Comparison of fractional co2 laser therapy alone and with its combination with topical timolol or topical insulin in the treatment of acne scar, A randomized controlled clinical trial

开始日期2023-12-31

申办/合作机构

Shiraz University of Medical Sciences

NCT06140186 / Recruiting临床3期

Efficacy and Safety of add-on Topical Timolol in the Management of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor-induced Paronychia: A Prospective Randomized Open-labelled Trial

This study would assess the clinical efficacy of add-on topical timolol 0.5% gel to betamethasone valerate 0.1% for the treatment of EGFR-TKI induced paronychia. Eligible patients, who develop paronychia (affecting fingernails, toenails or both), will be included in this study. They will be randomized in 1:1 ratio using computer-generated randomization list to receive either combination of topical timolol 0.5% gel and betamethasone valerate 0.1% lotion application twice daily or betamethasone valerate 0.1% lotion application twice daily. Patients in timolol combination treatment group will receive topical timolol 0.5% gel twice daily with occlusion (i.e. covered with adhesive badge) and betamethasone valerate 0.1% lotion twice daily with occlsuion for 1 month. Patients in routine arm would receive the management according to routine clinical practice, including prescription of betamethasone valerate 0.1% lotion twice daily for 1 month with occlusion. For patients who do not have paronychia completely resolved after 4 weeks, the treatment assigned will be continued for another 4 to 8 weeks , up to 12 weeks to see the effect.

开始日期2023-04-01

申办/合作机构

Queen Mary Hospital

NCT06321562 / Recruiting临床1期

A First-In-Human, Open-Label, Dose Escalating, Non-Randomized Study to Assess the Safety and Tolerability of a New Timolol Sustained Release Intraocular Implant (TimoD) in Subjects With Primary Open Angle Glaucoma With Pseudophakia

The purpose of this study is to test a new method to deliver an approved medicine called Timolol in the eye of participants with glaucoma and pseudophakia. The main questions it aims to answer are how safe the investigational drug is and how the body tolerates it.
The study will also check:
how safely the implant is placed in and removed from the eye and how the body responds to the procedure,
how safe different doses of timolol are and how the body handles taking it,
the amount of Timolol released in the bloodstream,
if there is any positive effect on the pressure inside the eye.

开始日期2023-03-01

申办/合作机构

EyeD Pharma SA

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100 项与噻吗洛尔相关的转化医学

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100 项与噻吗洛尔相关的专利（医药）

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项与噻吗洛尔相关的文献（医药）

2024-02-23·BMC pediatrics

Rare complication - skin atrophy - after systemic conservative therapy of infantile hemangioma.

Article

作者: Konstantine Chakhunashvili ; Eka Kvirkvelia ; Natia Todua ; Davit G Chakhunashvili

BACKGROUND:

Hemangiomas, also called infantile hemangiomas (IH) or hemangiomas of infancy are the most frequently seen benign vascular tumors of infancy. Different types of hemangiomas are described in the literature. The current approach is to assess the risk and, if needed, first line treatment is to initiate systemic propranolol.

CASE PRESENTATION:

A 3-month-old Caucasian female patient was brought as an outpatient. The main complaint was an infantile hemangioma in the facial area, which as per the parents' story appeared within a week of birth like a small reddish line and it rapidly grew. Systemic propranolol was proposed as a first-line treatment and the adverse effects were explained. The parents, afraid of the side effects, wanted to explore other possibilities such as topical timolol, however, since it had no effect, propranolol was initiated in the end. Hemangioma was completely reduced in size; however, a skin defect was detected. As per the dermatologist's counsel, topical cream was initiated. The skin defect was reduced but not fully healed. The child is still being monitored periodically.

CONCLUSION:

After successful treatment of hemangioma, we identified a skin defect, which was very similar to steroid-induced skin atrophy. However, we cannot attribute this to a single factor. The only thing that can be concluded is that the subject needs a thorough studying, since rate of infantile hemangioma is high, and pediatricians need a clear management strategy of how to approach skin atrophy after successfully treating the hemangioma itself.

2024-02-21·American journal of ophthalmology

Omidenepag Isopropyl Versus Timolol in Patients With Glaucoma or Ocular Hypertension: Two Randomized Phase 3 Trials (SPECTRUM 4 and 3).

