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IYUZEH™ (latanoprost ophthalmic solution) 0.005%, the first and only preservative-free formulation of latanoprost, the most prescribed prostaglandin F2α analogue (PGA), is now available in the U.S. WALTHAM, Mass., Sept. 26, 2023 /PRNewswire/ -- Thea Pharma Inc. ("Thea"), the U.S. subsidiary of Europe's leading independent ophthalmic-focused pharmaceutical company, Théa, dedicated to the research, development, and commercialization of ophthalmic products, today announced the launch and availability of IYUZEH™ (latanoprost ophthalmic solution) 0.005% in the U.S. market. Preservative-free latanoprost, launched over ten years ago, is available in 46 countries, mostly under the brand name MONOPROST®, with about 1.5 million patients treated monthly.1 IYUZEH is the first and only preservative-free latanoprost for patients with primary open-angle glaucoma (POAG) and ocular hypertension (OHT) in the U.S. In randomized, controlled clinical trials of patients with POAG or OHT with mean baseline intraocular pressure (IOP) of 19-24 mmHg, IYUZEH lowered IOP by 3–8 mmHg compared to 4–8 mmHg by XALATAN®.2-4 Experience the full interactive Multichannel News Release here: "The U.S. launch of IYUZEH is a major step forward for Théa Group, the eye care community, and patients," said Jean-Frédéric Chibret, President of Théa. "Glaucoma is a chronic eye disease that affects the everyday lives of more than 60 million people globally. With IYUZEH now available, eye care providers can effectively treat their POAG and OHT patients with preservative-free latanoprost. I would like to thank everyone involved in achieving this milestone – including the providers and patients who participated in the clinical studies, our teams, and each of our partners – for helping us deliver on our commitment to enable patients access to medication without preservatives." "With the launch of IYUZEH in the U.S., Thea is responding to an important unmet need in the treatment landscape. IYUZEH brings similar efficacy of traditional latanoprost, formulated without preservatives, to help eye care providers confidently address their treatment goals of lowering intraocular pressure for people with POAG and OHT," said Susan Benton, President of Thea Pharma Inc. "We are thrilled to introduce IYUZEH and provide clinicians with an important new treatment option for their patients." "With the availability and proven efficacy of IYUZEH, it is now possible for eye care providers to lower elevated intraocular pressure in patients with POAG or OHT without preservatives on the ocular surface," said Jason Bacharach, M.D., Founder and Director of Research at North Bay Eye Associates in Petaluma, California. "This is a powerful option for our patients and for us, as treating clinicians." IYUZEH is available now through authorized distributors and the following wholesalers and order numbers: ABC (10282592), ANDA (603442), Cardinal (5865035), McKesson (2849651), NDC (82584-003-30). From enrollment to dispensing, Thea is committed to supporting eye care professionals and patients in every step of the access process. IYUZEH (latanoprost