Brimonidine Tartrate

▎药明康德内容团队编辑百时美施贵宝重磅免疫疗法组合再获FDA批准百时美施贵宝（Bristol Myers Squibb）日前宣布，美国FDA批准Opdivo（nivolumab）联合Yervoy（ipilimumab）扩展适应症，一线治疗不可切除或转移性微卫星不稳定高（MSI-H）或错配修复缺陷（dMMR）结直肠癌（CRC）患者。该批准基于CheckMate-8HW试验，该试验评估了在各治疗线中Opdivo联合Yervoy（n=354）对比Opdivo单药治疗（n=353）以及在一线治疗中Opdivo联合Yervoy（n=202）对比研究者选择化疗（n=101）的效果。在全部治疗线中以及在一线治疗中，经盲法独立中心评审（BICR）评估，Opdivo联合Yervoy均达到了无进展生存期（PFS）的主要终点。Opdivo联合Yervoy在一线治疗中与化疗相比，降低了疾病进展或死亡风险79%，在所有治疗线中与Opdivo单药相比，降低了疾病进展或死亡风险38%。Opdivo是一种PD-1免疫检查点抑制剂，旨在帮助恢复抗肿瘤免疫反应，利用人体自身的免疫系统来对抗癌症。Yervoy则靶向抑制CTLA-4。CTLA-4抗体通过增强T细胞活性来提高肿瘤杀伤能力。该产品已于2011年获得美国FDA批准治疗晚期黑色素瘤，是全球首个获批上市的CTLA-4抗体药物。潜在重磅抗体偶联药物获欧盟委员会批准阿斯利康（AstraZeneca）和第一三共（Daiichi Sankyo）联合宣布，Datroway（datopotamab deruxtecan）已获欧盟委员会批准，用于治疗接受过内分泌治疗且在晚期至少接受过一线化疗的不可切除或转移性激素受体（HR）阳性、HER2阴性乳腺癌成年患者。欧盟委员会的批准是基于3期临床试验TROPION-Breast01的结果。经BICR评估，Datroway与研究者选择的化疗相比，使HR阳性、HER2阴性转移性乳腺癌患者的疾病进展或死亡风险降低了37%（HR=0.63；95% CI：0.52-0.76；p<0.0001）。Datroway组的中位PFS为6.9个月，而化疗组为4.9个月。Datroway组的确认客观缓解率（ORR）为36%，而化疗组为23%。Datroway组的中位缓解持续时间（DoR）为6.7个月（95% CI：5.6-9.8），化疗组为5.7个月（95% CI：4.9-6.8）。Datroway是一款由人源化、靶向Trop2的单克隆抗体与创新DNA拓扑异构酶I抑制剂（DXd），通过可裂解的四肽连接子偶联生成的抗体偶联药物（ADC）。DXd具有独特的作用机制，与常见化疗药物伊立替康相比，活性提高10倍。而且此药物具有很强渗透细胞膜的能力，让它们在杀伤摄入ADC的癌细胞之后，能够杀死附近的癌细胞，产生“旁观者效应”（bystander effect）。Trop2是在多种实体瘤中广泛表达的蛋白，其中包括HR阳性、HER2低表达或阴性乳腺癌。阿斯利康和第一三共在2020年7月达成协议，合作开发这款ADC。疗效长达8小时！老花眼眼药水递交上市申请Tenpoint Therapeutics日前宣布，该公司已向美国FDA提交了Brimochol PF滴眼液的新药申请（NDA），用于治疗老花眼。该NDA的提交得到了关键性3期临床试验BRIO-I和BRIO-II研究中积极数据的支持。近日公布的BRIO-II数据显示，相较于对照组，Brimochol PF在所有时间点（最长至8小时）显著改善患者的近视力（p<0.008）。Brimochol PF还在所有时间点显示出具有临床意义和统计学显著的瞳孔缩小效果。瞳孔缩小是缩瞳药物类别疗法的关键作用机制，通过形成针孔效应，矫正近视力丧失并增加景深。Brimochol PF结合了卡巴胆碱和溴莫尼定两种获批药物。缩瞳剂卡巴胆碱在缩小瞳孔的同时，可能刺激控制晶状体形状的睫状体肌肉的收缩，改变晶状体的形状，导致它的屈光特征发生变化和引起远视力下降。经常接受治疗的患者还会出现头痛、近视移位、眼睛发红等副作用。溴莫尼定是一种α2受体激动剂，它可以起到抑制睫状体肌肉收缩和减少红眼的作用，还可以提高卡巴胆碱的半衰期，让它的效果可以持续8-12个小时，这意味着早上滴一次眼药水效果可能持续一整天。参考资料：[1] U.S. Food and Drug Administration Approves Opdivo® (nivolumab) plus Yervoy® (ipilimumab) as a Treatment for Patients with Previously Untreated Microsatellite Instability-High or Mismatch Repair Deficient Unresectable or Metastatic Colorectal Cancer. Retrieved April 11, 2025, from https://news.bms.com/news/details/2025/U-S--Food-and-Drug-Administration-Approves-Opdivo-nivolumab-plus-Yervoy-ipilimumab-as-a-Treatment-for-Patients-with-Previously-Untreated-Microsatellite-Instability-High-or-Mismatch-Repair-Deficient-Unresectable-or-Metastatic-Colorectal-Cancer1/default.aspx[2] DATROWAY® Approved in the EU for Patients with Previously Treated Metastatic HR Positive, HER2 Negative Breast Cancer. Retrieved April 11, 2025, from https://www.businesswire.com/news/home/20250407125323/en/DATROWAY-Approved-in-the-EU-for-Patients-with-Previously-Treated-Metastatic-HR-Positive-HER2-Negative-Breast-Cancer[3] Tenpoint Therapeutics Ltd. Submits New Drug Application to U.S. FDA for BRIMOCHOL™ PF for the Treatment of Presbyopia. Retrieved April 11, 2025, from https://www.businesswire.com/news/home/20250408026931/en/Tenpoint-Therapeutics-Ltd.-Submits-New-Drug-Application-to-U.S.-FDA-for-BRIMOCHOL-PF-for-the-Treatment-of-Presbyopia免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。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。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