Article

作者: Jason Bacharach ; Jacob W Brubaker ; David G Evans ; Fenghe Lu ; Noriko Odani-Kawabata ; Takaharu Yamabe ; David L Wirta

PURPOSE:

The SPECTRUM 4 and 3 studies assessed the intraocular pressure (IOP)-lowering efficacy and safety of omidenepag isopropyl (OMDI) 0.002% vs timolol 0.5% in patients with glaucoma or ocular hypertension (OHT).

DESIGN:

Phase 3, randomized, controlled, double-masked, noninferiority studies.

METHODS:

Multicenter studies in the US. Inclusion criteria for adults ≥ 18 years (SPECTRUM 4 [N=409] and 3 [N=413]) were open-angle glaucoma or OHT, and IOP ≥ 22 mm Hg and ≤ 34 mm Hg; and for pediatric patients < 18 years (N=13, SPECTRUM 3) were pediatric glaucoma or OHT. The primary objective in both studies was OMDI noninferiority to timolol in reducing IOP (3 months). SPECTRUM 3 included an additional 9-months of OMDI treatment. Safety evaluations were of ocular/non-ocular adverse events (AEs).

RESULTS:

The IOP-lowering range of OMDI remained consistent in SPECTRUM 4 and 3 (-5.6 to -5.9 vs -5.3 to -5.7 mm Hg, respectively); however, timolol efficacy varied (-5.4 to -6.1 vs -6.4 to -7.0 mm Hg, respectively). OMDI noninferiority was achieved in SPECTRUM 4. Efficacy was maintained with 12-month treatment in SPECTRUM 3. Both studies reported more ocular AEs with OMDI, but lower rates of appearance-altering AEs vs timolol. No new safety concerns were identified. Rates of macular edema in pseudophakic patients increased with prolonged OMDI exposure.

CONCLUSIONS:

SPECTRUM 4 and 3 demonstrated consistent 3-month IOP-lowering efficacy and safety of OMDI vs timolol in patients with glaucoma or OHT. The 12-month data from SPECTRUM 3 suggest OMDI may have long-term benefits in patients with glaucoma or OHT.

2024-02-20·International ophthalmology

The effect of combination therapy with intravitreal bevacizumab and topical timolol-dorzolamide eye drops on diabetic macular edema: a double-blind randomized controlled trial.

Article

作者: Sahba Fekri ; Ali Rabiei ; Sadid Hooshmandi ; Hosein Nouri ; Seyed-Hossein Abtahi

BACKGROUND:

The mainstay of treatment in diabetic macular edema (DME) is intravitreal administration of anti-vascular endothelial growth factors (anti-VEGFs). Aqueous depressants may enhance the effects of anti-VEGF agents by prolonging their clearance via aqueous outflow.

PURPOSE:

To compare the anatomical and functional outcomes of treatment with intravitreal bevacizumab (IVB) and topical timolol-dorzolamide versus IVB alone.

METHOD:

In this randomized placebo-controlled clinical trial, patients with center-involving DME (ci-DME) and best corrected visual acuity (BCVA) of 20/30 or less were enrolled and randomly allocated to two treatment arms. One group received three monthly IVB injections and timolol-dorzolamide eye drops twice a day (IVB + TD group); the other group received three monthly IVB injections and artificial tear drops as placebo (IVB group). Patients underwent ophthalmic evaluations and macular optical coherence tomography scans at baseline and 1 month after the third injection.

RESULT:

Forty-six eyes from 46 patients with ci-DME were recruited. There was no intergroup difference regarding age, gender distribution, diabetic retinopathy stage, glycemic indices, BCVA, central macular thickness (CMT), or intraocular pressure at baseline. BCVA was significantly improved in the IVB + TD group (0.46 ± 0.18 to 0.36 ± 0.18 logarithm of the minimum angle of resolution [logMAR], p = 0.002), in contrast to IVB group (0.40 ± 0.17 to 0.35 ± 0.22 logMAR, p = 0.113). Similarly, the IVB + TD group showed a significant reduction in CMT (p < 0.001), unlike the IVB group (p = 0.086); and the CMT change in the former was greater than in the latter (- 0.57 ± 57.67 vs. - 25.52 ± 68.02 μm, p = 0.033).

CONCLUSION:

Our findings support the short-term effectiveness of topical timolol-dorzolamide as adjunctive therapy to IVB injections in managing center-involving DME in terms of anatomical and visual outcomes.

TRIAL REGISTRATION:

Clinicaltrials.gov NCT05083689 (October 19, 2021).