ophthalmic solution) 0.005% is now available for as little as $60 for a 30-day supply through programs with PhilRx® and the Thea Savings Card. For more information and eligibility requirements, please visit iyuzeh.com. PhilRx is a service that provides a convenient way to prescribe IYUZEH, with the medication shipped for free and directly to a patient's door. This service offers online and phone support for both eye care professionals and their patients. The Thea Savings Card is available to those commercially insured and not enrolled in a state or federally funded program. A patient may check their eligibility and activate this savings card at activatethecard.com/theasavingscard. Whether a physical or digital card, it can be utilized or redeemed at any retail pharmacy in the U.S. Thea is committed to helping patients have access to IYUZEH. A Patient Assistance Program is available for eligible U.S. patients that have a demonstrated financial need and are without prescription insurance coverage. With this program, we aim to allow every qualified patient the chance to see their treatment with eyes wide open. About IYUZEH™ IYUZEH™ (latanoprost ophthalmic solution) 0.005%, an opalescent, white to slightly yellow ophthalmic solution, is a topical formulation of latanoprost that is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). IYUZEH™ does not contain a preservative – it is the first and only preservative-free formulation of latanoprost, the most prescribed prostaglandin F2α analogue (PGA), in the United States. The recommended dosage of IYUZEH™ is one drop in the affected eye(s) once daily in the evening. If one dose is missed, treatment should continue with the next dose as normal. Reduction of the IOP starts approximately 3 to 4 hours after administration and the maximum effect is reached after 8 to 12 hours. IOP reduction is present for at least 24 hours. In the two clinical trials conducted with IYUZEH™ (latanoprost ophthalmic solution) 0.005%, the most frequently reported ocular adverse reactions were conjunctival hyperemia (34%) and eye irritation (19%) compared to XALATAN®, the preserved 0.005% latanoprost reference product which reported conjunctival hyperemia (37%) and eye irritation (31%). Healthcare providers, patients, and caregivers can learn more about IYUZEH at iyuzeh.com. INDICATIONS AND USAGE IYUZEH is a prostaglandin F2α analogue indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS Known hypersensitivity to latanoprost or any other ingredients in this product. WARNINGS AND PRECAUTIONS Pigmentation: Topical latanoprost ophthalmic products, including IYUZEH™ have been reported to cause changes to pigmented tissues. The most frequently reported changes have been increased pigmentation of the iris, periorbital tissue (eyelid), and eyelashes. Pigmentation is expected to increase as long as latanoprost is administered. The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. After discontinuation of latanoprost, pigmentation of the iris is likely to be permanent, while pigmentation of the periorbital tissue and eyelash changes have been reported to be reversible in some patients. Patients who receive treatment should be informed of the possibility of increased pigmentation. The long-term effects of increased pigmentation are not known. Iris color change may not be noticeable for several months to years. