Bosentan

– A single intravitreal administration of PER-001 improved both visual function and anatomic structure compared to control at 24 weeks – – These data support the potential of PER-001 as the first disease-modifying treatment for glaucoma – –PER-001 improved ocular blood flow, validating target engagement and the sustained release profile of PER-001, enabling a convenient six-month dosing frequency – – PER-001 was safe and well-tolerated over 24 weeks – – Company plans to initiate a pivotal-enabling Phase 2b trial in the second half of 2025 – SAN FRANCISCO, May 6, 2025 /PRNewswire/ -- Perfuse Therapeutics, Inc. ("Perfuse Therapeutics"), a biopharmaceutical company pioneering transformational therapies to treat ischemia-induced ocular diseases, today announced positive 24-week results from its completed Phase 1/2a trial of PER-001, a first in class endothelin antagonist intravitreal implant for glaucoma. Steven Mansberger, MD, MPH, Chief of Ophthalmology and Director of Glaucoma Services at Legacy Devers Eye Institute, and an Investigator in the study, shared the results today in an oral presentation at the Association for Research in Vision and Ophthalmology (ARVO) Meeting. Data from the trial showed a single intravitreal administration of PER-001, added to existing standard-of-care intraocular pressure (IOP) reducing therapies, increased ocular blood flow and improved both visual function and anatomic structure, each of which are registrable outcomes, as measured by visual field (VF) sensitivity and optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness. PER-001 was safe and well-tolerated over the six-month study period. "Our mission is to develop the first disease-modifying treatment for glaucoma, the leading cause of irreversible global blindness with no approved therapies," said Sevgi Gurkan, MD, CEO and Founder of Perfuse Therapeutics. "These data are very promising, with PER-001 improving vision in glaucoma patients. We plan to advance the clinical development of PER-001, with initiation of an adaptive Phase 2b trial in glaucoma in the second half of 2025 that we believe could serve as one of two pivotal studies required for registration." "For decades, glaucoma treatments have focused on lowering intraocular pressure (IOP). Yet, many patients still experience vision loss and progress to blindness," said Dr. Mansberger. "What is particularly remarkable is that treatment with PER-001 led to improvements in ocular blood flow, optic nerve structure, and visual function. These findings suggest a potentially transformative approach for the treatment of glaucoma by targeting the endothelin pathway, a well-established mediator of vascular dysfunction in the disease. Notably, this represents the first time endothelin antagonism has been studied in the human eye, marking the potential start of an exciting new era of treatment for patients with glaucoma." PER-001 Phase 1/2a Study Design The Phase 1/2a clinical trial was a multi-center two-part trial designed to assess the safety and tolerability of the PER-001 intravitreal implant in patients with glaucoma. Exploratory objectives included pharmacodynamic (optic nerve head blood flow), functional (VF), and structural (OCT RNFL) effects of PER-001. The