项与噻吗洛尔相关的新闻（医药）

2024-03-21

·PRNewswire

Landmark Non-inferiority Clinical Trial Demonstrates Nanodropper's Positive Impact on Glaucoma Treatment

A new study published in Ophthalmology demonstrated no clinically significant difference in IOP with microdrops with the Nanodropper® Adaptor versus conventional eyedrops of the glaucoma treatment timolol maleate 0.5%. ROCHESTER, Minn., March 21, 2024 /PRNewswire/ -- Nanodropper, Inc., an ophthalmic device company that created the eyedrop volume-reducing Nanodropper® Adaptor, announced today that its clinical trial "An Evaluation of the Efficacy and Safety of Timolol Maleate 0.5% Microdrops Administered with the Nanodropper" was published in the journal Ophthalmology. Continue Reading This was a prospective, multicenter, randomized, parallel-group, single-masked, active-controlled, non-inferiority trial. The trial enrolled glaucoma patients and demonstrated there was no clinically significant difference in the intraocular pressure (IOP)-lowering effects of microdrops administered with the Nanodropper Adaptor compared to conventional eyedrops of timolol, an eyedrop medication commonly used to treat glaucoma. This was observed at all time points throughout the eight-hour study. Subjects in the microdrops arm also experienced a significantly smaller decrease in heart rate compared to those that received conventional drops, demonstrating there could be an enhanced safety profile of using a microdrop of timolol compared to a conventionally-sized eyedrop. Landmark Non-inferiority Clinical Trial Demonstrates Nanodropper's Positive Impact on Glaucoma Treatment Post this "We are thrilled, albeit not surprised, by these encouraging results demonstrating the Nanodropper Adaptor's capacity to improve patient safety," said Jenny Steger, PhD, Chief Scientific Officer of Nanodropper. "Thousands of eyecare clinics in the U.S., and tens of thousands of patients worldwide, are already utilizing the Nanodropper to great effect. This study reflects the benefits these patients have been experiencing." The Nanodropper Adaptor is the first and only sterile adaptor for eyedrop bottles that reduces eyedrop volume to just what the eye can absorb, significantly reducing medication waste and financial barriers for patients and clinics. This study's results suggest the Nanodropper Adaptor's microdrops provide patients an enhanced safety improvement over conventional eyedrops while maintaining the efficacy of the medication. "Eyedrop size has not seriously been commercially addressed in the past," said Alan L. Robin, MD, corresponding author on the publication and a global leader in glaucoma research and treatment for decades. He is a charter member of the American Glaucoma Society, its first executive vice president, and sits on Nanodropper's Medical Advisory Board. His previous research on microvolume delivery of eyedrops directly inspired the creation of the Nanodropper Adaptor. "I believe microvolume delivery technologies may offer solutions in the form of less waste, increased patient savings, and hopefully better safety profiles for many topical ophthalmic medications," said Dr. Robin. "Nanodropper is the first commercially available potential solution to this long-standing problem." To review the study in Ophthalmology, the full-text version can be viewed at this link. Where are Nanodropper Adaptors available? Nanodroppers are available at , and in over 2,500 eyecare clinics across all 50 states, Puerto Rico, and the U.S. Virgin Islands. Nanodropper Adaptors have also been made available via the company's Give the Gift of Vision charitable program to U.S.-based patients who cannot afford to purchase one, and internationally through more than a dozen nonprofit partners providing access to eyecare on a global scale. Contact: Mackenzie Andrews [email protected] SOURCE Nanodropper

临床结果

2024-03-21

·PRNewswire

OcuMension (01477.HK) Invests Over RMB 123.8 Million in Research, Technology and Self-development Progress in Tandem, Main Product Sales Show Comprehensive Growth

