new era of growth for United Therapeutics; statements regarding our ongoing TETON-PPF study of nebulized Tyvaso in patients with PPF; and our goals of expanding the supply of transplantable organs, developing practical technologies that can save lives, creating long-term shareholder value, and operating with sustainable practices. These forward-looking statements are subject to certain risks and uncertainties, such as those described in our periodic reports filed with the Securities and Exchange Commission, that could cause actual results to differ materially from anticipated results. Consequently, such forward-looking statements are qualified by the cautionary statements, cautionary language, and risk factors set forth in our periodic reports and documents filed with the Securities and Exchange Commission, including our most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K. We claim the protection of the safe harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. We are providing this information as of March 30, 2026, and assume no obligation to update or revise the information contained in this press release whether as a result of new information, future events or any other reason. TYVASO is a registered trademark of United Therapeutics Corporation.