LONDON & SEATTLE--(BUSINESS WIRE)--Tenpoint Therapeutics, Ltd. (“Tenpoint”), a global, clinical-stage biotechnology company focused on developing groundbreaking treatments to rejuvenate vision in the aging eye, today announced that the Company has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for BRIMOCHOL™ PF for the treatment of presbyopia, an age-related near-vision loss condition impacting approximately two billion people globally and 128 million people in the United States.1 “As we accelerate the build-out of our commercial team in preparation for the anticipated launch in the first half of 2026, we are incredibly proud of the dedication and tireless work that has brought the company to this point.” “The submission of the U.S. NDA for BRIMOCHOL PF marks a significant milestone for our company,” said Henric Bjarke, Chief Executive Officer at Tenpoint Therapeutics. “As we accelerate the build-out of our commercial team in preparation for the anticipated launch in the first half of 2026, we are incredibly proud of the dedication and tireless work that has brought the company to this point. We look forward to collaborating closely with the FDA throughout the NDA review process.” BRIMOCHOL PF offers the potential for a best-in-class product profile, achievable through the unique combination of brimonidine and carbachol in a pupil-modulating eye drop. This combination produces a “pinhole effect,” intended to improve the depth of focus and sharpening near and distant images, with the benefit of greater peak efficacy and duration relative to monotherapy alone. This formulation would be the first combination therapy for presbyopia if approved by the FDA. The NDA submission is supported by positive data from the first pivotal Phase 3 BRIO-I study, which demonstrated the benefit of the combination therapy over the individual components – a requirement for FDA approval of a fixed-dose combination. In a second vehicle-controlled Phase 3 BRIO-II study, BRIMOCHOL PF achieved all primary and secondary near vision improvement endpoints with statistically significant three-lines or greater improvement in binocular uncorrected near visual acuity (BUNVA) over 8 hours, without the loss of one line or more in binocular uncorrected distance visual acuity (BUDVA). In addition, BRIMOCHOL PF was well-tolerated with no serious treatment-related adverse events observed in the over 70,000 treatment days monitored in the BRIO-II study. “The NDA submission includes data from the world’s largest and longest (12 months) efficacy and safety study in presbyopia, with more than 70,000 dosing days of data. BRIMOCHOL PF demonstrated a very favorable tolerability profile and no reduction in efficacy over the 12-month study duration,” said Rhett Schiffman M.D., M.S., M.H.S.A., Chief Medical Officer and Head of Research and Development. “We also observed additional patient benefits beyond near vision improvements such as statistically significant increases in reading speed and significant lower rates of hyperemia (eye redness) compared with carbachol (p=0.001) and importantly, the rate of vitreous detachment was similar to vehicle. The increase in peak effect and duration of