SHANGHAI, March 21, 2024 /PRNewswire/ -- On the evening of March 21st, OcuMension Therapeutics (Shanghai) Co., Ltd. (01477.HK, hereinafter referred to as "OcuMension" or the "Company") disclosed its 2023 annual performance report. The company achieved a total operating income of RMB 246.4 million for the full year, a year-on-year increase of 55.0%; with a comprehensive gross profit of RMB 144.4 million, representing a year-on-year increase of 40.3%. During the reporting period, the company's major operating indicators performed well, benefiting from rapid growth in sales revenue and further improvement in operational efficiency and cost control. Enhanced Product Matrix, Rapid Expansion Leveraging First-mover Advantage Adhering to the development philosophy of "providing world-class holistic solutions for pharmaceuticals," OcuMension has consistently devoted itself to identifying, developing, and commercializing innovative or best-in-class ophthalmic therapies. The company continuously enriches and expands its product matrix to meet the significant demand gap in Chinese ophthalmic medical care while maintaining its leading position in the ophthalmic track. A diversified product matrix has laid the foundation for the company's steady growth. Leveraging its strong corporate strength, the company possesses a leading ophthalmic pharmaceutical platform with various drugs for both anterior and posterior segments, providing strong support for the company's development. Among them, the company's main products such as Ouqin (sodium hyaluronate eye drops), Emidin (timolol maleate eye drops), and Shilida (latanoprost eye drops) have all maintained steady growth. Additionally, as one of OcuMension's outstanding products, OT-401(YUTIQ)® for the treatment of chronic non-infectious uveitis was successfully included in the medical insurance catalog in December of last year. It is reported that OT-401(YUTIQ)® completed the first domestic injection in December 2022, breaking the deadlock in the treatment of uveitis in China at that time, filling the treatment gap domestically, alleviating the burden on patients to the greatest extent, and marking the formal entry of the product into ophthalmic clinical applications. It is worth noting that since OT-401(YUTIQ)® officially entered the medical insurance catalog on January 1st of this year, the company has rapidly promoted its medical insurance landing work nationwide with its comprehensive commercialization capabilities, bringing better and more affordable treatment options for uveitis patients. As of the disclosure date of the report, the terminal injection volume of OT-401(YUTIQ)® has exceeded the total for the previous year and is expected to continue to rapidly expand. Overcoming Technological Peaks, Strengthening Self-defense with R&D Strength To break the previous dominance of foreign capital in the Chinese ophthalmic drug market, the company continues to increase its investment in research and development, focusing on dual-source innovation, optimizing registration and development, promoting commercialization, and adhering to high-quality technical standards throughout the entire production cycle to ensure product safety, efficacy, and quality control. With years of technological accumulation and industrial experience, in 2023, the company achieved several milestone breakthroughs with the assistance of clinical PI, including the submission of NDA for OT-1001 (timolol hydrochloride eye drops) accepted by CDE and included in the priority review program; completion of global patient enrollment for Phase III MRCT of OT-101 (atropine sulfate eye drops); completion of real-world studies for OT-502 (dexamethasone implant), currently in the Pre-NDA stage; the completion of patient enrollment for Phase II clinical trials of OT-202 (tyrosine kinase inhibitor), a self-developed drug for dry eye syndrome, in 25 experimental centers, with a total of over 700 patients enrolled during the year. This not only enriches the company's product pipeline but also provides