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts of the iris become more brownish. Neither nevi nor freckles of the iris appear to be affected by treatment. While treatment with IYUZEH™ can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly. Eyelash Changes: Latanoprost ophthalmic products, including IYUZEH™ may gradually change eyelashes and vellus hair in the treated eye; these changes include increased length, thickness, pigmentation, the number of lashes or hairs, and misdirected growth of eyelashes. Eyelash changes are usually reversible upon discontinuation of treatment. Intraocular Inflammation: IYUZEH™ should be used with caution in patients with a history of intraocular inflammation (iritis/uveitis) and should generally not be used in patients with active intraocular inflammation because inflammation may be exacerbated. Macular Edema: Macular edema, including cystoid macular edema, has been reported during treatment with latanoprost ophthalmic products, including IYUZEH™. IYUZEH™ should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema. Herpetic Keratitis: Reactivation of herpes simplex keratitis has been reported during treatment with latanoprost. IYUZEH™ should be used with caution in patients with a history of herpetic keratitis. IYUZEH™ should be avoided in cases of active herpes simplex keratitis because inflammation may be exacerbated. Contact Lens Use: Contact lenses should be removed prior to the administration of IYUZEH™ and may be reinserted 15 minutes after administration. ADVERSE REACTIONS The following adverse reactions have been reported with the use of topical latanoprost products: iris pigmentation changes, eyelid skin darkening, eyelash changes (increased length, thickness, pigmentation, and number of lashes), intraocular inflammation (iritis/uveitis), and macular edema, including cystoid macular edema. DRUG INTERACTIONS The combined use of two or more prostaglandins, or prostaglandin analogs including IYUZEH™ is not recommended. It has been shown that administration of these prostaglandin drug products more than once daily may decrease the IOP lowering effect or cause paradoxical elevations in IOP. For more information about IYUZEH™, please visit iyuzeh.com. For Full Prescribing Information, please visit . About Primary Open-angle Glaucoma The American Glaucoma Society states that glaucoma is a common ophthalmic disorder characterized by typical optic nerve damage and vision loss. It is most associated with elevated or dysregulated intraocular pressure, although there is evidence that other factors contribute to the disease.5 Glaucoma is a leading cause of irreversible blindness worldwide. Its prevalence in the U.S. is approximately 1,900 per 100,000 persons over age forty, and the condition is responsible for upwards of nine million clinic visits each year.6-8 In the U.S., where annual spending on optic nerve disorders is estimated at $5.8 billion annually,9 glaucoma is a