Phase 1 part of the trial, a first-in-human, open-label, single ascending dose (SAD) study, assessed the safety and tolerability of two doses of a single PER-001 administration in six patients with advanced glaucoma (n=3 per dose). Phase 2a, a randomized, patient and reading center masked study, evaluated the PER-001 low and high dose against sham control in patients with progressive mild-to-moderate glaucoma (n=approximately 8 for each of the low dose, high dose, and sham control groups). A total of 33 participants were enrolled and received a single intravitreal PER-001 administration or sham injection while continuing their existing pre-study IOP-lowering treatments. Participants were followed for 24 weeks after dosing. PER-001 Safety Results For the Phase 1/2a study, the 24-week data demonstrated that PER-001 was safe and well-tolerated. There were two drug-related adverse events of vitreous floaters, both of which were mild, intermittent, and self-resolved. No other drug-related adverse events or serious adverse events were reported. Additionally, there were no reports of endophthalmitis, intraocular inflammation, uveitis, or retinal vasculitis. There were no changes in IOP therapy, and best-corrected visual acuity was stable during the trial. PER-001 Exploratory Efficacy Results Increased ocular blood flow (Mean Blur Rate). For patients treated with PER-001, a clinically meaningful increase in optic nerve head blood flow from baseline was observed starting at Week 1 and was sustained out to Week 24 for both doses combined across Phase 1/2a. Improved function (VF). Patients treated with PER-001 showed improved vision; the improvement in VF mean deviation from baseline was +1.5 and +1.1 decibel (dB) per year at 24 weeks for high dose and low dose, respectively, in Phase 2a. In contrast, the sham control group worsened in VF mean deviation of –1.2 dB per year over the same period. Improved structure (OCT RNFL). Patients treated with PER-001 showed improved anatomic structure; the increase in RNFL thickness from baseline was +7.7 and +2.4 microns per year for low dose and high dose, respectively, as measured by OCT at 24 weeks in Phase 2a. In contrast, the sham control group had a decrease in RNFL thickness of –6.8 microns per year over the same period. There was a strong, linear relationship between the functional (VF) and structural (RNFL) improvements (Pearson Correlation Coefficient = 0.721; p = 0.0003; R² = 0.52). The presentation, "PER-001, an endothelin antagonist, increased optic nerve head blood flow with structural and functional improvements in patients with glaucoma", is available under the News section of the Company's website. The abstract can be found on the ARVO website. About PER-001 Intravitreal Implant, a Long-Acting Endothelin Receptor Antagonist PER-001 is a novel (new chemical entity), first-in-class small molecule endothelin receptor antagonist. Endothelin is the most potent vasoconstrictor in the human body and is upregulated in glaucoma. Endothelin is involved in inflammation and cell death through its receptors expressed in retinal vascular and neuroretinal cells. The PER-001 intravitreal implant is a bio-erodible implant administered into the vitreous cavity of the eye