more high-quality treatment options for patients. The edge of technology stems from the strength of research and development behind it. Throughout 2023, the company invested a total of RMB 123.8 million in research and development, injecting strong momentum into the company's continued development. Meanwhile, the company also focuses on building a clinical research platform and constructing a research and development team to enrich the company's product pipeline and produce multi-level products that better meet patient needs. So far, the company has a total of 25 drug assets for both anterior and posterior segments, with 12 products already commercialized, covering both anterior and posterior segments and forming a strong product matrix in the fields of anti-allergy and glaucoma. Among them, five products in the company's pipeline are still in Phase III clinical trials, making it one of the companies with the highest number of Phase III clinical trials for innovative drugs in the Chinese ophthalmic drug market. It is noteworthy that the company has made breakthrough progress in the research and development of the myopia drug Atropine recently. Faced with the challenge of stability, the company cleverly solved the long-term storage stability problem of low-concentration atropine sulfate solution by using a dual-chamber device of reconstitution solution and freeze-dried powder. Currently, the company's self-developed product OT-101-S (0.01% and 0.05% atropine sulfate eye drops) has had its Phase III clinical trial application accepted by CDE in China. Accelerated Commercialization Process Provides Strong Support for Sales Revenue on the Sales Side As one of the powerful driving forces for terminal sales, commercialization has also shown remarkable performance for OcuMension in terms of product hospitalization. In 2023, with a complete product pipeline, the company continued to expand hospital coverage and accelerate product hospitalization. Currently, the company has formed a nationwide sales network, covering 1558 tertiary hospitals, with a commercial team of over 230 people. On this basis, the company deeply explores the commercial penetration of strong products such as Shilida and Emidin, achieving rapid growth in sales revenue. In addition, under the full play of national fiscal funds' guiding role in the development of innovative drugs, more approval resources will tilt towards high-value innovative drugs. With the company's increasingly mature commercialization process and the policy-driven tailwind, the company's image in the secondary market, previously underestimated, is expected to change. Within the month, the Hong Kong stock innovative drug sector has seen a full-scale increase, and the company gradually returned to a benign growth track in this round of valuation restoration of Hong Kong stock pharmaceuticals. In the future, driven by multiple factors such as aging, electronic lifestyle, increasing medical awareness among patients, and rising resident payment levels, China's ophthalmic market has tremendous development potential. The company will rely on its first-mover advantage to rapidly enhance its competitiveness and penetration in the domestic market, while actively expanding overseas markets to enhance the company's international influence. By continuously deepening hospital cooperation, optimizing sales network layout, the company will further improve product coverage, providing more patients with high-quality and efficient medical services. Chasing light and encountering, forging ahead. The development of innovative drugs in the field of Chinese ophthalmology is arduous but promising. With the continuous improvement in market recognition of the company's products, OcuMension will continue to uphold the development philosophy of innovation-driven and quality-oriented, continuously strengthen research and development investment, introduce more innovative and competitive products, strive to lead the market, and provide greater returns for investors. SOURCE OcuMension