significant public health concern. About Ocular Hypertension Mean IOP slowly rises with increasing age. Age older than 40 years is considered a risk factor for the development of OHT and POAG.10 OHT, a common condition, is a leading risk factor for the development of OAG.11 OHT is defined as IOP consistently greater than 21 mmHg (in at least one eye) and the absence of clinical signs of glaucoma.12 The risk of developing glaucoma increases with increasing IOP.13 Population studies such as the Framingham, Beaver Dam, Baltimore, Rotterdam, Barbados, and Egna-Neumarkt studies estimate that 4-10% of the population older than 40 years will have IOP levels of 21 mmHg or higher without detectable signs of glaucomatous damage. OHT has a 10-15 times greater prevalence than POAG.14 The use of topical IOP-lowering medications reduced the risk of glaucoma development from 9.5% in the control group to 4.4% in the intervention group.15 About Théa Laboratoires Théa is an independent pharmaceutical company specialized in the research, development, and commercialization of eye-care products. Based in Clermont-Ferrand, France, it has thirty-five affiliates & offices in Europe, North and South America, North Africa, and the Middle East. Today, its network includes nearly 1,900 employees, and its products are available in 75 countries around the world. In 2022, Théa had global revenues of approximately $941 million. The independent and family-owned and run group, founded from a Research and Development start-up by Henri Chibret, has been chaired since 2008 by Jean-Frédéric Chibret, his nephew. To learn more about Théa Group, visit . About Thea Pharma, Inc. Thea Pharma, Inc., is the United States subsidiary of Théa. Its product offering is comprised of a portfolio of seven leading eye-care products that are regulated or approved by the U.S. Food and Drug Administration (FDA), including Zioptan®, AcellFX™, Cosopt®, Cosopt® PF, Azasite®, Akten®, and Betimol®, iVIZIA™ dry-eye drops and eyelid hygiene products, and now IYUZEH™. By focusing our passion and expertise within the U.S. market, Thea Pharma's goal is to deliver uncompromising care that allows all stakeholders to envision the future of ophthalmic treatment with eyes wide open. To learn more about Thea Pharma, Inc., visit . References: Théa. Data on file. 2023. IYUZEH™ (latanoprost ophthalmic solution) 0.005%. Prescribing information. Thea Pharma Inc; 2022. Bacharach J, Ahmed IIK, Sharpe ED, Korenfeld MS, Zhang S, Baudouin C. Preservative-Free versus Benzalkonium Chloride–Preserved Latanoprost Ophthalmic Solution in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: A Phase 3 US Clinical Trial. Clin Ophthalmol. 2023;17:2575-2588. . Rouland JF, Traverso CE, Stalmans I, et al. Efficacy and safety of preservative-free latanoprost eyedrops, compared with BAK-preserved latanoprost in patients with ocular hypertension or glaucoma. Br J Ophthalmol. 2013;97(2):196–200. doi:10.1136/bjophthalmol-2012-302121. The American Glaucoma Society (AGS). Unmet needs in the detection, diagnosis, monitoring, treatment, and understanding of primary open angle glaucoma. 