BRIMOCHOL PF over carbachol alone2, along with the decreased incidence of hyperemia3 and the lower rate of vitreous detachment4 are all consistent with previously reported mechanisms of action of brimonidine or related compounds.” The FDA will conduct a standard 60-day filing review to assess the completeness and acceptability of the application for formal review. About BRIMOCHOL™ PF and BRIO-II Phase 3 Study BRIMOCHOL PF is an investigational, preservative-free, once daily eyedrop to correct for the loss of near vision associated with aging. BRIO-II is a 3-arm, multicenter, randomized, double-masked, safety and efficacy study of BRIMOCHOL PF (carbachol/brimonidine tartrate fixed-dose combination) topical ophthalmic solution vs. carbachol monotherapy topical ophthalmic solution vs. a vehicle topical ophthalmic solution in subjects with emmetropic phakic or pseudophakic presbyopia (NCT05135286). The study enrolled 629 subjects across forty-seven sites in the United States. About Tenpoint Therapeutics Tenpoint Therapeutics Limited is a global, clinical-stage biotech company developing groundbreaking treatments to rejuvenate vision in the aging eye. Its pipeline includes paradigm-shifting treatments for ophthalmic indications with the greatest need and global market potential, including presbyopia, cataracts, and geographic atrophy. Its lead asset, BRIMOCHOL PF, is a novel pupil-modulating therapeutic designed to correct the loss of near vision associated with presbyopia, a condition that afflicts approximately two billion people globally. BRIMOCHOL PF has completed two large Phase 3 pivotal trials (BRIO-I and BRIO-II) and has submitted its NDA to the US FDA. Tenpoint’s leadership team includes ophthalmic industry luminaries with track records of successful approvals and commercialization of blockbuster drugs. A privately held company, Tenpoint Therapeutics is backed by AdBio Partners, AlbionVC, British Business Bank (formerly British Patient Capital), Eight Roads, EQT Life Sciences, F-Prime Capital, Hillhouse Capital Management, Qiming Venture Partners USA, Sofinnova Partners, and Wille AG. To learn more, visit tenpointtherapeutics.com and connect on LinkedIn. References Zebardast N, Friedman DS, Vitale S. The prevalence and demographic associations of presenting near-vision impairment among adults living in the United States. Am J Ophthalmol . 2018;174:134-144. Verhoeven RS, Burke, J, Schiffman, R. Nonclinical Pharmacokinetics and Pharmacodynamics of Brimochol, a Combination Product for the Treatment of Presbyopia. Investigative Ophthalmology & Visual Science June 2022, Vol.63, 1819 – F0435. https://iovs-arvojournals-org.libproxy1.nus.edu.sg/article.aspx?articleid=2780074 Ackerman, S. L., Torkildsen, G. L., Mclaurin, E., & Vittitow, J. L. (2019). Low‐dose brimonidine for relief of ocular redness: integrated analysis of four clinical trials. Clinical and Experimental Optometry , 102 (2), 131–139. https://doi-org.libproxy1.nus.edu.sg/10.1111/cxo.12846 Kubo C, Suzuki R. Involvement of prejunctional alpha 2-adrenoceptor in bovine ciliary muscle movement. J Ocul Pharmacol. 1992;8(3):225-31. Any product/brand names and/or logos are trademarks of Tenpoint Therapeutics.