临床3期财报申请上市

2024-03-12

·药渡

一场教科书式的自救：从被放弃的“分子”，到创收百亿

无论是big parma还是biotech，砸钱做研发是每家药企都必须会做的事，但其中的先后次序、轻重缓急，是一门学问。在创新药领域，前期数据亮眼，后期翻车的故事屡见不鲜；而如何通过一系列运作，将一手烂牌打好的故事，也不少见。艾尔建眼科药物ALPHAGAN研发迭代的故事，可能是关于后者最好的诠释之一。众所周知，创新药的竞争，本质是专利竞争。专利保护了相应的分子结构（化学药）或是氨基酸序列结构（生物药），使得其他药企在专利保护期内不能仿制，从而获得高额回报。而ALPHAGAN上市之初，溴莫尼定的核心化合物专利已经到期，仅有5年的新化合物实体独占期。一款如此“短命”的产品，显然与艾尔建10年的投入，不成正比。但是，医学的未来是没有剧本的。一个被放弃的分子，在艾尔建手里起死回生；一款“短命”的产品，也有可能继续逆袭。产品上市之后，艾尔建又通过10余年的持续研发、四次产品迭代以及一系列的专利布局，将ALPHAGAN发展成其眼科药物当家花旦：在上市20年后，依旧能为艾尔建贡献5亿美元的销售额，2016年至今累计创收就已超百亿人民币。/ 01 /一个被放弃的分子ALPHAGAN的故事，要从上世纪60年代说起。Warner-Lambert（后被辉瑞收购）开发了一种新的肾上腺素α2-受体激动剂，溴莫尼定，并对它在治疗高血压类疾病方面的效果寄以厚望。肾上腺素受体分为α受体和β受体，α受体又分为α1受体和α2受体。其中，α2受体广泛存在于神经突触前膜，兴奋时可反馈性减少去甲肾上腺素的释放，起到与肾上腺素受体抑制剂相同的作用。但在后续10多年的实验研究中，溴莫尼定的表现总是令人失望。屡屡受挫的Warner-Lambert，在1985年前后决定放弃这个项目，以发表文章、公布实验结果的方式，为溴莫尼定画上一个句号。在这一文章中，被公开的还包括溴莫尼定可用于治疗眼部疾病的潜在可能。靠滴眼液起家的艾尔建，当时正在寻找能用于治疗青光眼的新化合物。眼内压升高是青光眼的主要症状，艾尔建的科学家看到Warner-Lambert发表的文章后，非常兴奋，认为溴莫尼定也许能够作为降低眼内压的滴眼药来局部使用。一直以来，对于青光眼的治疗主要是以降眼压为主，使视神经免受进一步损害。眼内的一些受体和酶是青光眼药物的作用对象，如肾上腺素受体、胆碱受体等。其中，肾上腺素受体在眼内分布广泛，存在于角膜、虹膜、泪腺等组织中。溴莫尼定作为选择性α2受体激动药，通过兴奋突触前α2受体，负反馈引起肾上腺素释放减少，能够抑制房水的生成和增加葡萄膜、巩膜外流，进而达到降眼压效果。尽管当时溴莫尼定的化合物专利保护期已经过半，但可能是出于对该化合物成药性的信心，艾尔建首先做的事情就是从Warner-Lambert手中购得专利独占许可权。但是，尽管有Warner-Lambert先前的研究基础，艾尔建仍然用了近10年的时间，才开发出一种眼用制剂ALPHAGAN，其中包含0.2%的酒石酸溴莫尼定作为活性成分。1996年9月，FDA批准ALPHAGAN作为滴眼液用于治疗青光眼。就这样，一个被放弃的分子，在艾尔建手里起死回生。但艾尔建却高兴不起来，因为溴莫尼定的化合物专利早在3年前，也就是1993年就已经过期。也就是说，ALPHAGAN上市之初，是一个没有专利保护的新药，其新手保护期只有新化合物实体（NCE）的5年独占期。在ALPHAGAN获批的5年内，FDA不能接受他人针对同个药物活性成分（即酒石酸溴莫尼定）的报批申请。但5年的市场独占期，对于艾尔建投入的时间与财力来说，显得过于微不足道。在这一背景下，艾尔建开启了一场关于产品迭代的自救及专利大作战。/ 02 /一场教科书式的自救任何一款新药都不可能是完美的，都是不断寻找疗效与安全性的平衡。面对ALPHAGAN的困境，艾尔建决定继续投入研究，在仿制药进入之前，对ALPHAGAN进行迭代升级，与此同时，寻求有效的专利保护。由此，一场长达10年的产品迭代研究开始了。在第一代ALPHAGAN中，一个不可忽视的问题在于，部分患者会对药物产生过敏反应。于是，艾尔建的第二代ALPHAGAN针对的便是这一痛点。2001年，改进后的第二代产品ALPHAGAN-P（0.15%）获得FDA批准上市。表面看，其与第一代产品相比，只是将活性成分酒石酸溴莫尼定的浓度，从0.2%降低至0.15%，但实际上，并非如此简单。二代产品使用羧甲基纤维素作为增溶剂来替代环糊精，并使用了一种新型防腐剂，稳定性二氧化氯。相比第一代产品，配方的改变，使得两代产品治疗效果相当，但ALPHAGAN-P（0.15%）却显著减轻了过敏的副作用。