2021; 11. . Accessed March 1, 2023. Friedman DS, Wolfs RC, O'Colmain BJ, et al. Prevalence of open-angle glaucoma among adults in the United States. Arch Ophthalmol. 2004;122(4):532–538. doi:10.1001/archopht.122.4.532. Schappert SM. Office Visits for Glaucoma: United States, 1991-92. Vital and Health Statistics, Centers for Disease Control and Prevention / National Center for Health Statistics. 1995; March, No. 262. Lee PP, Walt JG, Doyle JJ, et al. A multicenter, retrospective pilot study of resource use and costs associated with severity of disease in glaucoma. Arch Ophthalmol. 2006;124(1):12–19. doi:10.1001/archopht.124.1.12. Wittenborn JS, Zhang X, Feagan CW, et al. The economic burden of vision loss and eye disorders among the United States population younger than 40 years. Ophthalmology. 2013;120(9):1728–35. . Leske MC, Connell AM, Wu SY, et al. Distribution of intraocular pressure. The Barbados Eye Study. Arch Ophthalmol. 1997 Aug. 115(8):1051-7. Kass MA, Heuer DK, Higginbotham EJ, et al. Assessment of Cumulative Incidence and Severity of Primary Open-Angle Glaucoma Among Participants in the Ocular Hypertension Treatment Study After 20 Years of Follow-up. JAMA Ophthalmol. 2021;139(5):558–566. doi:10.1001/jamaophthalmol.2021.0341. Burr JM, Botello-Pinzon P, Takwoingi Y, Hernandez R, Vazquez-Montes M, Elders A, et al. Surveillance for ocular hypertension: an evidence synthesis and economic evaluation. Health Technol Assess. 2012;16(29):1-271, iii-iv. Burr JM, Mowatt G, Hernandez R, Siddiqui MAR, Cook J, Lourenco T, et al. The clinical effectiveness and cost-effectiveness of screening for open angle glaucoma: a systematic review and economic evaluation. Health Technol Assess. 2007;11(41):iii-iv, ix-x, 1-190. Chihara E. Assessment of true intraocular pressure: the gap between theory and practical data. Surv Ophthalmol. 2008 May-Jun. 53(3):203-18. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: A Randomized Trial Determines That Topical Ocular Hypotensive Medication Delays or Prevents the Onset of Primary Open-Angle Glaucoma. Arch Ophthalmol. 2002;120(6):701-713. doi:10.1001/archopht.120.6.701. PRC-IYZ-1676-v2 SOURCE Thea Pharma Inc.

2023年6月30日，Bausch+Lomb博士伦（以下简称：B+L）宣布以17.5亿美元收购Xiidra立他司特和Novartis的其他眼科资产。B+L在获得Miebo的FDA批准后不久又收购了Xiidra，表明了品牌处方干眼病治疗产品的市场依然活跃。实际上，B+L正在打造一个完整的干眼症产品组合。除了Meibo和Xiidra，他们还从强生收购了Blink人工泪液。Meibo适用于蒸发性/睑缘腺功能障碍患者，Xiidra适用于更具炎症和缺液性的患者，Blink人工泪液则是目前最普遍的干眼症缓解手段。这系列布局也再次证明干眼病不仅仅是一种疾病，而是由一个或多个并发症构成的疾病，每个并发症都必须单独处理才能达到可接受的临床结果。   影响全球3.85亿人，发病年龄正在降低干眼症(DED)，也称为干眼综合征(DES)、干燥性角膜结膜炎(KCS)和干燥性角膜炎，是眼表泪膜异常和眼表炎症引起的多因素、进行性障碍。据估计，全球范围内干眼病影响约3.85亿人，超过5%全球人口。（Gayton，2009）。一般来说，干眼病的发病率随着年龄增加而增加（Bron等，2017）。在美国，估计超过320万50岁以上女性和170万50岁以上男性患有干眼病，预计到2030年患病人数将增加40%（Schaumberg等，2009；Schaumberg等，2013）。但近年来研究发现，干眼病的发病年龄正在降低。随着手机、手持电脑和阅读设备的广泛使用，使得年轻群体的患病率不断增加。并且，含苯扎氯铵防腐剂的青光眼滴眼液也可能造成加重干眼病症状的副作用。这一影响也不容小觑，随着人口老龄化，全球青光眼患者数量将接近8000万人（Quigley和Broman，2006）。Growth Plus Reports估计，由于干眼症创新药物技术进步、新型诊断工具的开发以及干眼病负担的增加，干眼病市场预计将以超过5%的年均复合增长率增长，到2030年将达到89.2亿美元全球市场。干眼症的治疗方案（图片来源：艾威药业）干眼症的治疗需要根据不同分型以及不同病程阶段进行方案匹配。目前的药物疗法包括补充人工泪液、局部使用糖皮质激素眼液及眼膏、局部使用免抑制剂、刺激泪腺分泌药物，或是通过手术手段治疗，其中最常搭配的治疗药物就是人工眼泪。由于大部分人工眼泪属于OTC类药物，人们可以自行前往药店购买，这也让人们往往忽略了对干眼症疾病严重性的认知。事实上，我们目前依旧缺乏一款能够解决这类多因素疾病，且对大部分患者能够快速起效的处方药。