using a single-use, 25-gauge applicator and designed to provide a sustained release of PER-001, allowing for a convenient every 6 months dosing frequency. About Open-Angle Glaucoma In the United States, approximately four million people are diagnosed with glaucoma, and its prevalence is projected to double within the next 15 years. The current standard of care is solely directed towards lowering intra-ocular pressure (IOP), the only known modifiable risk factor. Despite the availability of pharmacological, laser, and surgical treatments to lower IOP, there are no FDA-approved therapies for glaucoma. Unfortunately, even with effective IOP-lowering treatments, many patients continue to experience vision loss. Globally, glaucoma remains the leading cause of irreversible blindness. About Perfuse Therapeutics Perfuse Therapeutics is a biopharmaceutical company pioneering transformational therapies to treat ischemia-induced ocular diseases. Enabled by its proprietary sustained-release drug delivery platform, the Company is developing a robust pipeline of novel assets against validated targets. Headquartered in South San Francisco, California, and with R&D facilities in Durham, North Carolina, Perfuse Therapeutics has established a strong team committed to advancing disease-modifying therapies to patients with ocular disease around the world. For more information, please see and on LinkedIn. Contact: Lori Rosen Red House Communications [email protected] SOURCE Perfuse Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

点击蓝字关注我们肺动脉高压（PAH）是一种罕见、进展快速且最终危及生命的进展性心血管疾病，其特征是肺血管重构，导致肺动脉管腔进行性闭塞，肺血管阻力不断升高，进而导致心力衰竭甚至死亡。       关于肺动脉高压       根据柳叶刀杂志报道，全球患肺动脉高压的人数占世界人口总量的1％，常见于30至60岁的女性，约五分之一的患者有家族病史。PAH 的诊断常被延误，因为其症状如：呼吸短促、疲劳、脚和腿肿胀、头晕或昏厥、胸痛、心悸等与常见的心脏和肺部疾病的症状相似。从病理学机制上看，肺动脉高压是多个信号通路及环境因素、基因因素共同作用的结果。绿色箭头=通路激活剂，红色箭头=通路抑制剂，蓝色方框=通路，红色方框=通路抑制剂、绿色方框=通路激活物/调节剂。  肺动脉高压现有治疗药物  在缺乏靶向药物的传统治疗时代， PAH患者预后差，存活时间短，5年生存率仅有20%左右。自靶向药物广泛用于临床后，PAH患者生存率显著提高，5年生存率达到近60%。现阶段肺动脉高压的治疗方式仍以靶向药为主，目前PAH的靶向药物治疗主要针对三大致病途径调节血管收缩或舒张，包括内皮素通路、一氧化氮通路、前列环素通路。内皮素通路:内皮素受体拮抗剂(ERA)一氧化氮通路:磷酸二酯酶抑制剂(PDE5i)、可溶性鸟苷酸环化酶(sGC) 激动剂前列环素通路:前列环素及其类似物、前列环素IP受体激动剂目前国内已上市的PAH靶向药有波生坦、安立生坦、马昔腾坦；西地那非、他达拉非、利奥西呱；吸入伊洛前列素、皮下和静脉注射曲前列尼尔、司来帕格等。  临床治疗亟需更有效药物  既然现有的靶向药已经能够改善病症，为什么患者死亡率并没有显著改善？为什么新靶点药物仍受到研究人员高度关注？肺动脉高压的特征是肺血管重构，肺动脉管腔狭窄闭塞。血流通过肺血管时的阻力增大，导致缺氧和右心功能衰竭。现有的PAH靶向药如波生坦、西地那非、利奥西呱等，通过各种途径促进肺血管扩张，让血流通过顺畅一些，缓解患者症状，使患者能维持较好的生活质量，但未从源头上抑制疾病进展，即所谓“治标不治本”。肺动脉高压的治疗亟需打破过去单纯肺血管扩张模式，聚焦逆转肺血管重构的高效的全新一代治疗药物。2024年3月26日，美国食品药品管理局（FDA）批准由Acceleron Pharma和MERCK联合开发的sotatercept（商品名：Winrevair）用于治疗成年人的肺动脉高压，以增加运动能力，改善WHO功能分级并降低临床恶化事件的风险。该药物每瓶定价14000美元，全年的费用约为24.2万美元，约175万人民币。摩根大通股票分析师 Chris Schott预测到2030年，销售额可接近50亿美元。与传统药物不同，Sotatercept是一种激活素信号抑制剂，是First-in-class激活素受体IIA-Fc型（ActRIIA Fc）融合蛋白，可选择性结合TGF-β家族配体，恢复肺动脉壁和右心室重构相关的促增殖和抗增殖信号通路之间的平衡，机制上具有抑制平滑肌细胞增殖、逆转肺动脉壁和右心室重构潜力，但仍需更多直接的临床证据证实。广州喜鹊医药有限公司独家开发的创新1类化学药物MN-08，既能拮抗NMDA受体、改善患者症状，又能在体内释放一氧化氮，扩张血管增加血流。在临床前药效学实验中显示出良好的药效，在肺和脑组织中具有很高的药物浓度分布，可以扩张肺动脉和脑血管。在肺动脉高压的病理状态下，NMDA受体过度激活导致谷氨酸超载、肺血管收缩、增生和纤维化。MN-08可借助特殊的分子结构参与到这一过程中，从而抑制谷氨酸超载。同时，MN-08分子中的一氧化氮供体基团可释放一氧化氮，有助于舒张肺血管、降低肺动脉压，改善肺血流循环、抑制肺血管重构和纤维化。MN-08治疗肺动脉高压中国临床 1 期及 2 期第一阶段单次给药开放试验结果已显示明确的肺动脉压力下降及增加心输出量的效果，目前正在开展中国临床2期第二阶段研究。本文部分内容来源于：梅斯心血管新前沿。内容仅供参考，不构成任何投资及应用建议，亦不代表任何治疗指导及用药建议。如稿件涉及版权等问题，请与我司联系，我们将在第一时间协调给予处理或删除。