也正因此，ALPHAGAN-P（0.15%）一经上市并大卖，在上市后的2年时间里几乎占领了全部市场。更重要的是，艾尔建围绕ALPHAGAN-P（0.15%）进行了一系列的专利布局。基于后续的研究，艾尔建还递交了两个针对新用途的专利申请，分别涉及用溴莫尼定来保护视神经，以及用溴莫尼定来保护神经系统的用途和方法。而由于没有核心专利的保护，仿制药企早早便盯上了ALPHAGAN。2001年，有两家仿制药企，在ALPHAGAN独占期到期前一年就提交了ANDA申请，希望仿制ALPHAGAN。两年后，艾尔建在专利诉讼中败了下来，第一代ALPHAGAN的仿制药获批上市，但销售惨淡，因为艾尔建推出了更成功的二代产品。尽管二代产品商业化大获成功，2005年销售额已超3.5亿美元，也有了系列专利保护，但艾尔建并没有停下ALPHAGAN的迭代研究。艾尔建将酒石酸溴莫尼定的浓度进一步降低至0.1%，并于2005年获批上市。围绕第三代产品ALPHAGAN-P（0.1%），艾尔建同样进行了一系列新专利申请。比如新专利之一，保护的是一种降低眼内压的水溶性眼用组合物，即三代产品ALPHAGAN-P如何在实现活性成分含量降至0.1%，疗效维持不变的同时，副作用大大降低。继二代、三代产品的迭代升级，艾尔建还开发了包含溴莫尼定和噻吗洛尔两种活性成分的组合产品，这也可以看作是艾尔建围绕ALPHAGAN开发的第四代产品COMBIGAN（0.2%/0.5%），2007年获得FDA批准上市。这一次，艾尔建同样布局了多件专利，包括组合物本身及用药剂量等。新产品的推出和商业成功，不可避免地带来了新的挑战。但艾尔建通过其专利布局，扛住了山德士等仿制药企的一次次进攻。ALPHAGAN/COMBIGAN也由此成为艾尔建的眼科当家花旦。/ 03 /来自艾尔建的启示回看ALPHAGAN的发展历程，科学家的工作尤为重要，首先要想到把一个失败的抗高血压药物拿来治疗青光眼，之后再开发出意料不到的剂量和各个组合物。与此同时，药企如何通过专利保护，最大化自己的药物价值也颇为重要。1996年至2007年，11年间，ALPHAGAN/COMBIGAN逐渐发展壮大成为一个包括多款热销药品的眼科药物组合，且拥有20多件专利。也正因此，虽然错失核心化合物专利的保护，但艾尔建从组合物、配方、用药剂量等多个角度，对溴莫尼定系列产品设置了层层外围专利保护，经受住了一次次专利挑战和诉讼的考验。在上市20年后，依旧能为艾尔建贡献5亿美元的销售额。根据财报，2016年至今销售额接近40亿美元，一直是艾尔建的第二大眼科药品。在这个过程中，甚至不能放过任何对自己有利的条款，哪怕看上去作用并不大。比如，在第一代ALPHAGAN产品最初获批上市时，艾尔建还在NCE独占期基础之上，获得了儿科用药（PED）独占期，现有独占权期延长6个月。由此，将ALPHAGAN的NCE独占期延长至5.5年。看似仅仅半年的时间，也为艾尔建二代产品的推出赢得了宝贵的时间。这也提醒药企，钻研创新研发的同时，还要充分利用多项专利权以及专利权与非专利独占期的多重保护。实际上，艾尔建与ALPHAGAN的故事，更是体现了创新的重要性。而这种创新，不单单是从0到1的突破性创新，还要持续自我迭代，永远领先对手一步。福泰制药贵为千亿美金的Biopharma背后，本质也是其在历经失败之后，抓住囊性纤维化机会，疯狂迭代产品，革自己的命。作为囊性纤维化治疗领域的拓荒者，福泰制药同时也是颠覆者。首个治疗药物Kalydeco的成功后，其并没有止步于此，而是不断进行迭代，以保证更多更具竞争力的产品不断脱颖而出，疗效提升的同时，患者覆盖范围也不断扩大。无论是福泰制药这一千亿Biopharma的养成秘诀，还是艾尔建与ALPHAGAN的逆袭故事，都可以概括为一句话，在被别人颠覆前，先颠覆自己。这也体现了创新药研发的艰辛，即使经历九死一生成功上市，也不能一劳永逸地坐享收益，而是必须不断突破和持续创新。当然，ALPHAGAN的故事，也充分展现了创新的学问之精深。即使最初上市的产品没有任何专利保护，但后续进行积极的产品生命周期管理，加快产品迭代的步伐，辅以一系列新专利布局，也有可能将原本“短命”的产品变成称霸多年的销售明星。文／武月免责声明“药渡”公众号所转载该篇文章来源于其他公众号平台，主要目的在于分享行业相关知识，传递当前最新资讯。图片、文章版权均属于原作者所有，如有侵权，请及时告知，我们会在24小时内删除相关信息。微信公众号的推送规则又双叒叕改啦，如果您不点个“在看”或者没设为"星标"，我们可能就消散在茫茫文海之中~点这里，千万不要错过药渡的最新消息哦！👇👇