IVW-1001：眼睑涂抹给药，用药一周起效据动脉网统计，目前全球有超过45家企业正在开发治疗干眼症的药物，探索干眼症治疗方法50+种。但是由于干眼症是一种多因素眼表疾病，只有部分患者对目前市场上的产品有疗效。世界范围内，医药企业对于干眼症领域的关注源于上个世纪90年代。1995年，日本Santen Pharmaceutical （参天制药）开发的爱丽滴眼液获批上市，其高额的销售量快速带动了干眼症市场的发展，使干眼症作为独立的细分领域从眼科领域被划分出来。此后10年，Alcon/诺华、博士伦等眼科巨头公司纷纷加入竞争对人工泪液的成分和剂型进行优化推出下一代产品。其中，Alcon早期开发的盐酸四氢唑啉滴眼液Systane依旧强势，在2017年几乎垄断欧洲干眼症市场，而美国市场因为有新型作用机制药物的不断上市形成了现有“三足鼎立”的格局。2002年，Allergan（现为艾伯维）开发的0.05%环孢素制剂Restasis，在临床实验中以微弱的优势在美获批上市，打破了中重度干眼症无有效药物的空白局面。作为此类适应症的一线用药也是当时唯一的治疗品种，环孢素以其独特的免疫抑制机制成为美国干眼症市场的主流产品。在销售峰值时期可以每年为Allergan带来超过14亿美元的收入。随后，另一抗炎小分子药物Xiidra经由Shire研发于2016年进入市场。Xiidra凭借着起效时间更快这一优点迅速抢占Restasis的市场份额。近期，干眼症治疗出现一种新的治疗靶点——TRPM8受体激动剂。来自临床研究的证据表明，局部TRPM8激活可刺激泪腺功能，减少了DED患者的眼部不适并增加了泪液分泌。目前全球只有Alcon爱尔康和IVIEW艾威药业（以下简称：艾威药业）两个公司分别在进行这个新靶点药物的研发。Alcon的AR-15512滴眼液中的活性成分是一种专有的瞬时受体电位melastatin 8（TRPM8）冷热感受器的小分子选择性激动剂，目前，该药物正处于治疗干眼症的III期开发阶段。艾威药业的IVW-1001是一种高效且高选择性的TRPM8激动剂，局部用药后增加神经活动，通过三叉神经的眼神经（V1）向中枢神经系统传递产生清凉舒爽感觉，信号并进一步脑干输出至泪腺促进基础泪液的分泌（以增加眼表湿润度），另一方面冷却感本身可以减少眼部不适和眼部疼痛而缓解干眼病的症状。与传统滴眼液不同，IVW-1001是通过在眼睑部位擦拭给药，可以使药物能够透过真皮表面有效穿透到眼睑，最终到达眼表组织（角膜）中的通道位置。这一新型给药方式，让该创新药物关系有了更多元的差异化优势。首先是规避了滴眼液只有小部分药物能够进入组织，大部分则在一分钟内通过鼻泪管排出的固有问题。相比较而言，眼睑给药能够创造药物缓释的条件，使得药物更长时间作用在眼部，进而也减少了给药频率（预计单日仅需两次给药），提高使用的便利性。同时，该给药方式对于年长患者、手部灵活性较差的患者、佩戴角膜接触镜的患者以及白天需要佩戴假睫毛或化妆的患者等人群来说，都是优于传统滴眼药的用药形式。更重要的是，根据艾威药业的研究，该药物对应的靶点在人体眼睑下方的数量更高，通过缓慢穿透眼睑给药将会是更直接更精准的给药途径。在韩国开展的概念验证临床试验（POC）数据显示，IVW-1001用药一周即起效，可快速促进泪腺分泌泪液，从而直接对症治疗，明显改善患者症状。公司的目标是在2024年初启动针对干眼症患者的I/II期临床试验。纳入医保是提高疾病意识的有效手段艾威药业IVIEW Therapeutics Inc. 于2015年底在美国宾州成立，由制药行业资深人士梁波博士和John J. Baldwin博士创立，旨在通过开发创新眼科疗法以改善患者视力。梁波博士曾任职Pharmacopeia公司资深科学家，2006年和两个眼科医生在美国纽约创立CLS制药公司。他们发明的创新眼药于2015年被Shire夏尔制药公司以3亿美元现金收购。John J. Baldwin博士在默克公司的30年开发出众多创新药，包括治理青光眼的Trusopt，以及Cosopt、Pepcid AC等。他还是上海药明康德和上海华领医药的创始人，是入选美国化学会药物化学名人堂的床新药研发专家。艾威药业目前在美国和中国均组建起全职创新药物研发团队，在美国新泽西州拥有1万英尺的研究中心，在中国珠海横琴也有近1000平方的研究中心。公司的眼科药物开发顾问团队均在自诺华、辉瑞、GSK、爱尔康等大型药企拥有超过25年眼科药物开发经验，同时还配备了来自NIH、斯坦福大学、杜克大学、伯克利大学、哥伦比亚大学、默沙东等科研机构和药企的知名制药专家、科学家和眼科医生组成的SAB顾问委员会。同时与UNC Chapel Hill眼科系、复旦大学药学院、湖南师范大学医学院等合作建立创新研究中心，并设有专注“滴眼液往眼后部递送技术”的博士后流动站分站。公司自建的临床团队覆盖了首席医疗管、医学总监、临床运用、CRA、临床统计等职务，以便于能够更高质高效的和临床CRO合作开展国内相关临床试验。对于拥有丰富海外临床经验和FDA沟通经验的艾威团队来说，进入中国市场具备一定的基础优势，但也有许多特殊挑战需要克服。一方面，国内临床试验的启动周期更长、审核机构更多。另一方面，与欧美市场不同，我国对干眼症的治疗还停留在使用人工泪液，对于治疗中重干眼症的药物，国内市场处于空白阶段。更重要的是，患者与医生对干眼症的认识还相对欠缺，对防止疾病发展恶化而接受处方药治疗的意识相对薄弱。如何让干眼症患者大规模的从购买OTC药物到接受处方药治疗，艾威药业联合创始人兼董事长兼首席执行官梁波博士认为，纳入医保将会是扭转这一局面的最有效途径。因此，加大与有关部门和监管机构的沟通，通过促进医保谈判的成功来推动市场教育，将会是艾威药业未来的努力方向之一。海外多元商业合作，国内加快商业化进程眼科在医药行业虽然是专科领域，但眼科疾病覆盖范围广，患者基数高，加上随着电子产品的利用率越来越高，人口老龄化的社会现象，眼科疾病的增长趋势越来越高。我国过去六年间仅有七款眼科新药上市且均为进口产品，临床上眼科治疗药物的远远未满足临床的需求，因此，眼科药物行业急需创新的，具有更好疗效，可以填补市场对眼科药物的需求。这两三年来，国内外机构在加大了眼科创新药物研发的投入，也拓宽了眼科治疗法的思路，有小分子药物、不同的治疗机理、基因治疗法、抗体类药物；多种创新型眼部给药递送系统的研发，突破了传统眼部给药的局限性，也显示良好的市场前景。未来，艾威药业在加快创新产品开发的同时，将致力于将现有产品管线临床开发加快推进，拟进入和大公司合作和商业化阶段。公司的IVIEW-1201治疗病毒性结膜炎和细菌性结膜炎临床II期实验都将于2023年底完成，在临床数据的支持下，公司将在2024年推进临床III期，同时相关商务拓展将同时展开。治疗干眼症创新化合物IVW-1001在2024年展开临床IIa实验验证安全性和疗效。此外，公司还将同步进行治疗近视眼创新化合物（计划2024年向FDA提交PIND申请）和治疗青光眼创新基因治疗法的开发（2024年上半年启动IIT临床）。艾威药业的目标是成为一个专注眼科创新药和创新疗法开发，具有全球竞争力的生物技术公司。应用团队在中美的优势，未来将继续拓展海外市场的合作开发、商业授权、License out等商业合作，并加快推进中国市场的商业化进程。近期推荐声明：动脉网所刊载内容之知识产权为动脉网及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。动脉网，未来医疗服务平台