并购专利到期

100 项与噻吗洛尔相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D08600	噻吗洛尔	S01ED01 C07AA06	DB00373

研发状态

适应症	最高研发状态	国家/地区	公司
高血压	批准上市	美国更多	Thea Pharma, Inc. 更多
眼部疾病	临床2期	美国更多	Betaliq, Inc.初创企业更多
青光眼	无进展	-	Alcon Research Ltd. 更多

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03931317 (Pubmed \| Am J Ophthalmol) 人工标引	N/A	开角型青光眼 \| 高眼压症	50	Latanoprostene Bunod	襯構膚衊廠淵顧鹹壓鏇(繭壓廠選顧憲築襯夢顧) = 廠齋積網餘願獵衊鹽顧願憲衊築獵鹹醖鬱繭鏇 (鹽醖糧獵積鏇齋窪糧鑰 )	积极	2022-05-05
				Timolol	-
NCT02802137 (Pubmed \| Adv Ther) 人工标引	临床4期	开角型青光眼	43	Tafluprost+Dorzolamide+Timolol (Pftafluprost)	(鏇淵膚壓衊蓋鹹選夢夢) = 鑰憲鑰觸選觸醖憲簾繭窪構構製壓網鬱鏇繭艱 (鹹餘壓選齋蓋艱壓獵鹹, 3.9) 更多	积极	2017-01-01
				Dorzolamide+Timolol+Tafluprost (triple PF regimen)	鑰蓋餘鑰築壓糧鑰鬱襯(範齋觸選選繭積憲壓鏇) = 艱鏇淵壓糧壓蓋淵壓壓蓋鏇遞鹽願夢夢製憲構 (醖醖憲夢窪壓鑰選餘窪 )
NCT01217606 (Pubmed) 人工标引	临床3期	青光眼	185	Bimatoprost+Brimonidine+Timolol	(網範艱襯壓糧憲願鹽鏇): difference = -2.17 (95% CI, -3.12 ~ -1.22) 更多	优效	2020-02-01
				Brimonidine+Timolol
GC-010, GC-012 (ARVO2023)	临床3期	-	-	Travoprost intraocular implant (slow-eluting)	(廠鹹獵壓願蓋鹽廠鹹簾) = 3% of travoprost implant patients 簾窪餘範蓋蓋蓋壓願製 (淵齋觸鹹選艱選襯願範 ) 更多	积极	2023-04-23
				Topical timolol 0.5%
ASCO2021	N/A	毛细血管瘤	-	Topical timolol drops	(顧積簾壓願鹹積齋鹽積) = 5% 鬱淵網衊廠製顧壓積鏇 (艱築鬱廠襯鏇鹽醖窪觸 )	积极	2021-05-28
				Oral propranolol solution
EDEN consortium (ARVO2021)	N/A	-	106	Latanoprost	(醖醖夢糧夢憲願夢繭鑰) = 網繭夢襯廠築艱衊製淵餘窪齋蓋製鹹艱窪積願 (鬱鑰窪獵糧鬱簾積鹹鏇 )	不佳	2021-06-01
				Timolol	(醖醖夢糧夢憲願夢繭鑰) = 鹹壓餘鹽窪餘衊醖餘齋餘窪齋蓋製鹹艱窪積願 (鬱鑰窪獵糧鬱簾積鹹鏇 )
NCT01241240 (Pubmed \| J Ophthalmol) 人工标引	临床3期	高眼压症 \| 开角型青光眼 \| 青光眼	190	Bimatoprost+Brimonidine+Timolol	(夢憲鑰選範獵範觸鏇餘) = greater reduction 築顧獵構壓糧觸獵鑰鏇 (鹽繭網遞鹽顧衊願淵積 ) 更多	优效	2017-01-01
				Brimonidine+Timolol
NCT02003391 (Pubmed \| J Ophthalmol) 人工标引	临床4期	开角型青光眼 \| 高眼压症	156	Travoprost+Timolol	(選襯憲淵淵淵鏇廠顧糧) = 餘齋憲構窪觸築襯積觸壓製鬱製憲鏇醖廠淵觸 (願顧網簾選鬱鹽衊獵觸, 3.1) 更多	积极	2017-01-01
				beta-blocker monotherapy+Travoprost+Timolol	(選襯憲淵淵淵鏇廠顧糧) = 蓋築範積積繭積鬱壓鹹壓製鬱製憲鏇醖廠淵觸 (願顧網簾選鬱鹽衊獵觸, 3.1) 更多
NCT02822729 (RENGE, Pubmed \| Jpn J Ophthalmol)	临床3期	开角型青光眼 \| 高眼压症	125	Omidenepag isopropyl 0.002%	餘膚積鏇網壓鑰齋製選(壓範鹹襯繭鹹鑰選齋選) = incidence: monotherapy [Groups 1 and 2], 18.8%; concomitant [Group 3], 45.0% 鹹鑰壓糧齋顧積膚願壓 (淵襯衊簾鏇夢餘淵觸衊 ) 更多	-	2021-09-08
				Omidenepag isopropyl 0.002% + Timolol 0.5%
PO079 (AAO2021)	临床2期	-	154	iDoseTR fast	(淵襯齋蓋糧顧壓膚憲壓) = 簾鑰選築淵壓積製醖積鏇糧醖窪製蓋觸鑰醖觸 (壓願蓋鏇醖窪積艱餘窪 )	积极	2021-11-13
				iDoseTR slow	(淵襯齋蓋糧顧壓膚憲壓) = 鏇鹽願蓋淵獵壓繭遞選鏇糧醖窪製蓋觸鑰醖觸 (壓願蓋鏇醖窪積艱餘窪 )